Statin use and in-hospital outcomes among chronic kidney disease patients: a retrospective cohort study

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Statins were recommended in CKD for cardiovascular benefits, while their effect on AKI remains inconsistent. Methods All adult hospital admissions between January 1, 2018, and December 31, 2020 were retrospectively screened, and CKD patients were included. Exposure was defined as any statin prescription within 48 hours of admission. Patients were followed up until death or discharge or a maximum period of up to 30 days. The primary outcome was in-hospital AKI, and the secondary outcome was in-hospital mortality. Results Among 5,376 patients enrolled, the median age was 72 years, 3,184 (59.2%) were male, and 2,129 (39.6%) were statin users. In-hospital AKI occurred in 149(7.0%) of statin users and 213(6.6%) of non-users. Statin use was associated with a significantly decreased risk of in-hospital AKI (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI] 0.57–0.96), and in-hospital mortality (aHR 0.44; 95% CI 0.23–0.82). A significantly decreased risk of in-hospital AKI was observed in both atorvastatin users and rosuvastatin users. These findings remained consistent in subgroup analyses stratified by age, gender, baseline eGFR, and cardiovascular disease (All P for interaction > 0.05). Conclusions Statins may not only improve survival but also protect against AKI in CKD patients. acute kidney injury statin chronic kidney disease mortality Figures Figure 1 Figure 2 Background Statins are broadly prescribed for lipid management, and their cardiovascular benefits in the general population are well demonstrated by numerous high-quality trials 1–4 . Stains were also found to reduce mortality in chronic kidney disease (CKD) and thus promoted by guidelines 5 . However, in clinical practice, non-adherence to the recommendation of statin use in CKD was common 6 because it’s difficult for clinicians to balance drug safety and efficacy in this special population with decreased kidney clearance, multiple morbidities, and comedication. Acute kidney injury (AKI), the sudden loss of kidney function, is rarely reported as an adverse effect of statins in clinical trials 7 . However, real-world studies showed statin use contributed to the risk of AKI 8–10 . In a cohort of 43,438 patients who were followed for up to 6.5 years, statin users were 30% more likely to develop AKI compared with non-users 11 . This discrepancy may be attributed to selection bias as patients at high risk of AKI (e.g. patients with advanced CKD or acute illness) may be preferably not included in clinical trials. To date, limited data has focused on the influence of statins on AKI in CKD patients, and both protective as well as detrimental effects were reported 10,12–17 . Therefore, in this retrospective study, we aimed to investigate the impact of statin use on in-hospital outcomes in CKD patients, with in-hospital AKI being the primary outcome and in-hospital mortality as the secondary outcome. Methods Study population This observational retrospective cohort study was conducted at the Peking University First Hospital, China. All adult hospital admissions from January 1, 2018, to December 31, 2020 were screened, and those with CKD on admission were included. CKD was defined as a baseline estimated glomerular filtration rate (eGFR) < 60 ml/min.1.73m 2 , calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Eq. 1 8 using the first serum creatinine (SCr) measurement within 48 hours of admission. Patients were excluded if they ( 1 ) had a hospital stay of less than 24 hours; ( 2 ) had SCr detected less than two times during hospitalization; ( 3 ) had a baseline eGFR < 15 mL/min/1.73 m 2 or on dialysis; ( 4 ) with admitting diagnosis of AKI; ( 5 ) developed AKI within 48 hours of admission. Only the first admission that met the criteria was included in the event of readmissions. Data collection Patient data were systematically collected through medical chart abstraction using the institution’s clinical data warehouse, which includes