Contrast-Induced Nephropathy: Evaluation of Preventive Strategies Based on Serum Creatinine and Cystatin C in Patients with Moderate to Severe Chronic Kidney Disease – A Randomized Clinical Trial

Contrast-Induced Nephropathy: Evaluation of Preventive Strategies Based on Serum Creatinine and Cystatin C in Patients with Moderate to Severe Chronic Kidney Disease – A Randomized Clinical Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Contrast-Induced Nephropathy: Evaluation of Preventive Strategies Based on Serum Creatinine and Cystatin C in Patients with Moderate to Severe Chronic Kidney Disease – A Randomized Clinical Trial Daniel Cesar Fernandes, Roberto Gomide, Thais Magalhaes, Rosa Tanmirys Lima, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6387719/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Contrast-induced acute kidney injury (CI-AKI) remains a clinically relevant complication, with uncertainties regarding its true epidemiology, pathophysiology, optimal diagnostic methods, and preventive strategies. As the global volume of contrast-enhanced imaging procedures continues to rise, there is a critical need to refine early detection and prevention approaches. Methods This prospective, randomized clinical trial included patients with peripheral artery disease requiring contrast-enhanced diagnostic and/or therapeutic procedures at a public hospital from February 2022 to March 2024. Patients were stratified into three groups based on their estimated glomerular filtration rate (eGFR): control group (eGFR > 60 mL/min/1.73m²), Group 1 (eGFR < 30 mL/min/1.73m²), and Group 2 (eGFR 30–59 mL/min/1.73m²). Within each group, patients were randomized into either a standard hydration protocol ( 1 mL/kg/h for 12 hours before and 12 hours after the procedure ) or an intervention protocol , which included atorvastatin (80 mg 12 hours before and 40 mg after the procedure) and oral N-acetylcysteine (600 mg every 12 hours, starting 24 hours before and continuing for 24 hours after the procedure), in addition to intravenous isotonic saline hydration. Serum creatinine (sCr) and cystatin C (sCys C) levels were measured at baseline, 24h, and 72h post-procedure. Results A total of 76 patients were included: 45 in the control group, 23 in Group 2, and 8 in Group 3 . There were no significant differences in baseline clinical or demographic characteristics between groups. Although numerically more CI-AKI cases were identified using sCys C, it did not demonstrate statistically significant superiority over sCr as a diagnostic biomarker (Kappa = 0.07, p = 0.554). In the control group , logistic regression analysis showed that the intervention was associated with a lower incidence of CI-AKI when sCys C was used as the diagnostic criterion (OR 0.81; 95% CI, 0.65–0.98; p = 0.025). However, this effect was not statistically significant in patients with impaired renal function. Factorial ANOVA and dispersion analysis did not confirm a significant effect of the intervention across groups or its interaction with renal function status when evaluating variations in both sCys C and sCr (p > 0.05). Conclusions When using sCys C as a diagnostic criterion, the combination of high-dose atorvastatin and N-acetylcysteine demonstrated a protective effect against CI-AKI in patients with normal renal function . However, this benefit was not observed in patients with moderate or severe chronic kidney disease, regardless of the biomarker used (sCr or sCys C). Furthermore, despite identifying more CI-AKI cases, sCys C did not exhibit statistically significant superiority over sCr for early CI-AKI diagnosis. Health sciences/Biomarkers Health sciences/Cardiology Health sciences/Medical research Health sciences/Nephrology Cystatin C Creatinine Contrast-induced nephropathy Chronic kidney disease Preventive strategies Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Contrast-induced acute kidney injury (CI-AKI) is an acute decline in renal function following exposure to iodinated contrast media (CM) during diagnostic and interventional procedures.( 1 ) It is one of the most common causes of in-hospital acute kidney injury, particularly among patients with chronic kidney disease (CKD), leading to increased morbidity, mortality, and healthcare costs.( 2 ) Despite advancements in contrast agents and preventive strategies, the true incidence and risk of CI-AKI remain controversial, partly due to variations in diagnostic criteria and biomarker sensitivity.( 3 ) Traditionally, CI-AKI has been defined by an increase in serum creatinine (sCr) ≥ 0.5 mg/dL or ≥ 25% from baseline within 2–5 days after contrast exposure.( 4 ) More recently, the Kidney Disease Improving Global Outcomes (KDIGO) proposed a more sensitive criterion: an increase of ≥ 0.3 mg/dL within 48 hours or ≥ 1.5 times the baseline within 7 days.( 5 ) However, serum creatinine has limitations as a biomarker due to its delayed elevation, leading to interest in cystatin C (sCys C) as a potentially earlier and more sensitive marker for CI-AKI detection.( 6 ) Given the high clinical impact of CI-AKI, particularly in patients with CKD, it is crucial to refine diagnostic methods and evaluate preventive strategies. It has been suggested that statins may reduce the CIAKI risk because they have beneficial effects on endothelial function, maintain nitric oxide production, and reduce oxidative stress.( 7 ) This study aimed to compare the diagnostic performance of sCys C versus sCr in detecting CI-AKI and to assess the efficacy of high-dose atorvastatin plus N-acetylcysteine (NAC) in preventing CI-AKI across different CKD stages. Methods Patient and Public Involvement This research was conducted in a public hospital setting, addressing a clinically relevant issue for patients with peripheral artery disease undergoing contrast-enhanced procedures. The findings will be disseminated through peer-reviewed publications and presentations at medical conferences, ensuring that healthcare professionals and stakeholders can apply the results to improve patient care and preventive strategies for contrast-induced acute kidney injury. Study Design and Setting This study was a prospective, single-blind, randomized clinical trial conducted at the Vascular Surgery Department of a public hospital in Goiânia, Brazil (Hospital Geral de Goiânia “Dr. Alberto Rassi”) between February 2022 and March 2024 . The study included patients with peripheral arterial disease (PAD) undergoing contrast-enhanced diagnostic and/or therapeutic procedures in the hospital’s hemodynamics unit (angiography and/or percutaneous interventions). The study protocol was approved by the hospital's Ethics Committee and the Goiás State Health Department (Approval Number: 5.307.711 ). It was also registered in the Brazilian Clinical Trials Registry (ReBEC) under U1111-1277-3145 (Universal Trial Number, WHO International Clinical Trials Registry Platform) . All participants provided written informed consent before enrollment. Inclusion and Exclusion Criteria Inclusion Criteria Age ≥18 years. Diagnosed with peripheral arterial disease (PAD) requiring contrast-enhanced procedures. Signed informed consent form . Exclusion Criteria Acute kidney injury. End-stage renal disease requiring dialysis. Congestive heart failure. Septic or cardiogenic shock. Use of nephrotoxic drugs or iodinated contrast in the past 72 hours. Randomization and Study Groups Patients were stratified based on their baseline renal function , using eGFR calculated by the CKD-EPI 2021 equation (creatinine-based) and CKD-EPI 2012 equation (cystatin C-based) . Patients were then randomized into two intervention groups using a stratified block randomization method with Microsoft Excel’s RAND () function . Three groups were defined based on renal function: Control group : eGFR >60 mL/min/1.73 m² (normal renal function). Group 1 : eGFR <30 mL/min/1.73 m² (end-stage renal disease or terminal). Group 2 : eGFR 30-59 mL/min/1.73 m² (moderate CKD or intermediate). Within each group, patients were randomly assigned (1:1) to either: Control (standard hydration only) : Intravenous 0.9% isotonic saline at 1 mL/kg/h , 12 hours before and 12 hours after the procedure. Intervention (high-dose atorvastatin + N-acetylcysteine + hydration) : Same hydration protocol as the control group. N-acetylcysteine (NAC) : 600 mg orally every 12 hours , starting 24 hours before and continuing 24 hours after the procedure. Atorvastatin : 80 mg 12 hours before and 40 mg 12 hours after the procedure. Contrast Agent and Biomarker Assessment All patients received low-osmolar, nonionic contrast media (Iohexol, Omnipaque 300 mg I/mL, GE Healthcare®) . Serum biomarkers were measured at the following time points: Serum creatinine (sCr) : Baseline (24 hours before), 24 hours, and 72 hours after the procedure. Method : Colorimetric kinetic assay ( Bioclin® kit ). Serum cystatin C (sCys C) : Baseline (24 hours before) and 24 hours after the procedure. Method : Turbidimetric immunoassay ( DB Diagnósticos do Brasil® kit ). Sample Size Calculation The sample size was determined using G*Power 3.1 software , assuming: Significance level (α) = 0.05 (95% confidence interval). Power (1-β) = 80% . Expected effect size (d) = 0.5 , based on previous studies. The estimated minimum sample size was 52 patients . To account for potential losses (15%) , the final sample size was 60 patients . Statistical Analysis Baseline characteristics were compared using t-tests (continuous variables) and chi-square tests (categorical variables) . The primary outcome (CI-AKI incidence) was analyzed using logistic regression with odds ratios (OR) and 95% confidence intervals (CI) . Repeated measures ANOVA was used to evaluate biomarker variations over time. p-values <0.05 were considered statistically significant . Analyses were performed using SPSS 26.0 (IBM Corp.) . Primary Outcome and Statistical Analysis Primary Outcome The primary outcome was the incidence of contrast-induced acute kidney injury (CI-AKI) , evaluated using two distinct criteria based on serum creatinine (sCr) and serum cystatin C (sCys C) levels . Serum Creatinine-Based CI-AKI Definition Absolute increase in sCr ≥0.5 mg/dL and/or Relative increase of ≥25% from baseline , measured 72 hours post-procedure . Serum Cystatin C-Based CI-AKI Definition Increase of ≥10% in sCys C 24 hours after contrast exposure . This threshold has been well established in previous studies as an independent risk factor for CI-AKI. Statistical Analysis All collected data were recorded in a Microsoft Excel® spreadsheet and analyzed using IBM SPSS Statistics v26.0 (IBM Corp., Armonk, USA) . Descriptive statistics : Continuous variables : Presented as means and standard deviations . Categorical variables : Presented as absolute and relative frequencies (percentages). Comparisons between groups : Chi-square test for categorical variables. t-tests or Mann-Whitney U tests for continuous variables, depending on normality distribution. Inferential statistics : Logistic regression analysis was performed to assess the association between the intervention and CI-AKI incidence. Repeated-measures ANOVA was used to evaluate biomarker variations over time. Significance threshold : A p-value <0.05 was considered statistically significant . Results Baseline Characteristics The study enrolled a total of 76 patients , stratified into three renal function groups : Control (normal renal function), Group 2 (moderate CKD or intermediate), and Group 1 (end-stage renal disease or terminal) . Patients were further subdivided based on intervention (high-dose atorvastatin + N-acetylcysteine) or standard hydration alone . Baseline demographic and clinical characteristics, including age, sex, ethnicity, comorbidities (hypertension, diabetes, dyslipidemia), and lifestyle factors , were homogeneously distributed across groups (Table 1). Pearson’s chi-square test indicated no statistically significant differences between groups, ensuring that subsequent analyses were not confounded by baseline imbalances. Incidence of CI-AKI Based on Serum Creatinine and Cystatin C Serum Creatinine-Based Diagnosis Logistic regression analysis did not show a significant effect of the intervention on CI-AKI incidence in patients with normal renal function (Control Group) . No cases of CI-AKI were detected in Groups 1 (end-stage CKD) and 2 (moderate CKD) using serum creatinine (sCr) criteria , preventing statistical assessment of the intervention’s impact in these patients (Table 2). Serum Cystatin C-Based Diagnosis When CI-AKI was assessed using serum cystatin C (sCys C) criteria , the intervention demonstrated a protective effect in the Control Group , but not in Groups 1 and 2 (Table 3). Additionally, more CI-AKI cases were diagnosed using sCys C than sCr , suggesting greater sensitivity of this biomarker . Impact of Prior Statin Use on CI-AKI Risk In patients without prior statin use , the odds ratio (OR) <1 suggested a possible reduction in