all inpatient information. The baseline was defined as 48 hours of admission. We included demographic data, chronic comorbidities, admission department, surgery information, concomitant medications, and laboratory tests. Chronic comorbidities were identified according to admission diagnosis using the International Classification of Diseases-10th revision (ICD-10) codes. Concomitant medications were determined according to prescriptions. Patients were followed up until death or discharge or 30 days after admission, whichever came first. All SCr values were recorded to identify AKI. Statin exposure Statin use was defined as at least one prescription of statins within 48 hours of admission. Stain type and dose were classified by the first prescription. Statin intensity was classified into low, moderate, and high according to the American College of Cardiology/American Heart Association Guideline on the Management of Blood Cholesterol 19 . Clinical outcomes The primary outcome is AKI, defined as an increase in SCr by 50% or greater within 7 days or 26.5 mmol/L within 48 hours during follow-up, according to the 2012 KDIGO AKI criteria 20 . The secondary outcome is in-hospital mortality, defined as all causes of death during follow-up. We initially planned to explore the association between statin use and myopathic injury, defined as a raised creatine kinase concentration of four or more times the upper limit of normal. However, given that myopathic injury occurred in only a minority of the population (0.7%, 36/5376), there was insufficient statistical power to explore this hypothesis. Statistical analysis Categorical variables were expressed as frequencies, and Chi-square or Fisher exact test was used to compare groups. Whereas continuous variables were expressed as medians (interquartile range), non-parametric tests were used for group comparisons. We used COX proportional hazard models to estimate the hazard ratio of outcomes, adjusting for 19 prespecified covariates. Covariates were chosen based on clinical experience, related literature 13,21–24 , and accessibility, including age, gender, body mass index, ICU admission(defined as hospitalized in ICU or transferred to ICU within 48 hours of admission), chronic comorbidities (diabetes, cardiovascular disease, cerebrovascular disease, severe liver disease, and malignancy), concomitant medications (contrast, proton pump inhibitors, renin-angiotensin-aldosterone system inhibitors, diuretics, non-steroidal anti-inflammatory drugs), and baseline laboratory tests (eGFR, hemoglobin, serum albumin, creatine kinase, and D-dimer). Multiple imputations were used to address missing values. We also conducted prespecified subgroup analyses, including age, gender, baseline eGFR, and cardiovascular disease, and considered a P value less than 0.05 as a significant interaction. We initially planned to evaluate the relationship between statin intensity and outcomes. However, given that most patients (1958/2129, 92.0%) received moderate-intensity statin, there was insufficient statistical power to explore this hypothesis. Statin types were classified into atorvastatin, rosuvastatin, and other statins, as the first two are most commonly used in the study population. We performed two sensitivity analyses to examine whether potential bias could have been introduced by statin initiation/discontinuation. First, we excluded those who discontinued statins during follow-up and defined statin users as those who took statins within 48 hours of admission and continued using them during follow-up. Second, we further excluded those who initiated statins after the baseline phase and defined non-users as those who did not use statins throughout the follow-up. All analyses were performed using R software (R, version 4.2.1). Results Clinical characteristics A total of 5,376 CKD patients were included in this study (Fig. 1 ). The median age was 72 years, and 59.2% were male. The median baseline eGFR was 47.9 ml/min/1.73m 2 . Of these patients, 2,129 (39.6%) were prescribed statin within 48 hours of admission (statin users). Compared