CI-AKI risk with the intervention . However, a wide confidence interval and a non-significant p-value indicated a lack of statistical significance (Table 4). Among patients with prior statin use , no CI-AKI cases were detected using sCr , preventing statistical evaluation of the intervention’s effect. When using sCys C , a non-significant trend toward renal protection was observed in patients with and without prior statin use (Table 5). Association Between Contrast Volume and CI-AKI Scatter plot analyses revealed: No significant correlation between contrast volume and sCr variation in patients without intervention , including those in Group 1 (end-stage CKD), despite a strong positive trend (p = 0.09) (Figure 1). sCys C levels remained stable or declined in Groups Control and 2 , suggesting that the intervention did not impair renal function and may have provided a stabilizing effect . In Group 1 (end-stage CKD), sCys C increased with contrast volume despite intervention , indicating a partial failure of nephroprotection in this subgroup (Figure 2). Effect of Intervention on Biomarker Variability Factorial ANOVA Analysis sCr variation differed significantly between groups ( p = 0.01 ), indicating renal function-dependent biomarker changes . The intervention had no significant overall effect on sCr variation ( p = 0.90 ), as reflected by similar trends across intervention and non-intervention groups. No significant interaction between group and intervention was found ( p = 0.86 ), suggesting that the intervention's impact did not differ across renal function categories. sCys C variation was highest in end-stage CKD patients but showed high inter-individual variability , limiting statistical significance. Individual Statistical Tests for Biomarker Comparisons Student’s t-test and Mann-Whitney U test were used to compare intervention effects on serum creatinine (ΔCr) and serum cystatin C (ΔC) . Control Group : Intervention significantly reduced sCr ( p = 0.027, t-test; p = 0.045, Mann-Whitney ). sCys C reduction was not statistically significant ( p = 0.127, t-test; p = 0.062, Mann-Whitney ). End-Stage CKD (Group 1) : sCys C showed a significant protective effect ( p = 0.020, t-test; p = 0.016, Mann-Whitney ). sCr showed no significant trend ( p = 0.118, t-test; p = 0.111, Mann-Whitney ). Thus, sCys C detected a significant nephroprotective effect in end-stage CKD patients, whereas sCr did not , whereas in patients with normal renal function, sCr was more responsive to the intervention than sCys C . Correlation Between Biomarkers: Creatinine vs. Cystatin C Scatter plot analysis of sCr and sCys C correlation revealed: No statistically significant correlation between biomarkers in non-intervention groups . In end-stage CKD (Group 1), sCys C and sCr exhibited a strong negative correlation , suggesting that sCr may not accurately reflect early renal dysfunction . With intervention, this correlation was reversed (-0.81 to 0.05), implying that the intervention altered the relationship between biomarkers . Summary of biomarker trends: Without intervention : No clear correlation in Control and Group 2; strong negative correlation in Group 1 , indicating that sCr may underdiagnose renal dysfunction . With intervention : Biomarker correlation became weak or neutral , suggesting that the intervention may have equalized their diagnostic performance . Diagnostic Agreement Between Biomarkers (Kappa Test) A Kappa concordance test was performed to evaluate agreement between sCr-based and sCys C-based CI-AKI diagnoses (Table 6). Low Kappa coefficient (K = 0.07, non-significant p-value) indicated poor agreement between the two biomarkers . No patient was simultaneously classified as "CI-AKI positive" by both biomarkers . Seven patients were diagnosed with CI-AKI by sCys C but not by sCr , suggesting potential underdiagnosis by sCr . Thus, sCys C may detect renal dysfunction earlier than sCr , reinforcing its potential as a more sensitive biomarker for CI-AKI . Discussion Main Findings This study demonstrated that the incidence of CI-AKI was higher when using serum cystatin C (sCys C) criteria compared to serum creatinine (sCr) , suggesting that sCys C may be a more sensitive biomarker for detecting contrast-induced renal dysfunction. sCys C is recognized as a functional biomarker of glomerular filtration rate (GFR) with greater sensitivity than sCr, as it is not secreted by renal tubules and reaches its peak concentration within 24 hours post-contrast exposure , enabling the detection of subtle GFR changes.( 8 , 9 ) Briguori et al. demonstrated that a ≥ 10% increase in sCys C within 24 hours of contrast exposure was associated with a concurrent increase of ≥ 0.3 mg/dL in sCr and was an independent risk factor for mortality and dialysis at one year .( 10 ) Despite sCr being the most widely used biomarker for renal function assessment , its delayed kinetics (24-72h post-exposure, peaking at 3–5 days, and normalizing in 10–14 days) limits its utility for early CI-AKI detection . Additionally, sCr remains within the reference range until approximately 50% of renal function is lost , reducing its sensitivity( 8 ). Comparison with Previous Studies A potential explanation for the low detection of CI-AKI using sCr in this study is that the historical definition of CI-AKI (Mehran et al., 2004) was used ( 11 ), rather than the current KDIGO definition , which has been widely accepted by the nephrology community. This discrepancy may have influenced the agreement analysis between biomarkers , differing from the findings of Fu et al., who reported a strong correlation between sCys C and sCr in CI-AKI diagnosis (95% sensitivity and 79% specificity). ( 12 , 13 ) Our statistical analysis, employing more robust methodologies, did not demonstrate agreement between sCr and sCys C variations , suggesting that these biomarkers may be reflecting different stages of renal dysfunction rather than diagnosing the same phenomenon. Nevertheless, an important finding of this study is that in the control group, CI-AKI (based on sCys C criteria) was significantly reduced with high-dose atorvastatin + N-acetylcysteine (NAC) intervention , supporting a potential nephroprotective effect of this strategy. Effect of Prior Statin Use In dyslipidemic patients without prior statin use , the intervention did not significantly modify CI-AKI risk when assessed by sCr levels ( OR close to 1, p > 0.05 ). Among patients with prior statin use , no CI-AKI cases were detected using sCr , making statistical assessment infeasible. These findings raise the possibility that patients on chronic statin therapy may have been preconditioned against CI-AKI development . However, when using sCys C as a biomarker , the intervention did not significantly impact CI-AKI incidence, regardless of prior statin use. While the odds ratio was < 1 , suggesting a potential renoprotective trend , this effect did not reach statistical significance. These results contrast with Quintavalle et al. and meta-analyses reporting a protective effect of high-dose atorvastatin (80 mg) in patients with impaired renal function undergoing contrast-enhanced procedures. ( 14 , 15 ) Further studies are needed to clarify the role of statins in CI-AKI prevention, particularly regarding biomarker-dependent differences in diagnostic sensitivity. Contrast Volume and Renal Function Assessing the influence of contrast volume on renal function, no statistically significant correlation was found between contrast volume and sCr variations in non-intervention patients across different renal function strata. However, in patients with intervention (particularly Group 1 - end-stage CKD), a strong positive correlation was observed , suggesting a potential association between contrast volume and sCr variation . Although this trend did not reach statistical significance ( p = 0.09 ), it indicates that higher contrast exposure may contribute to renal injury in this subgroup . When assessing sCys C variation , contrast volume did not show a clear or consistent relationship with renal function , independent of intervention. This supports the idea that sCys C may be less influenced by contrast volume than sCr , reinforcing its potential utility as an early biomarker for renal dysfunction . These findings align with Mehran et al. and Maioli et al., who identified an increased CI-AKI risk only with contrast volumes exceeding 350 mL or 4 mL/kg. Clinical Implications These findings have important implications for clinical practice , especially given the global rise in contrast-enhanced procedures . Despite advancements in CI-AKI understanding, many aspects of its pathophysiology, early diagnosis, and prevention remain incompletely elucidated . Even with methodologically rigorous studies , significant discrepancies persist regarding preventive strategies and biomarker-based early detection of CI-AKI . Study Limitations Several limitations should be considered: Small sample size , which may limit statistical power. Use of historical CI-AKI criteria (Mehran et al., 2004) instead of the more widely accepted KDIGO definition . Potential confounding effects of NAC combined with atorvastatin . While NAC use in CI-AKI prevention remains controversial, a large-scale study demonstrated its lack of efficacy in this context.( 11 , 16 , 17 ) Future Directions Future research should focus on: Improving CI-AKI pathophysiological understanding . Developing more sensitive and specific early diagnostic methods . Identifying pharmacological strategies with proven efficacy in preventing CI-AKI, particularly in high-risk CKD patients. Given its clinical relevance , CI-AKI remains a major challenge for nephrologists and interventionalists, necessitating ongoing research efforts to optimize its diagnosis, prevention, and management . Conclusion In this randomized clinical trial , serum creatinine (sCr) and cystatin C (sCys C) did not demonstrate consistent correlation in the diagnosis of contrast-induced acute kidney injury (CI-AKI) . This finding suggests that these biomarkers may reflect different aspects of renal function or that one may lack sufficient sensitivity for detecting this specific type of renal injury. The administration of high-dose statins combined with N-acetylcysteine (NAC) significantly reduced CI-AKI incidence in patients with preserved renal function , when assessed using sCys C criteria . However, this nephroprotective effect was not observed in patients with moderate to severe chronic kidney disease , regardless of the biomarker used ( sCr or sCys C ). Moreover, in patients with and without prior statin use , the combination of high-dose statins and NAC did not significantly impact CI-AKI incidence , whether evaluated by sCr or sCys C levels . Additionally, the contrast volume used during procedures did not influence CI-AKI incidence , irrespective of the biomarker employed for detection. Clinical Implications and Future Perspectives Optimizing CI-AKI detection and prevention in contrast-enhanced procedures requires a multifactorial approach , considering: - Baseline renal function ; - Selection of the most appropriate biomarker ; - Refinement of diagnostic criteria . The introduction of novel renal injury biomarkers may represent a significant advancement , enabling earlier detection and more effective preventive strategies for CI-AKI. Declarations Disclosures : All authors report no relationships that could be construed as a conflict of interest. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Funding: This study was self-funded by the author(s), and no external financial support was received. Universal Trial Number, WHO International Clinical Trials Registry Platform: U1111-1277-3145 Ethics approval and consent to participate The study protocol was approved by the hospital's Ethics Committee and the Goiás State Health Department (Approval Number: 5.307.711) Consent for publication Not applicable Availability of data and material The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request Competing interests All authors report no relationships that could be construed as a conflict of interest. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation Funding This study was entirely funded by the corresponding author with personal resources Authors' contributions DCMF wrote the main manuscript, design of the work; the acquisition, analysis and interpretation of data RG analysis and interpretation of data. TM acquisition, analysis and interpretation of data RTL acquisition, analysis and interpretation of data RMS acquisition, analysis and interpretation of data PRM acquisition, analysis, interpretation of data and prepared figures AR acquisition, analysis and interpretation of data DVN prepare figure and tables MLA acquisition, analysis and interpretation of data LP acquisition, analysis and interpretation of data MB acquisition, analysis , interpretation of data and revised manuscript MLS acquisition, analysis , interpretation of data and revised manuscript Acknowledgements The author would like to thank the entire Vascular Surgery team and the biochemists from the General Hospital of Goiânia for their valuable contributions. Special thanks also go to the INGOH Laboratory in Goiânia. All of them were essential for the execution of this study. References Azzalini, L. & Kalra, S. Contrast-Induced Acute Kidney Injury-Definitions, Epidemiology, and Implications. Interv Cardiol. Clin. 9 (3), 299–309 (2020). Nash, K., Hafeez, A. & Hou, S. Hospital-acquired renal insufficiency. Am. J. Kidney Dis. Off J. Natl. Kidney Found. 