with non-users, statin users were older, more likely to have an ICU admission, and had a higher comorbidity burden except for severe liver disease and malignancy. Likewise, more frequent use of concomitant medications was also found in statin users. There was no significant difference in baseline eGFR between statin users and non-users (Table 1 ). Table 1 Baseline characteristics of hospitalized CKD patients, categorized into statin users and non-users. All subjects (N = 5376) Statin user (N = 2129) Statin non-user (N = 3247) P value Age (y) 72.0(61.0,81.0) 75.0(65.0,82.0) 70.0(59.0,79.0) < 0.001 Male, n (%) 3184(59.2) 1293(60.7) 1891(58.2) 0.069 Body mass index(kg/m 2 ) 25.0(22.0,27.0) 25.0(23.0,28.0) 24.0(22.0,27.0) < 0.001 ICU admission * 462(8.6) 306(14.4) 156(4.8) < 0.001 Chronic comorbidity, n (%) Dyslipidemia 1879(35.0) 1493(70.1) 386(11.9) < 0.001 Hypertension 3821(71.1) 1810(85.0) 2011(61.9) < 0.001 Diabetes 1965(36.6) 1090(51.2) 875(26.9) < 0.001 Cardiovascular disease 2369(44.1) 1575(74.0) 794(24.5) < 0.001 Cerebrovascular disease 1064(19.8) 673(31.6) 391(12.0) < 0.001 Peripheral vascular disease 1014(18.9) 747(35.1) 267(8.2) < 0.001 Severe liver disease 89(1.8) 9(0.4) 80(2.5) < 0.001 Malignancy 1147(21.3) 221(10.4) 926(28.5) < 0.001 Concomitant medication, n (%) Contrast 284(5.3) 119(5.6) 165(5.1) 0.416 Proton pump inhibitors 1497(27.8) 852(40.0) 645(19.9) < 0.001 Non-statin lipid-lowering agents 199(3.7) 156(7.3) 43(1.3) < 0.001 RAAS inhibitor 1753(32.6) 1118(52.5) 635(19.6) < 0.001 β-blockers 1380(25.7) 962(45.2) 418(12.9) < 0.001 Diuretics 1457(27.1) 901(42.3) 556(17.1) < 0.001 NSAIDs 1603(29.8) 1247(58.6) 356(11.0) < 0.001 Anticoagulants 1974(36.7) 1313(61.7) 661(20.4) < 0.001 Baseline laboratory tests eGFR(ml/min.1.73m 2 ) 47.9(37.3,54.8) 47.6(37.7,54.5) 48.0(37.0,55.1) 0.679 Hemoglobin(g/L) 124.0(109.0,136.0) 125.0(111.0,136.0) 124.0(107.0,137.0) 0.012 Serum albumin(g/L) 39.3(35.2,42.7) 38.7(35.2,41.8) 39.8(35.2,43.3) < 0.001 LDL-C(mmol/L) 2.4(1.8,3.1) 2.1(1.6,2.8) 2.6(2.1,3.2) < 0.001 ALT(U/L) 15.0(11.0,22.0) 16.0(11.0,23.0) 14.0(10.0,22.0) < 0.001 CK(U/L) 79.0(51.0,123.0) 85.0(57.0,135.0) 73.0(47.0,116.0) < 0.001 D-dimer(mg/L) 0.2(0.1,0.4) 0.2(0.1,0.4) 0.2(0.1,0.5) 0.019 * Hospitalized in ICU or transferred to ICU within 48 hours of admission. Missing value: Body mass index (140), hemoglobin ( 41 ), AST (72), ALT (71), serum albumin ( 40 ), LDL-C (743), CK (1063), D-dimer (320). ICU, intensive care unit;RAAS inhibitors, renin-angiotensin-aldosterone system inhibitors; NSAIDs, nonsteroidal anti-inflammatory drugs; eGFR, estimated glomerular filtration rate; LDL-C, low-density lipoprotein cholesterol; ALT, alanine transaminase; AST, Aspartate transaminase; CK, creatine kinase. Supplemental Table 1 Sensitivity analysis of the association between statin use and primary and secondary outcome Association between statin use and in-hospital AKI During 9 ( 6 , 14 ) days of follow-up, 362 in-hospital AKI were recorded. The incidence of in-hospital AKI was 7.0% (149/2129) in statin users and 6.6% (213/3247) in non-users. No significant association was found between statin use and AKI in the unadjusted model (hazard ratio [HR], 1.08; 95% CI, 0.87–1.33). After adjusting for selected variables, statin use was associated with a decreased risk of AKI (aHR, 0.74; 95% CI, 0.57–0.96) (Table 2 ). The protective effect against in-hospital AKI was observed in atorvastatin (aHR 0.74; 95% CI 0.55–0.99) and rosuvastatin users (aHR 0.61; 95% CI 0.38–0.98) in the adjusted model (Table 3 ). Table 2 Association between statin use with primary and secondary outcome in hospitalized CKD patients. Outcome No. of Patients with Event (%) Hazard Ratio (95% Confidence Interval) Statin user Statin non-user Unadjusted Adjusted a Acute kidney injury 149(7.0) 213(6.6) 1.08(0.87,1.33) 0.74(0.57,0.96) In hospital mortality 17(0.8) 56(1.7) 0.47(0.27,0.81) 0.44(0.23,0.82) a Adjusted for: age, gender, body mass index, chronic comorbidity (diabetes, cardiovascular disease, cerebrovascular disease, severe liver disease, malignancy), ICU admission, medication (contrast, proton pump inhibitor, renin-angiotensin-aldosterone system inhibitors, diuretic, non-steroidal anti-inflammatory drugs), laboratory tests (hemoglobin, serum albumin, eGFR, creatine kinase, D-dimer) Table 3 Association of different types of statin with primary and secondary outcome. Acute kidney injury In hospital mortality Events (%) Unadjusted HR (95%CI) Adjusted HR (95%CI) a Events (%) Unadjusted HR (95%CI) Adjusted HR (95%CI) a Non-users (N = 3247) 213(6.6) Reference Reference 56(1.7) Reference Reference Atorvastatin users (N = 1350) 103(7.6) 1.18(0.93,1.49) 0.74(0.55,0.99) 12(0.9) 0.53(0.28,0.98) 0.49(0.24,1.00) Rosuvastatin users (N = 453) 24(5.3) 0.80(0.52,1.22) 0.61(0.38,0.98) 4(0.9) 0.51(0.18,1.40) 0.49(0.17,1.44) Other statin users (N = 326) 22(6.7) 1.06(0.68,1.64) 0.99(0.61,1.60) 1(0.3) 0.19(0.03,1.35) 0.21(0.03,1.59) a Adjusted for: age, gender, body mass index, chronic comorbidity (diabetes, cardiovascular disease, cerebrovascular disease, severe liver disease, malignancy), acute illness (ICU admission within 48 hours of admission), medication (contrast, proton pump inhibitor, renin-angiotensin-aldosterone system inhibitors, diuretic, non-steroidal anti-inflammatory drugs), laboratory tests (hemoglobin, serum albumin, eGFR, creatine kinase, D-dimer) As shown in Fig. 2 , the associations of statin use with AKI were broadly similar among subgroups classified by age, gender, baseline eGFR, and cardiovascular disease (all P for heterogeneity > 0.05). In sensitivity analysis, we evaluated the association between statin use and AKI in the population that excluded patients who discontinued statin during hospitalization (aHR, 0.69, 95%CI 0.52–0.91) and in the population that further excluded patients who initiated statin after the baseline phase (aHR 0.71, 95%CI 0.53–0.96); both confirmed the robustness of our conclusions ( Supplemental Table 1 ). Association between statin use and in-hospital mortality During 9 ( 6 , 15 ) days of follow-up, a total of 73 patients died. Statin users had a significantly lower in-hospital mortality rate than non-users (0.8% vs 1.7%, P < 0.001). As shown in Table 2 , a significant association between statin use and in-hospital mortality was observed in the unadjusted model (hazard ratio [HR], 0.47; 95% CI, 0.27–0.81). After adjusting for potential confounders, the association was enhanced and remained statistically significant (aHR 0.44, 95% CI 0.23–0.82). The in-hospital mortality rate was 0.9% (12/1350) in atorvastatin users, 0.9% (4/453) in rosuvastatin users, and 0.3% (1/326) in other statin users, although the association remained significant only in atorvastatin users (aHR 0.49, 95%CI 0.24-1.00) (Table 3 ). Results from the subgroup analysis were consistent with the main results as the associations of statin use with in-hospital mortality were broadly similar among subgroups classified by age, gender, baseline eGFR, and cardiovascular disease (all P for heterogeneity > 0.05) ( Supplemental Fig. 1 ). In sensitivity analysis, statin use remained to be associated with decreased in-hospital mortality when we redefined statin users (aHR 0.28, 95%CI 0.13–0.61) and further redefined non-statin users (aHR 0.24, 95%CI 0.11–0.52) ( Supplemental Table 1 ). Discussion In this retrospective study of 5,376 hospitalized CKD patients, we found statin use was associated with a 26% reduction in in-hospital AKI and a 56% reduction in in-hospital mortality. These findings remained consistent in subgroup analyses stratified by age, gender, baseline eGFR, and cardiovascular disease. The protective effects of statins on cardiovascular events were fully proven in the general population 25–28 and non-dialysis CKD patients 17,29–31 . Therefore, the 2013 Kidney Disease Improving Global Outcomes (KDIGO) guidelines promote their use for lipid management in CKD 20 . Despite the evidence-based recommendation, statin under-prescribing was reported in CKD as drug safety is a major issue in this special population 6,32–34 . AKI is a common complication in CKD patients, especially when they are hospitalized for acute illness. Unlike