39 (5), 930–936 (2002). Morcos, S. K. Prevention of contrast media-induced nephrotoxicity after angiographic procedures. J. Vasc Interv Radiol. JVIR . 16 (1), 13–23 (2005). Scharnweber, T., Alhilali, L. & Fakhran, S. Contrast-Induced Acute Kidney Injury: Pathophysiology, Manifestations, Prevention, and Management. Magn. Reson. Imaging Clin. N Am. 25 (4), 743–753 (2017). Yang, J. S. et al. The molecular mechanism of contrast-induced nephropathy (CIN) and its link to in vitro studies on iodinated contrast media (CM). BioMedicine 8 (1), 1 (2018). Eng, J. et al. Comparative Effect of Contrast Media Type on the Incidence of Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis. Ann. Intern. Med. 164 (6), 417–424 (2016). Barbieri, L. et al. The role of statins in the prevention of contrast induced nephropathy: a meta-analysis of 8 randomized trials. J. Thromb. Thrombolysis . 38 (4), 493–502 (2014). D’Amore, C., Nuzzo, S. & Briguori, C. Biomarkers of Contrast-Induced Nephropathy:: Which Ones are Clinically Important? Interv Cardiol. Clin. 9 (3), 335–344 (2020). Kuwabara, T. et al. Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. Kidney Int. 75 (3), 285–294 (2009). Briguori, C. et al. Cystatin C and contrast-induced acute kidney injury. Circulation 121 (19), 2117–2122 (2010). Mehran, R. et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J. Am. Coll. Cardiol. 44 (7), 1393–1399 (2004). Fu, N., Liang, M. & Yang, S. High Loading Dose of Atorvastatin for the Prevention of Serum Creatinine and Cystatin C-Based Contrast-Induced Nephropathy Following Percutaneous Coronary Intervention. Angiology 69 (8), 692–699 (2018). Alharazy, S. M. et al. Serum neutrophil gelatinase-associated lipocalin and cystatin C are early biomarkers of contrast-induced nephropathy after coronary angiography in patients with chronic kidney disease. Angiology 65 (5), 436–442 (2014). Quintavalle, C. et al. Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury. Circulation 126 (25), 3008–3016 (2012). Cheungpasitporn, W. et al. Periprocedural effects of statins on the incidence of contrast-induced acute kidney injury: a systematic review and meta-analysis of randomized controlled trials. Ren. Fail. 37 (4), 664–671 (2015). Weisbord, S. D. et al. Prevention of contrast-induced AKI: a review of published trials and the design of the prevention of serious adverse events following angiography (PRESERVE) trial. Clin. J. Am. Soc. Nephrol. CJASN . 8 (9), 1618–1631 (2013). Maioli, M. et al. Preprocedural score for risk of contrast-induced nephropathy in elective coronary angiography and intervention. J. Cardiovasc. Med. Hagerstown Md. 11 (6), 444–449 (2010). Tables Table 1 Characterization of the patient profile according to groups and intervention Whithout Intervenction p* Whith Intervention p* n (%) Normal Intermediate Terminal Normal Intermediate Terminal Age Group 31 a 59 anos 4 (19,0) 0 (0,0) 2 (66,7) 0,203 8 (33,3) 0 (0,0) 1 (20,0) 0,074 60 ou mais 17 (81,0) 11 (100,0) 1 (33,3) 16 (66,7) 12 (100,0) 4 (80,0) Gender Female 5 (23,8) 1 ( 9 , 1 ) 1 (33,3) 0,511 12 (50,0) 4 (33,3) 1 (20,0) 0,369 Male 16 (76,2) 10 (90,9) 2 (66,7) 12 (50,0) 8 (66,7) 4 (80,0) Race White 10 (47,6) 5 (45,5) 1 (33,3) 0,657 15 (62,5) 5 (41,7) 2 (40,0) 0,286 Black 1 ( 4 , 8 ) 2 (18,2) 0 (0,0) 1 ( 4 , 2 ) 0 (0,0) 1 (20,0) Mixed 10 (47,6) 4 (36,4) 2 (66,7) 8 (33,3) 7 (58,3) 2 (40,0) Hypertension No 10 (47,6) 3 (27,3) 0 (0,0) 0,200 7 (29,2) 2 ( 16 , 7 ) 0 (0,0) 0,312 Yes 11 (52,4) 8 (72,7) 3 (100,0) 17 (70,8) 10 (83,3) 5 (100,0) Diabete No 12 (57,1) 10 (90,9) 2 (66,7) 0,148 12 (50,0) 8 (66,7) 3 (60,0) 0,626 Yes 9 (42,9) 1 ( 9 , 1 ) 1 (33,3) 12 (50,0) 4 (33,3) 2 (40,0) Dyslipidemia No 17 (81,0) 8 (72,7) 2 (66,7) 0,782 21 (87,5) 10 (83,3) 4 (80,0) 0,886 Yes 4 (19,0) 3 (27,3) 1 (33,3) 3 ( 12 , 5 ) 2 ( 16 , 7 ) 1 (20,0) Smoker No 7 (33,3) 4 (36,4) 1 (33,3) 0,986 9 (37,5) 2 ( 16 , 7 ) 2 (40,0) 0,410 Yes 14 (66,7) 7 (63,6) 2 (66,7) 15 (62,5) 10 (83,3) 3 (60,0) Procedure Performed Angioplasty 5 (23,8) 1 ( 9 , 1 ) 0 (0,0) 0,433 5 (20,8) 2 ( 16 , 7 ) 1 (20,0) 0,683 Aortography 1 ( 4 , 8 ) 1 ( 9 , 1 ) 1 (33,3) 5 (20,8) 2 ( 16 , 7 ) 0 (0,0) Arteriography 15 (71,4) 9 (81,8) 2 (66,7) 14 (58,3) 8 (66,7) 4 (80,0) n, absolute frequency; %, relative frequency. Table 2 Association of renal injury (Cr) prevalence among patients with and without intervention according to renal function groups. Renal Function Renal Injury Odds Ratio(OR) IC 95% p* No Yes Normal Without intervention 19 (46,3) 2 (50,0) 0,86 (0,66 − 6,73) 0,889 With intervention 22 (53,7) 2 (50,0) Intermediate Without intervention 11 (47,8) 0 (0,0) na na With intervention 12 (52,2) 0 (0,0) Terminal Without intervention 3 (37,5) 0 (0,0) na na With intervention 5 (62,5) 0 (0,0) * Note : Simple logistic regression; NA, not applicable; n, absolute frequency; %, relative frequency. Table 3 Association of renal injury (C) prevalence among patients with and without intervention according to renal function groups. Renal Function Renal Injury Odds Ratio(OR) IC 95% p* No Yes Normal Without intervention 17 (41,5) 4 (100,0) 0,81 (0,65 − 0,98) 0,025 With intervention 24 (58,5) 0 (0,0) Intermediate Without intervention 10 (47,6) 1 (50,0) 0,90 (0,05 − 1,65) 0,942 With intervention 11 (52,4) 1 (50,0) Terminal Without intervention 3 (42,9) 0 (0,0) 1,25 (0,81 − 1,93) 0,408 With intervention 4 (57,1) 1 (100,0) * Note : Simple logistic regression; NA, not applicable; n, absolute frequency; %, relative frequency. Table 4 Association of renal injury incidence (ΔCr) among patients with and without intervention according to prior statin use. Prior Statin Use Renal Injury Odds Ratio (OR) IC 95% p* No Yes No prior statin use Without intervention 25 (43,1) 2 (50,0) 0,75 (0,15 − 5,75) 0,788 With intervention 33 (56,9) 2 (50,0) Prior statin use Without intervention 8 (57,1) 0 (0,0) na na With intervention 6 (42,9) 0 (0,0) Note: Simple logistic regression; NA, not applicable; n, absolute frequency; %, relative frequency. Table 5 Association of renal injury incidence (ΔC) among patients with and without intervention according to prior statin use. Prior Statin Use Renal Injury Odds Ratio (OR) IC 95% p* No Yes No prior statin use Without intervention 23 (41,1) 4 (66,7) 0,34 (0,06 − 2,06) 0,221 With intervention 33 (58,9) 2 (33,3) Prior statin use Without intervention 7 (53,8) 1 (100,0) 0,31 (0,05 − 1,69) 0,369 With intervention 6 (46,2) 0 (0,0) Note : Simple logistic regression; NA, not applicable; n, absolute frequency; %, relative frequency. Table 6 Concordance analysis between renal injury by C and Cr. Cr Kappa p C No Yes Total No 65 (90,3) 4 (100,0) 69 Yes 7 ( 9 , 7 ) 0 (0,0) 7 0,07 0,554 Total 72 4 76 Note : Kappa; n, absolute frequency; % relative frequency. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6387719","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":439076575,"identity":"6e796293-7e3c-43d1-83b2-9766425b2ef7","order_by":0,"name":"Daniel Cesar Fernandes","email":"data:image/png;base64,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","orcid":"","institution":"General Hospital Of Goiania","correspondingAuthor":true,"prefix":"","firstName":"Daniel","middleName":"Cesar","lastName":"Fernandes","suffix":""},{"id":439076577,"identity":"420aa69d-c081-4544-ac13-a9d87f0d251a","order_by":1,"name":"Roberto Gomide","email":"","orcid":"","institution":"General Hospital Of Goiania","correspondingAuthor":false,"prefix":"","firstName":"Roberto","middleName":"","lastName":"Gomide","suffix":""},{"id":439076580,"identity":"d7b6afef-6c4a-4df8-92e0-50e58fdf1819","order_by":2,"name":"Thais Magalhaes","email":"","orcid":"","institution":"General Hospital Of Goiania","correspondingAuthor":false,"prefix":"","firstName":"Thais","middleName":"","lastName":"Magalhaes","suffix":""},{"id":439076582,"identity":"504996a0-6f16-4ca3-b065-b697dc21271e","order_by":3,"name":"Rosa Tanmirys Lima","email":"","orcid":"","institution":"General Hospital Of Goiania","correspondingAuthor":false,"prefix":"","firstName":"Rosa","middleName":"Tanmirys","lastName":"Lima","suffix":""},{"id":439076585,"identity":"2a2a9c22-c245-487b-830b-4c2e4770fd74","order_by":4,"name":"Romulo Mendes Silva","email":"","orcid":"","institution":"General Hospital Of Goiania","correspondingAuthor":false,"prefix":"","firstName":"Romulo","middleName":"Mendes","lastName":"Silva","suffix":""},{"id":439076587,"identity":"7c41f63a-a85b-45ec-b352-b397b6632729","order_by":5,"name":"Paulo Ricardo Moreira","email":"","orcid":"","institution":"General Hospital Of Goiania","correspondingAuthor":false,"prefix":"","firstName":"Paulo","middleName":"Ricardo","lastName":"Moreira","suffix":""},{"id":439076588,"identity":"3fa16ba1-7dcc-4648-864d-06031687d8d7","order_by":6,"name":"Alef Ribeiro","email":"","orcid":"","institution":"General Hospital Of Goiania","correspondingAuthor":false,"prefix":"","firstName":"Alef","middleName":"","lastName":"Ribeiro","suffix":""},{"id":439076589,"identity":"37240a9f-91c0-4214-8b55-552e39be77ad","order_by":7,"name":"Delvo Vasques Netto","email":"","orcid":"","institution":"General Hospital Of Goiania","correspondingAuthor":false,"prefix":"","firstName":"Delvo","middleName":"Vasques","lastName":"Netto","suffix":""},{"id":439076590,"identity":"5f295b5a-1f46-4cb3-a668-70c03928ff91","order_by":8,"name":"Maria Luiza Amaral","email":"","orcid":"","institution":"General Hospital Of Goiania","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Luiza","lastName":"Amaral","suffix":""},{"id":439076592,"identity":"cfd9b9cd-36cf-461d-a8e3-0653a80c9b28","order_by":9,"name":"Lorrayne Pequeno","email":"","orcid":"","institution":"General Hospital Of Goiania","correspondingAuthor":false,"prefix":"","firstName":"Lorrayne","middleName":"","lastName":"Pequeno","suffix":""},{"id":439076593,"identity":"8e5ef8a5-af53-4397-a078-61401c300258","order_by":10,"name":"Matheus Bertanha","email":"","orcid":"","institution":"São Paulo State University","correspondingAuthor":false,"prefix":"","firstName":"Matheus","middleName":"","lastName":"Bertanha","suffix":""},{"id":439076594,"identity":"3bf4eaf0-14b3-4b35-afcb-6a7c8e58005b","order_by":11,"name":"Marcone Lima Sobreira","email":"","orcid":"","institution":"São Paulo State University","correspondingAuthor":false,"prefix":"","firstName":"Marcone","middleName":"Lima","lastName":"Sobreira","suffix":""}],"badges":[],"createdAt":"2025-04-06 15:53:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6387719/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6387719/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80145590,"identity":"145fb193-ef1f-4424-ae36-01767713632c","added_by":"auto","created_at":"2025-04-08 12:24:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":100697,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScatter plot demonstrating the relationship between contrast amount and Cr variation according to group and intervention.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6387719/v1/5cdb3e3a956ae872cb6606e9.png"},{"id":80145588,"identity":"19c88dae-cae7-4858-9abb-ac266b3dd80e","added_by":"auto","created_at":"2025-04-08 12:24:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":96701,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScatter plot demonstrating the relationship between contrast amount and C variation according to group and intervention.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6387719/v1/52b93f93427fcddd85edb9f5.png"},{"id":80145964,"identity":"412142db-a0e7-45fe-b994-0abec9636f57","added_by":"auto","created_at":"2025-04-08 12:32:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":96371,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScatter plot demonstrating the correlation result between Cr delta and C according to group and intervention.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6387719/v1/9a196ed14ff6e759e1403b36.png"},{"id":80145963,"identity":"47bfc83c-0cea-4a3f-9381-2e0539132686","added_by":"auto","created_at":"2025-04-08 12:32:57","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":49371,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBar graph with a 95% confidence interval demonstrating the factorial ANOVA result for Cr variation as a function of groups and intervention.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6387719/v1/be6e107183299468fd5feeff.png"},{"id":80145592,"identity":"186530a3-5599-42e2-a3ab-53fd7c78889d","added_by":"auto","created_at":"2025-04-08 12:24:57","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":43900,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBar graph with a 95% confidence interval demonstrating the factorial ANOVA result for C variation as a function of groups and intervention.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6387719/v1/ba5835ebc76923dd97f52974.png"},{"id":84444400,"identity":"dec1d71c-f7f9-46e6-9fc2-e170b77907ef","added_by":"auto","created_at":"2025-06-12 05:02:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6368416,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6387719/v1/63193d62-ad74-4b80-8969-915d3be4b67d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Contrast-Induced Nephropathy: Evaluation of Preventive Strategies Based on Serum Creatinine and Cystatin C in Patients with Moderate to Severe Chronic Kidney Disease – A Randomized Clinical Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eContrast-induced acute kidney injury (CI-AKI) is an acute decline in renal function following exposure to iodinated contrast media (CM) during diagnostic and interventional procedures.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) It is one of the most common causes of in-hospital acute kidney injury, particularly among patients with chronic kidney disease (CKD), leading to increased morbidity, mortality, and healthcare costs.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Despite advancements in contrast agents and preventive strategies, the true incidence and risk of CI-AKI remain controversial, partly due to variations in diagnostic criteria and biomarker sensitivity.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eTraditionally, CI-AKI has been defined by an increase in serum creatinine (sCr)\u0026thinsp;\u0026ge;\u0026thinsp;0.5 mg/dL or \u0026ge;\u0026thinsp;25% from baseline within 2\u0026ndash;5 days after contrast exposure.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) More recently, the Kidney Disease Improving Global Outcomes (KDIGO) proposed a more sensitive criterion: an increase of \u0026ge;\u0026thinsp;0.3 mg/dL within 48 hours or \u0026ge;\u0026thinsp;1.5 times the baseline within 7 days.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) However, serum creatinine has limitations as a biomarker due to its delayed elevation, leading to interest in cystatin C (sCys C) as a potentially earlier and more sensitive marker for CI-AKI detection.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eGiven the high clinical impact of CI-AKI, particularly in patients with CKD, it is crucial to refine diagnostic methods and evaluate preventive strategies. It has been suggested that statins may reduce the CIAKI risk because they have beneficial effects on endothelial function, maintain nitric oxide production, and reduce oxidative stress.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) This study aimed to compare the diagnostic performance of sCys C versus sCr in detecting CI-AKI and to assess the efficacy of high-dose atorvastatin plus N-acetylcysteine (NAC) in preventing CI-AKI across different CKD stages.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003ePatient and Public Involvement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was conducted in a public hospital setting, addressing a clinically relevant issue for patients with peripheral artery disease undergoing contrast-enhanced procedures. The findings will be disseminated through peer-reviewed publications and presentations at medical conferences, ensuring that healthcare professionals and stakeholders can apply the results to improve patient care and preventive strategies for contrast-induced acute kidney injury.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design and Setting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was a \u003cstrong\u003eprospective, single-blind, randomized clinical trial\u003c/strong\u003e conducted at the \u003cstrong\u003eVascular Surgery Department of a public hospital in Goi\u0026acirc;nia, Brazil (Hospital Geral de Goi\u0026acirc;nia \u0026ldquo;Dr. Alberto Rassi\u0026rdquo;)\u003c/strong\u003e between \u003cstrong\u003eFebruary 2022 and March 2024\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e The study included patients with \u003cstrong\u003eperipheral arterial disease (PAD) undergoing contrast-enhanced diagnostic and/or therapeutic procedures\u003c/strong\u003e in the hospital\u0026rsquo;s hemodynamics unit (angiography and/or percutaneous interventions).\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the hospital\u0026apos;s \u003cstrong\u003eEthics Committee and the Goi\u0026aacute;s State Health Department\u003c/strong\u003e (Approval Number: \u003cstrong\u003e5.307.711\u003c/strong\u003e). It was also \u003cstrong\u003eregistered in the Brazilian Clinical Trials Registry (ReBEC)\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eunder\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eU1111-1277-3145 (Universal Trial Number, WHO International Clinical Trials Registry Platform)\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e All participants provided \u003cstrong\u003ewritten informed\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003econsent\u003c/strong\u003e before enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion and Exclusion Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eAge \u0026ge;18 years.\u003c/li\u003e\n \u003cli\u003eDiagnosed with \u003cstrong\u003eperipheral arterial disease (PAD)\u003c/strong\u003e requiring contrast-enhanced procedures.\u003c/li\u003e\n \u003cli\u003eSigned \u003cstrong\u003einformed consent form\u003c/strong\u003e.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eExclusion Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eAcute kidney injury.\u003c/li\u003e\n \u003cli\u003eEnd-stage renal disease requiring dialysis.\u003c/li\u003e\n \u003cli\u003eCongestive heart failure.\u003c/li\u003e\n \u003cli\u003eSeptic or cardiogenic shock.\u003c/li\u003e\n \u003cli\u003eUse of \u003cstrong\u003enephrotoxic drugs\u003c/strong\u003e or \u003cstrong\u003eiodinated contrast\u003c/strong\u003e in the past 72 hours.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eRandomization and Study Groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were stratified based on their \u003cstrong\u003ebaseline renal function\u003c/strong\u003e, using eGFR calculated by the \u003cstrong\u003eCKD-EPI 2021 equation (creatinine-based) and CKD-EPI 2012 equation (cystatin C-based)\u003c/strong\u003e. Patients were then randomized into two \u003cstrong\u003eintervention groups\u003c/strong\u003e using a \u003cstrong\u003estratified block randomization method\u003c/strong\u003e with \u003cstrong\u003eMicrosoft Excel\u0026rsquo;s RAND () function\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThree groups were defined based on renal function:\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eControl group\u003c/strong\u003e: eGFR \u003cstrong\u003e\u0026gt;60 mL/min/1.73 m\u0026sup2;\u003c/strong\u003e (normal renal function).\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eGroup 1\u003c/strong\u003e: eGFR \u003cstrong\u003e\u0026lt;30 mL/min/1.73 m\u0026sup2;\u003c/strong\u003e (end-stage renal disease or terminal).\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eGroup 2\u003c/strong\u003e: eGFR \u003cstrong\u003e30-59 mL/min/1.73 m\u0026sup2;\u003c/strong\u003e (moderate CKD or intermediate).\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWithin each group, patients were \u003cstrong\u003erandomly assigned\u003c/strong\u003e (1:1) to either:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003e\u003cstrong\u003eControl (standard hydration only)\u003c/strong\u003e:\u003cul type=\"circle\"\u003e\n \u003cli\u003eIntravenous \u003cstrong\u003e0.9% isotonic saline\u003c/strong\u003e at \u003cstrong\u003e1 mL/kg/h\u003c/strong\u003e, 12 hours before and 12 hours after the procedure.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eIntervention (high-dose atorvastatin + N-acetylcysteine + hydration)\u003c/strong\u003e:\u003cul type=\"circle\"\u003e\n \u003cli\u003e\u003cstrong\u003eSame hydration protocol\u003c/strong\u003e as the control group.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eN-acetylcysteine (NAC)\u003c/strong\u003e: \u003cstrong\u003e600 mg orally every 12 hours\u003c/strong\u003e, starting \u003cstrong\u003e24 hours before and continuing 24 hours after\u003c/strong\u003e the procedure.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eAtorvastatin\u003c/strong\u003e: \u003cstrong\u003e80 mg 12 hours before\u003c/strong\u003e and \u003cstrong\u003e40 mg 12 hours after\u003c/strong\u003e the procedure.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eContrast Agent and Biomarker Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients received \u003cstrong\u003elow-osmolar, nonionic contrast media (Iohexol, Omnipaque 300 mg I/mL, GE Healthcare\u0026reg;)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSerum biomarkers were measured at the following time points:\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eSerum creatinine (sCr)\u003c/strong\u003e:\u003cul type=\"circle\"\u003e\n \u003cli\u003e\u003cstrong\u003eBaseline (24 hours before), 24 hours, and 72 hours after\u003c/strong\u003e the procedure.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eMethod\u003c/strong\u003e: Colorimetric kinetic assay (\u003cstrong\u003eBioclin\u0026reg; kit\u003c/strong\u003e).\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSerum cystatin C (sCys C)\u003c/strong\u003e:\u003cul type=\"circle\"\u003e\n \u003cli\u003e\u003cstrong\u003eBaseline (24 hours before) and 24 hours after\u003c/strong\u003e the procedure.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eMethod\u003c/strong\u003e: Turbidimetric immunoassay (\u003cstrong\u003eDB Diagn\u0026oacute;sticos do Brasil\u0026reg; kit\u003c/strong\u003e).\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eSample Size Calculation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe sample size was determined using \u003cstrong\u003eG*Power 3.1 software\u003c/strong\u003e, assuming:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eSignificance level (\u0026alpha;) = 0.05\u003c/strong\u003e (95% confidence interval).\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePower (1-\u0026beta;) = 80%\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eExpected effect size (d) = 0.5\u003c/strong\u003e, based on previous studies.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe estimated \u003cstrong\u003eminimum sample size was 52 patients\u003c/strong\u003e. To account for potential \u003cstrong\u003elosses (15%)\u003c/strong\u003e, the final sample size was \u003cstrong\u003e60 patients\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eBaseline characteristics\u003c/strong\u003e were compared using \u003cstrong\u003et-tests (continuous variables)\u003c/strong\u003e and \u003cstrong\u003echi-square tests (categorical variables)\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eThe primary outcome (CI-AKI incidence)\u003c/strong\u003e was analyzed using \u003cstrong\u003elogistic regression\u003c/strong\u003e with \u003cstrong\u003eodds ratios (OR) and 95% confidence intervals (CI)\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eRepeated measures ANOVA\u003c/strong\u003e was used to evaluate biomarker variations over time.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ep-values \u0026lt;0.05 were considered statistically significant\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003eAnalyses were performed using \u003cstrong\u003eSPSS 26.0 (IBM Corp.)\u003c/strong\u003e.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary Outcome and Statistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary Outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was the \u003cstrong\u003eincidence of contrast-induced acute kidney injury (CI-AKI)\u003c/strong\u003e, evaluated using two distinct criteria based on \u003cstrong\u003eserum creatinine (sCr) and serum cystatin C (sCys C) levels\u003c/strong\u003e.\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eSerum Creatinine-Based CI-AKI Definition\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cul type=\"circle\"\u003e\n \u003cli\u003e\u003cstrong\u003eAbsolute increase\u003c/strong\u003e in sCr \u003cstrong\u003e\u0026ge;0.5 mg/dL\u003c/strong\u003e\u003cstrong\u003eand/or\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eRelative increase\u003c/strong\u003e of \u003cstrong\u003e\u0026ge;25% from baseline\u003c/strong\u003e, measured \u003cstrong\u003e72 hours post-procedure\u003c/strong\u003e.\u003c/li\u003e\n \u003c/ul\u003e\n\u003c/ol\u003e\n\u003col start=\"2\"\u003e\n \u003cli\u003e\u003cstrong\u003eSerum Cystatin C-Based CI-AKI Definition\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"2\" type=\"1\"\u003e\n \u003cul type=\"circle\"\u003e\n \u003cli\u003e\u003cstrong\u003eIncrease of \u0026ge;10% in sCys C\u003c/strong\u003e\u003cstrong\u003e24 hours after contrast exposure\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003eThis threshold has been well established in previous studies as an \u003cstrong\u003eindependent risk factor\u003c/strong\u003e for CI-AKI.\u003c/li\u003e\n \u003c/ul\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll collected data were recorded in a \u003cstrong\u003eMicrosoft Excel\u0026reg; spreadsheet\u003c/strong\u003e and analyzed using \u003cstrong\u003eIBM SPSS Statistics v26.0 (IBM Corp., Armonk, USA)\u003c/strong\u003e.\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eDescriptive statistics\u003c/strong\u003e:\u003cul type=\"circle\"\u003e\n \u003cli\u003e\u003cstrong\u003eContinuous variables\u003c/strong\u003e: Presented as \u003cstrong\u003emeans and standard deviations\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCategorical variables\u003c/strong\u003e: Presented as \u003cstrong\u003eabsolute and relative frequencies\u003c/strong\u003e (percentages).\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eComparisons between groups\u003c/strong\u003e:\u003cul type=\"circle\"\u003e\n \u003cli\u003e\u003cstrong\u003eChi-square test\u003c/strong\u003e for categorical variables.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003et-tests\u003c/strong\u003e or \u003cstrong\u003eMann-Whitney U tests\u003c/strong\u003e for continuous variables, depending on normality distribution.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eInferential statistics\u003c/strong\u003e:\u003cul type=\"circle\"\u003e\n \u003cli\u003e\u003cstrong\u003eLogistic regression analysis\u003c/strong\u003e was performed to assess the association between the intervention and CI-AKI incidence.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eRepeated-measures ANOVA\u003c/strong\u003e was used to evaluate biomarker variations over time.\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSignificance threshold\u003c/strong\u003e: A \u003cstrong\u003ep-value \u0026lt;0.05\u003c/strong\u003e was considered \u003cstrong\u003estatistically significant\u003c/strong\u003e.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBaseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study enrolled a total of \u003cstrong\u003e76 patients\u003c/strong\u003e, stratified into \u003cstrong\u003ethree renal function groups\u003c/strong\u003e: \u003cstrong\u003eControl (normal renal function), Group 2 (moderate CKD or intermediate), and Group 1 (end-stage renal disease or terminal)\u003c/strong\u003e. Patients were further subdivided based on \u003cstrong\u003eintervention (high-dose atorvastatin + N-acetylcysteine) or standard hydration alone\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eBaseline demographic and clinical characteristics, including \u003cstrong\u003eage, sex, ethnicity, comorbidities (hypertension, diabetes, dyslipidemia), and lifestyle factors\u003c/strong\u003e, were \u003cstrong\u003ehomogeneously distributed across groups\u003c/strong\u003e (Table 1). Pearson\u0026rsquo;s chi-square test indicated \u003cstrong\u003eno statistically significant differences\u003c/strong\u003e between groups, ensuring that subsequent analyses were not confounded by baseline imbalances.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIncidence of CI-AKI Based on Serum Creatinine and Cystatin C\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSerum Creatinine-Based Diagnosis\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eLogistic regression analysis \u003cstrong\u003edid not show a significant effect of the intervention\u003c/strong\u003e on CI-AKI incidence in patients with \u003cstrong\u003enormal renal function (Control Group)\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eNo cases of CI-AKI were detected in Groups 1 (end-stage CKD) and 2 (moderate CKD) using serum creatinine (sCr) criteria\u003c/strong\u003e, preventing statistical assessment of the intervention\u0026rsquo;s impact in these patients (Table 2).\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eSerum Cystatin C-Based Diagnosis\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eWhen CI-AKI was assessed using \u003cstrong\u003eserum cystatin C (sCys C) criteria\u003c/strong\u003e, the intervention \u003cstrong\u003edemonstrated a protective effect in the Control Group\u003c/strong\u003e, but \u003cstrong\u003enot in Groups 1 and 2\u003c/strong\u003e (Table 3).\u003c/li\u003e\n \u003cli\u003eAdditionally, \u003cstrong\u003emore CI-AKI cases were diagnosed using sCys C than sCr\u003c/strong\u003e, suggesting \u003cstrong\u003egreater sensitivity of this biomarker\u003c/strong\u003e.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eImpact of Prior Statin Use on CI-AKI Risk\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eIn patients \u003cstrong\u003ewithout prior statin use\u003c/strong\u003e, the \u003cstrong\u003eodds ratio (OR) \u0026lt;1 suggested a possible reduction in CI-AKI risk with the intervention\u003c/strong\u003e. However, \u003cstrong\u003ea wide confidence interval and a non-significant p-value indicated a lack of statistical significance\u003c/strong\u003e (Table 4).\u003c/li\u003e\n \u003cli\u003eAmong patients \u003cstrong\u003ewith prior statin use\u003c/strong\u003e, \u003cstrong\u003eno CI-AKI cases were detected using sCr\u003c/strong\u003e, preventing statistical evaluation of the intervention\u0026rsquo;s effect.\u003c/li\u003e\n \u003cli\u003eWhen using \u003cstrong\u003esCys C\u003c/strong\u003e, a \u003cstrong\u003enon-significant trend toward renal protection\u003c/strong\u003e was observed in patients \u003cstrong\u003ewith and without prior statin use\u003c/strong\u003e (Table 5).\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation Between Contrast Volume and CI-AKI\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eScatter plot analyses revealed:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eNo significant correlation\u003c/strong\u003e between \u003cstrong\u003econtrast volume and sCr variation\u003c/strong\u003e in patients \u003cstrong\u003ewithout intervention\u003c/strong\u003e, including those in Group 1 (end-stage CKD), despite a \u003cstrong\u003estrong positive trend\u003c/strong\u003e (p = 0.09) (Figure 1).\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003esCys C levels remained stable or declined\u003c/strong\u003e in Groups \u003cstrong\u003eControl and 2\u003c/strong\u003e, suggesting that the \u003cstrong\u003eintervention did not impair renal function and may have provided a stabilizing effect\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003eIn Group \u003cstrong\u003e1 (end-stage CKD), sCys C increased with contrast volume despite intervention\u003c/strong\u003e, indicating a \u003cstrong\u003epartial failure of nephroprotection in this subgroup\u003c/strong\u003e (Figure 2).\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of Intervention on Biomarker Variability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFactorial ANOVA Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003esCr variation differed significantly between groups\u003c/strong\u003e (\u003cstrong\u003ep = 0.01\u003c/strong\u003e), indicating \u003cstrong\u003erenal function-dependent biomarker changes\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eThe intervention had no significant overall effect on sCr variation\u003c/strong\u003e (\u003cstrong\u003ep = 0.90\u003c/strong\u003e), as reflected by similar trends across intervention and non-intervention groups.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eNo significant interaction\u003c/strong\u003e between \u003cstrong\u003egroup and intervention\u003c/strong\u003e was found (\u003cstrong\u003ep = 0.86\u003c/strong\u003e), suggesting that the intervention\u0026apos;s impact did not differ across renal function categories.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003esCys C variation was highest in end-stage CKD patients\u003c/strong\u003e but \u003cstrong\u003eshowed high inter-individual variability\u003c/strong\u003e, limiting statistical significance.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eIndividual Statistical Tests for Biomarker Comparisons\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudent\u0026rsquo;s t-test and Mann-Whitney U test\u003c/strong\u003e were used to compare intervention effects on \u003cstrong\u003eserum creatinine (\u0026Delta;Cr) and serum cystatin C (\u0026Delta;C)\u003c/strong\u003e.\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eControl Group\u003c/strong\u003e:\u003cul type=\"circle\"\u003e\n \u003cli\u003e\u003cstrong\u003eIntervention significantly reduced sCr\u003c/strong\u003e (\u003cstrong\u003ep = 0.027, t-test; p = 0.045, Mann-Whitney\u003c/strong\u003e).\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003esCys C reduction was not statistically significant\u003c/strong\u003e (\u003cstrong\u003ep = 0.127, t-test; p = 0.062, Mann-Whitney\u003c/strong\u003e).\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eEnd-Stage CKD (Group 1)\u003c/strong\u003e:\u003cul type=\"circle\"\u003e\n \u003cli\u003e\u003cstrong\u003esCys C showed a significant protective effect\u003c/strong\u003e (\u003cstrong\u003ep = 0.020, t-test; p = 0.016, Mann-Whitney\u003c/strong\u003e).\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003esCr showed no significant trend\u003c/strong\u003e (\u003cstrong\u003ep = 0.118, t-test; p = 0.111, Mann-Whitney\u003c/strong\u003e).\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThus, \u003cstrong\u003esCys C detected a significant nephroprotective effect in end-stage CKD patients, whereas sCr did not\u003c/strong\u003e, whereas in \u003cstrong\u003epatients with normal renal function, sCr was more responsive to the intervention than sCys C\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelation Between Biomarkers: Creatinine vs. Cystatin C\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eScatter plot analysis of \u003cstrong\u003esCr and sCys C correlation\u003c/strong\u003e revealed:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eNo statistically significant correlation between biomarkers in non-intervention groups\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eIn end-stage CKD (Group 1), sCys C and sCr exhibited a strong negative correlation\u003c/strong\u003e, suggesting that \u003cstrong\u003esCr may not accurately reflect early renal dysfunction\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eWith intervention, this correlation was reversed (-0.81 to 0.05),\u003c/strong\u003e implying that the intervention \u003cstrong\u003ealtered the relationship between biomarkers\u003c/strong\u003e.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eSummary of biomarker trends:\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eWithout intervention\u003c/strong\u003e: No clear correlation in Control and Group 2; \u003cstrong\u003estrong negative correlation in Group 1\u003c/strong\u003e, indicating that \u003cstrong\u003esCr may underdiagnose renal dysfunction\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eWith intervention\u003c/strong\u003e: Biomarker correlation \u003cstrong\u003ebecame weak or neutral\u003c/strong\u003e, suggesting that \u003cstrong\u003ethe intervention may have equalized their diagnostic performance\u003c/strong\u003e.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic Agreement Between Biomarkers (Kappa Test)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA \u003cstrong\u003eKappa concordance test\u003c/strong\u003e was performed to evaluate agreement between \u003cstrong\u003esCr-based and sCys C-based CI-AKI diagnoses\u003c/strong\u003e (Table 6).\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eLow Kappa coefficient (K = 0.07, non-significant p-value)\u003c/strong\u003e indicated \u003cstrong\u003epoor agreement between the two biomarkers\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eNo patient was simultaneously classified as \u0026quot;CI-AKI positive\u0026quot; by both biomarkers\u003c/strong\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSeven patients were diagnosed with CI-AKI by sCys C but not by sCr\u003c/strong\u003e, suggesting \u003cstrong\u003epotential underdiagnosis by sCr\u003c/strong\u003e.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThus, \u003cstrong\u003esCys C may detect renal dysfunction earlier than sCr\u003c/strong\u003e, reinforcing its potential as a \u003cstrong\u003emore sensitive biomarker for CI-AKI\u003c/strong\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e \u003cb\u003eMain Findings\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThis study demonstrated that the \u003cb\u003eincidence of CI-AKI was higher when using serum cystatin C (sCys C) criteria compared to serum creatinine (sCr)\u003c/b\u003e, suggesting that \u003cb\u003esCys C may be a more sensitive biomarker\u003c/b\u003e for detecting contrast-induced renal dysfunction. sCys C is recognized as a \u003cb\u003efunctional biomarker of glomerular filtration rate (GFR)\u003c/b\u003e with greater sensitivity than sCr, as it is \u003cb\u003enot secreted by renal tubules\u003c/b\u003e and reaches its \u003cb\u003epeak concentration within 24 hours post-contrast exposure\u003c/b\u003e, enabling the detection of subtle GFR changes.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eBriguori et al. demonstrated that a\u0026thinsp;\u003cb\u003e\u0026ge;\u0026thinsp;10% increase in sCys C within 24 hours of contrast exposure\u003c/b\u003e was associated with \u003cb\u003ea concurrent increase of \u0026ge;\u0026thinsp;0.3 mg/dL in sCr\u003c/b\u003e and was an \u003cb\u003eindependent risk factor for mortality and dialysis at one year\u003c/b\u003e.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) Despite sCr being the \u003cb\u003emost widely used biomarker for renal function assessment\u003c/b\u003e, its \u003cb\u003edelayed kinetics (24-72h post-exposure, peaking at 3\u0026ndash;5 days, and normalizing in 10\u0026ndash;14 days)\u003c/b\u003e limits its utility for \u003cb\u003eearly CI-AKI detection\u003c/b\u003e. Additionally, \u003cb\u003esCr remains within the reference range until approximately 50% of renal function is lost\u003c/b\u003e, reducing its sensitivity(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003eComparison with Previous Studies\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA potential explanation for the \u003cb\u003elow detection of CI-AKI using sCr\u003c/b\u003e in this study is that the \u003cb\u003ehistorical definition of CI-AKI (Mehran et al., 2004) was used\u003c/b\u003e(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), rather than the \u003cb\u003ecurrent KDIGO definition\u003c/b\u003e, which has been widely accepted by the nephrology community. This discrepancy may have influenced the \u003cb\u003eagreement analysis between biomarkers\u003c/b\u003e, differing from the findings of Fu et al., who reported a \u003cb\u003estrong correlation between sCys C and sCr in CI-AKI diagnosis (95% sensitivity and 79% specificity).\u003c/b\u003e (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Our statistical analysis, employing more robust methodologies, did not demonstrate agreement between \u003cb\u003esCr and sCys C variations\u003c/b\u003e, suggesting that these biomarkers may be reflecting \u003cb\u003edifferent stages of renal dysfunction\u003c/b\u003e rather than diagnosing the same phenomenon.\u003c/p\u003e \u003cp\u003eNevertheless, an important finding of this study is that \u003cb\u003ein the control group, CI-AKI (based on sCys C criteria) was significantly reduced with high-dose atorvastatin\u0026thinsp;+\u0026thinsp;N-acetylcysteine (NAC) intervention\u003c/b\u003e, supporting a \u003cb\u003epotential nephroprotective effect\u003c/b\u003e of this strategy.\u003c/p\u003e \u003cp\u003e \u003cb\u003eEffect of Prior Statin Use\u003c/b\u003e \u003c/p\u003e \u003cp\u003eIn dyslipidemic patients \u003cb\u003ewithout prior statin use\u003c/b\u003e, the intervention \u003cb\u003edid not significantly modify CI-AKI risk\u003c/b\u003e when assessed by sCr levels (\u003cb\u003eOR close to 1, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05\u003c/b\u003e). Among patients \u003cb\u003ewith prior statin use\u003c/b\u003e, \u003cb\u003eno CI-AKI cases were detected using sCr\u003c/b\u003e, making statistical assessment infeasible. These findings raise the possibility that \u003cb\u003epatients on chronic statin therapy may have been preconditioned against CI-AKI development\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eHowever, when using \u003cb\u003esCys C as a biomarker\u003c/b\u003e, the intervention did not significantly impact CI-AKI incidence, regardless of prior statin use. While the odds ratio was \u003cb\u003e\u0026lt;\u0026thinsp;1\u003c/b\u003e, suggesting a \u003cb\u003epotential renoprotective trend\u003c/b\u003e, this effect did not reach statistical significance. These results contrast with \u003cb\u003eQuintavalle et al. and meta-analyses\u003c/b\u003e reporting \u003cb\u003ea protective effect of high-dose atorvastatin (80 mg) in patients with impaired renal function undergoing contrast-enhanced procedures.\u003c/b\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Further studies are needed to clarify the role of statins in CI-AKI prevention, particularly regarding biomarker-dependent differences in diagnostic sensitivity.\u003c/p\u003e \u003cp\u003e \u003cb\u003eContrast Volume and Renal Function\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAssessing the influence of contrast volume on renal function, no \u003cb\u003estatistically significant correlation was found between contrast volume and sCr variations\u003c/b\u003e in non-intervention patients across different renal function strata. However, in \u003cb\u003epatients with intervention (particularly Group 1 - end-stage CKD), a strong positive correlation was observed\u003c/b\u003e, suggesting a \u003cb\u003epotential association between contrast volume and sCr variation\u003c/b\u003e. Although this trend did not reach statistical significance (\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.09\u003c/b\u003e), it indicates that \u003cb\u003ehigher contrast exposure may contribute to renal injury in this subgroup\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eWhen assessing \u003cb\u003esCys C variation\u003c/b\u003e, contrast volume \u003cb\u003edid not show a clear or consistent relationship with renal function\u003c/b\u003e, independent of intervention. This supports the idea that \u003cb\u003esCys C may be less influenced by contrast volume than sCr\u003c/b\u003e, reinforcing its potential utility as an \u003cb\u003eearly biomarker for renal dysfunction\u003c/b\u003e. These findings align with \u003cb\u003eMehran et al. and Maioli et al., who identified an increased CI-AKI risk only with contrast volumes exceeding 350 mL or 4 mL/kg.\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eClinical Implications\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThese findings have \u003cb\u003eimportant implications for clinical practice\u003c/b\u003e, especially given the \u003cb\u003eglobal rise in contrast-enhanced procedures\u003c/b\u003e. Despite advancements in CI-AKI understanding, many aspects of its \u003cb\u003epathophysiology, early diagnosis, and prevention remain incompletely elucidated\u003c/b\u003e. Even with \u003cb\u003emethodologically rigorous studies\u003c/b\u003e, \u003cb\u003esignificant discrepancies persist\u003c/b\u003e regarding \u003cb\u003epreventive strategies and biomarker-based early detection of CI-AKI\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStudy Limitations\u003c/b\u003e \u003c/p\u003e \u003cp\u003eSeveral \u003cb\u003elimitations\u003c/b\u003e should be considered:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eSmall sample size\u003c/b\u003e, which may limit statistical power.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eUse of historical CI-AKI criteria (Mehran et al., 2004)\u003c/b\u003e instead of the \u003cb\u003emore widely accepted KDIGO definition\u003c/b\u003e.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePotential confounding effects of NAC combined with atorvastatin\u003c/b\u003e. While NAC use in CI-AKI prevention remains controversial, a \u003cb\u003elarge-scale study\u003c/b\u003e demonstrated its \u003cb\u003elack of efficacy\u003c/b\u003e in this context.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eFuture Directions\u003c/b\u003e \u003c/p\u003e \u003cp\u003eFuture research should focus on:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eImproving CI-AKI pathophysiological understanding\u003c/b\u003e.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eDeveloping more sensitive and specific early diagnostic methods\u003c/b\u003e.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eIdentifying pharmacological strategies with proven efficacy\u003c/b\u003e in preventing CI-AKI, particularly in high-risk CKD patients.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eGiven its \u003cb\u003eclinical relevance\u003c/b\u003e, CI-AKI remains a \u003cb\u003emajor challenge\u003c/b\u003e for nephrologists and interventionalists, necessitating \u003cb\u003eongoing research efforts to optimize its diagnosis, prevention, and management\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this \u003cb\u003erandomized clinical trial\u003c/b\u003e, serum \u003cb\u003ecreatinine (sCr) and cystatin C (sCys C) did not demonstrate consistent correlation\u003c/b\u003e in the diagnosis of \u003cb\u003econtrast-induced acute kidney injury (CI-AKI)\u003c/b\u003e. This finding suggests that these biomarkers may \u003cb\u003ereflect different aspects of renal function\u003c/b\u003e or that \u003cb\u003eone may lack sufficient sensitivity\u003c/b\u003e for detecting this specific type of renal injury.\u003c/p\u003e \u003cp\u003eThe administration of \u003cb\u003ehigh-dose statins combined with N-acetylcysteine (NAC) significantly reduced CI-AKI incidence in patients with preserved renal function\u003c/b\u003e, when assessed using \u003cb\u003esCys C criteria\u003c/b\u003e. However, this \u003cb\u003enephroprotective effect was not observed\u003c/b\u003e in patients with \u003cb\u003emoderate to severe chronic kidney disease\u003c/b\u003e, regardless of the biomarker used (\u003cb\u003esCr or sCys C\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eMoreover, in \u003cb\u003epatients with and without prior statin use\u003c/b\u003e, the combination of \u003cb\u003ehigh-dose statins and NAC did not significantly impact CI-AKI incidence\u003c/b\u003e, whether evaluated by \u003cb\u003esCr or sCys C levels\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eAdditionally, the \u003cb\u003econtrast volume used during procedures did not influence CI-AKI incidence\u003c/b\u003e, irrespective of the biomarker employed for detection.\u003c/p\u003e \u003cp\u003e \u003cb\u003eClinical Implications and Future Perspectives\u003c/b\u003e \u003c/p\u003e \u003cp\u003eOptimizing \u003cb\u003eCI-AKI detection and prevention\u003c/b\u003e in contrast-enhanced procedures requires \u003cb\u003ea multifactorial approach\u003c/b\u003e, considering:\u003c/p\u003e\u003cp\u003e- \u003cb\u003eBaseline renal function\u003c/b\u003e;\u003c/p\u003e \u003cp\u003e- \u003cb\u003eSelection of the most appropriate biomarker\u003c/b\u003e;\u003c/p\u003e \u003cp\u003e- \u003cb\u003eRefinement of diagnostic criteria\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eThe introduction of \u003cb\u003enovel renal injury biomarkers\u003c/b\u003e may represent a \u003cb\u003esignificant advancement\u003c/b\u003e, enabling \u003cb\u003eearlier detection\u003c/b\u003e and \u003cb\u003emore effective preventive strategies\u003c/b\u003e for CI-AKI.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDisclosures\u003c/strong\u003e: All authors report no relationships that could be construed as a conflict of interest. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This study was self-funded by the author(s), and no external financial support was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUniversal Trial Number,\u0026nbsp;\u003c/strong\u003eWHO International Clinical Trials Registry Platform: U1111-1277-3145\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the hospital\u0026apos;s Ethics Committee and the Goi\u0026aacute;s State Health Department (Approval Number: 5.307.711)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors report no relationships that could be construed as a conflict of interest. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was entirely funded by the corresponding author with personal resources\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDCMF wrote the main manuscript, design of the work; the acquisition, analysis and interpretation of data\u003c/p\u003e\n\u003cp\u003eRG analysis and interpretation of data.\u003c/p\u003e\n\u003cp\u003eTM \u0026nbsp;acquisition, analysis and interpretation of data\u003c/p\u003e\n\u003cp\u003eRTL acquisition, analysis and interpretation of data\u003c/p\u003e\n\u003cp\u003eRMS acquisition, analysis and interpretation of data\u003c/p\u003e\n\u003cp\u003ePRM acquisition, analysis, interpretation of data and prepared figures\u003c/p\u003e\n\u003cp\u003eAR acquisition, analysis and interpretation of data\u003c/p\u003e\n\u003cp\u003eDVN prepare figure and tables\u003c/p\u003e\n\u003cp\u003eMLA acquisition, analysis and interpretation of data\u003c/p\u003e\n\u003cp\u003eLP acquisition, analysis and interpretation of data\u003c/p\u003e\n\u003cp\u003eMB acquisition, analysis , interpretation of data and revised manuscript\u003c/p\u003e\n\u003cp\u003eMLS acquisition, analysis , interpretation of data and revised manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author would like to thank the entire Vascular Surgery team and the biochemists from the General Hospital of Goi\u0026acirc;nia for their valuable contributions. Special thanks also go to the INGOH Laboratory in Goi\u0026acirc;nia. All of them were essential for the execution of this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAzzalini, L. \u0026amp; Kalra, S. Contrast-Induced Acute Kidney Injury-Definitions, Epidemiology, and Implications. \u003cem\u003eInterv Cardiol. Clin.\u003c/em\u003e \u003cb\u003e9\u003c/b\u003e (3), 299\u0026ndash;309 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNash, K., Hafeez, A. \u0026amp; Hou, S. Hospital-acquired renal insufficiency. \u003cem\u003eAm. J. Kidney Dis. Off J. Natl. Kidney Found.\u003c/em\u003e \u003cb\u003e39\u003c/b\u003e (5), 930\u0026ndash;936 (2002).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorcos, S. K. Prevention of contrast media-induced nephrotoxicity after angiographic procedures. \u003cem\u003eJ. Vasc Interv Radiol. JVIR\u003c/em\u003e. \u003cb\u003e16\u003c/b\u003e (1), 13\u0026ndash;23 (2005).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScharnweber, T., Alhilali, L. \u0026amp; Fakhran, S. Contrast-Induced Acute Kidney Injury: Pathophysiology, Manifestations, Prevention, and Management. \u003cem\u003eMagn. Reson. Imaging Clin. N Am.\u003c/em\u003e \u003cb\u003e25\u003c/b\u003e (4), 743\u0026ndash;753 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang, J. S. et al. The molecular mechanism of contrast-induced nephropathy (CIN) and its link to in vitro studies on iodinated contrast media (CM). \u003cem\u003eBioMedicine\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e (1), 1 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEng, J. et al. Comparative Effect of Contrast Media Type on the Incidence of Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis. \u003cem\u003eAnn. Intern. Med.\u003c/em\u003e \u003cb\u003e164\u003c/b\u003e (6), 417\u0026ndash;424 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarbieri, L. et al. The role of statins in the prevention of contrast induced nephropathy: a meta-analysis of 8 randomized trials. \u003cem\u003eJ. Thromb. Thrombolysis\u003c/em\u003e. \u003cb\u003e38\u003c/b\u003e (4), 493\u0026ndash;502 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD\u0026rsquo;Amore, C., Nuzzo, S. \u0026amp; Briguori, C. Biomarkers of Contrast-Induced Nephropathy:: Which Ones are Clinically Important? \u003cem\u003eInterv Cardiol. Clin.\u003c/em\u003e \u003cb\u003e9\u003c/b\u003e (3), 335\u0026ndash;344 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuwabara, T. et al. Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. \u003cem\u003eKidney Int.\u003c/em\u003e \u003cb\u003e75\u003c/b\u003e (3), 285\u0026ndash;294 (2009).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBriguori, C. et al. Cystatin C and contrast-induced acute kidney injury. \u003cem\u003eCirculation\u003c/em\u003e \u003cb\u003e121\u003c/b\u003e (19), 2117\u0026ndash;2122 (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehran, R. et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. \u003cem\u003eJ. Am. Coll. Cardiol.\u003c/em\u003e \u003cb\u003e44\u003c/b\u003e (7), 1393\u0026ndash;1399 (2004).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFu, N., Liang, M. \u0026amp; Yang, S. High Loading Dose of Atorvastatin for the Prevention of Serum Creatinine and Cystatin C-Based Contrast-Induced Nephropathy Following Percutaneous Coronary Intervention. \u003cem\u003eAngiology\u003c/em\u003e \u003cb\u003e69\u003c/b\u003e (8), 692\u0026ndash;699 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlharazy, S. M. et al. Serum neutrophil gelatinase-associated lipocalin and cystatin C are early biomarkers of contrast-induced nephropathy after coronary angiography in patients with chronic kidney disease. \u003cem\u003eAngiology\u003c/em\u003e \u003cb\u003e65\u003c/b\u003e (5), 436\u0026ndash;442 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQuintavalle, C. et al. Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury. \u003cem\u003eCirculation\u003c/em\u003e \u003cb\u003e126\u003c/b\u003e (25), 3008\u0026ndash;3016 (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheungpasitporn, W. et al. Periprocedural effects of statins on the incidence of contrast-induced acute kidney injury: a systematic review and meta-analysis of randomized controlled trials. \u003cem\u003eRen. Fail.\u003c/em\u003e \u003cb\u003e37\u003c/b\u003e (4), 664\u0026ndash;671 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeisbord, S. D. et al. Prevention of contrast-induced AKI: a review of published trials and the design of the prevention of serious adverse events following angiography (PRESERVE) trial. \u003cem\u003eClin. J. Am. Soc. Nephrol. CJASN\u003c/em\u003e. \u003cb\u003e8\u003c/b\u003e (9), 1618\u0026ndash;1631 (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaioli, M. et al. Preprocedural score for risk of contrast-induced nephropathy in elective coronary angiography and intervention. \u003cem\u003eJ. Cardiovasc. Med. Hagerstown Md.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e (6), 444\u0026ndash;449 (2010).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":" \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eCharacterization of the patient profile according to groups and intervention\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eWhithout Intervenction\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep*\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eWhith Intervention\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep*\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003en (%)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eNormal\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eIntermediate\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eTerminal\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eNormal\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eIntermediate\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003eTerminal\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eAge Group\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e31 a 59 anos\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (19,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,203\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (20,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,074\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e60 ou mais\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e17 (81,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e11 (100,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e16 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e12 (100,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (80,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGender\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 (23,8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,511\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e12 (50,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (20,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,369\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e16 (76,2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 (90,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e12 (50,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (80,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eRace\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWhite\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 (47,6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 (45,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,657\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e15 (62,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 (41,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (40,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,286\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eBlack\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (18,2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (20,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMixed\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 (47,6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (36,4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e7 (58,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (40,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eHypertension\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 (47,6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (27,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,200\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e7 (29,2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,312\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e11 (52,4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (72,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (100,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e17 (70,8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 (83,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 (100,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDiabete\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e12 (57,1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 (90,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,148\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e12 (50,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (60,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,626\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e9 (42,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e12 (50,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (40,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDyslipidemia\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e17 (81,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (72,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,782\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e21 (87,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 (83,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (80,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,886\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (19,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (27,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (20,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSmoker\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e7 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (36,4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,986\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e9 (37,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (40,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,410\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e14 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e7 (63,6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e15 (62,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 (83,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (60,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eProcedure Performed\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAngioplasty\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 (23,8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,433\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 (20,8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (20,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,683\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAortography\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (33,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 (20,8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eArteriography\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e15 (71,4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e9 (81,8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e14 (58,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (80,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003en, absolute frequency; %, relative frequency.\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eAssociation of renal injury (Cr) prevalence among patients with and without intervention according to renal function groups.\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eRenal Function\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eRenal Injury\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eOdds Ratio(OR) IC 95%\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep*\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eNormal\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWithout intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e19 (46,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (50,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,86 (0,66\u0026thinsp;\u0026minus;\u0026thinsp;6,73)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,889\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWith intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e22 (53,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (50,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIntermediate\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWithout intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e11 (47,8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003ena\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003ena\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWith intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e12 (52,2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTerminal\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWithout intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (37,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003ena\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003ena\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWith intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5 (62,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e* \u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eNote\u003c/span\u003e: \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eSimple logistic regression; NA, not applicable; n, absolute frequency; %, relative frequency.\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eAssociation of renal injury (C) prevalence among patients with and without intervention according to renal function groups.\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eRenal Function\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eRenal Injury\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eOdds Ratio(OR) IC 95%\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep*\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eNormal\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWithout intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e17 (41,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (100,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,81 (0,65\u0026thinsp;\u0026minus;\u0026thinsp;0,98)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e0,025\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWith intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e24 (58,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIntermediate\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWithout intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e10 (47,6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (50,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,90 (0,05\u0026thinsp;\u0026minus;\u0026thinsp;1,65)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,942\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWith intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e11 (52,4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (50,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTerminal\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWithout intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3 (42,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1,25 (0,81\u0026thinsp;\u0026minus;\u0026thinsp;1,93)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,408\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWith intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (57,1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (100,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e* \u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eNote\u003c/span\u003e: \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eSimple logistic regression; NA, not applicable; n, absolute frequency; %, relative frequency.\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eAssociation of renal injury incidence (ΔCr) among patients with and without intervention according to prior statin use.\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003ePrior Statin Use\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eRenal Injury\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eOdds Ratio (OR) IC 95%\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep*\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eNo prior statin use\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWithout intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e25 (43,1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (50,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,75 (0,15\u0026thinsp;\u0026minus;\u0026thinsp;5,75)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,788\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWith intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e33 (56,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (50,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ePrior statin use\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWithout intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e8 (57,1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003ena\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003ena\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWith intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6 (42,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e\u003cem\u003eSimple logistic regression; NA, not applicable; n, absolute frequency; %, relative frequency.\u003c/em\u003e\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eAssociation of renal injury incidence (ΔC) among patients with and without intervention according to prior statin use.\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003ePrior Statin Use\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eRenal Injury\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eOdds Ratio (OR) IC 95%\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep*\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eNo prior statin use\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWithout intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e23 (41,1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (66,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,34 (0,06\u0026thinsp;\u0026minus;\u0026thinsp;2,06)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,221\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWith intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e33 (58,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2 (33,3)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ePrior statin use\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWithout intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e7 (53,8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 (100,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,31 (0,05\u0026thinsp;\u0026minus;\u0026thinsp;1,69)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,369\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eWith intervention\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6 (46,2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eNote\u003c/span\u003e: \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eSimple logistic regression; NA, not applicable; n, absolute frequency; %, relative frequency.\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eConcordance analysis between renal injury by C and Cr.\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eCr\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eKappa\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eC\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eTotal\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e65 (90,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 (100,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e69\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e7 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0 (0,0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e7\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,07\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,554\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTotal\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e72\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e76\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eNote\u003c/span\u003e: \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eKappa; n, absolute frequency; % relative frequency.\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cystatin C, Creatinine, Contrast-induced nephropathy, Chronic kidney disease, Preventive strategies","lastPublishedDoi":"10.21203/rs.3.rs-6387719/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6387719/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eContrast-induced acute kidney injury (CI-AKI) remains a clinically relevant complication, with uncertainties regarding its true epidemiology, pathophysiology, optimal diagnostic methods, and preventive strategies. As the global volume of contrast-enhanced imaging procedures continues to rise, there is a critical need to refine early detection and prevention approaches.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective, randomized clinical trial included patients with peripheral artery disease requiring contrast-enhanced diagnostic and/or therapeutic procedures at a public hospital from February 2022 to March 2024. Patients were stratified into three groups based on their estimated glomerular filtration rate (eGFR): \u003cb\u003econtrol group\u003c/b\u003e (eGFR\u0026thinsp;\u0026gt;\u0026thinsp;60 mL/min/1.73m\u0026sup2;), \u003cb\u003eGroup 1\u003c/b\u003e (eGFR\u0026thinsp;\u0026lt;\u0026thinsp;30 mL/min/1.73m\u0026sup2;), and \u003cb\u003eGroup 2\u003c/b\u003e (eGFR 30\u0026ndash;59 mL/min/1.73m\u0026sup2;). Within each group, patients were randomized into either a \u003cb\u003estandard hydration protocol (\u003c/b\u003e1 mL/kg/h for 12 hours before and 12 hours after the procedure\u003cb\u003e)\u003c/b\u003e or an \u003cb\u003eintervention protocol\u003c/b\u003e, which included atorvastatin (80 mg 12 hours before and 40 mg after the procedure) and oral N-acetylcysteine (600 mg every 12 hours, starting 24 hours before and continuing for 24 hours after the procedure), in addition to intravenous isotonic saline hydration. Serum creatinine (sCr) and cystatin C (sCys C) levels were measured at baseline, 24h, and 72h post-procedure.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of \u003cb\u003e76 patients\u003c/b\u003e were included: \u003cb\u003e45 in the control group, 23 in Group 2, and 8 in Group 3\u003c/b\u003e. There were no significant differences in baseline clinical or demographic characteristics between groups. Although numerically more CI-AKI cases were identified using sCys C, it did not demonstrate statistically significant superiority over sCr as a diagnostic biomarker (Kappa\u0026thinsp;=\u0026thinsp;0.07, p\u0026thinsp;=\u0026thinsp;0.554). In the \u003cb\u003econtrol group\u003c/b\u003e, logistic regression analysis showed that the intervention was associated with a lower incidence of CI-AKI when sCys C was used as the diagnostic criterion (OR 0.81; 95% CI, 0.65\u0026ndash;0.98; p\u0026thinsp;=\u0026thinsp;0.025). However, this effect was not statistically significant in patients with impaired renal function. Factorial ANOVA and dispersion analysis did not confirm a significant effect of the intervention across groups or its interaction with renal function status when evaluating variations in both sCys C and sCr (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eWhen using sCys C as a diagnostic criterion, the combination of high-dose atorvastatin and N-acetylcysteine demonstrated a \u003cb\u003eprotective effect against CI-AKI in patients with normal renal function\u003c/b\u003e. However, this benefit was not observed in patients with moderate or severe chronic kidney disease, regardless of the biomarker used (sCr or sCys C). Furthermore, despite identifying more CI-AKI cases, sCys C did not exhibit statistically significant superiority over sCr for early CI-AKI diagnosis.\u003c/p\u003e","manuscriptTitle":"Contrast-Induced Nephropathy: Evaluation of Preventive Strategies Based on Serum Creatinine and Cystatin C in Patients with Moderate to Severe Chronic Kidney Disease – A Randomized Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-08 12:24:53","doi":"10.21203/rs.3.rs-6387719/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e5047cb9-a1e4-4416-bd9d-26d84005dbd2","owner":[],"postedDate":"April 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":46745277,"name":"Health sciences/Biomarkers"},{"id":46745278,"name":"Health sciences/Cardiology"},{"id":46745279,"name":"Health sciences/Medical research"},{"id":46745280,"name":"Health sciences/Nephrology"}],"tags":[],"updatedAt":"2025-07-28T17:21:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-08 12:24:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6387719","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6387719","identity":"rs-6387719","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}