cardiovascular benefits, the impact of statins on AKI remains uncertain 10,12–17 . In AKI animal models 35,36 , pretreatment with statins could improve the course of kidney injury via decreasing oxidation stress, ameliorating endothelial dysfunction, and reversing increased vascular permeability. Statin use was also reported to be associated with reduced incidence of AKI in different clinical scenarios (e.g., exposure to iodinated contrast agents 37 , surgery 22 , infection 38 , and critical condition 39 ). Controversially, in a large clinical trial including 1,922 patients undergoing cardiac surgery, treatment with rosuvastatin was associated with an increased risk of postoperative AKI 40 . The excess risk of AKI among statin users was also observed in an earlier population-based cohort study of more than 2 million patients in England and Wales 9 . Different statin intensities might contribute to the previous inconsistent findings. Compared with moderate-intensity statins, high-intensity statins are more efficient for improving cardiovascular disease and thus are favored for high-risk patients 41–44 . Yet a considerable body of evidence 8–10,23,45–47 proved that statins also contribute to the risk of AKI with an intensity-response effect. In our study, most patients were prescribed a moderate-intensity statin, which might relate to patient characteristics (elderly, decreased kidney function, comorbidities, and polypharmacy). That could explain why statin use showed a protective effect against AKI in hospitalized CKD patients. Our findings supported that moderate-intensity statins may be beneficial for kidney function in the presence of CKD; whether high-intensity statins have similar kidney-protective effects in CKD patients remains uncertain. The survival benefit of statins in the general population and patients with existing cardiovascular disease was fully proved by many large randomized controlled trials 48–51 . This benefit was also evident in CKD patients. A post hoc analysis of JUPITER trial 30 showed that statin users experience a significant reduction in all-cause mortality (HR 0.56, 95% CI 0.37–0.85) in patients with eGFR less than 60 ml/min/1.73m 2 . Another trial 52 included patients with eGFR 30-<60 ml/min/1.73m 2 also found a significant association between statin use and reduced mortality (HR 0.49, 95% CI 0.27–0.89). Although SHARP study 31 did not find a similar reduction in mortality in CKD patients, it is worth mentioning that 1/3 of the study population was on dialysis, which may attenuate the impact of statins 53–55 . Our findings also add to the existing evidence of the survival benefit of statins in non-dialysis CKD patients. This study has several limitations. First, due to the lack of outpatient data, the duration of preadmission statin use could not be ascertained. Second, due to the observational nature of the study, causality cannot be determined on the current design; we performed the multivariable adjustment and sensitivity analysis to lower the chances of bias, and the findings remained consistent. Third, using baseline eGFR to define CKD might capture patients with community-acquired AKI who fluctuate across the eGFR cutoff; we excluded patients with admitting diagnosis of AKI or those who developed AKI within 48 hours of admission to minimize this incorrect capture. Finally, the impact of statin intensity could not be evaluated due to insufficient statistical power. Conclusions Statin use may not only improve survival but also protect against AKI in CKD patients. Further study is required to determine the safety and efficacy of statin intensities in this population. Abbreviations AKI acute kidney injury ALT alanine transaminase AST aspartate transaminase BMI body mass index CK creatine kinase CKD chronic kidney disease eGFR estimated glomerular filtration rate ICU intensive care unit LDL-C low-density lipoprotein cholesterol NSAIDs nonsteroidal anti-inflammatory drug RAAS renin-angiotensin-aldosterone system SCr serum creatinine Declarations Acknowledgments None. Authors’ contributions Conception, X.-Z.Z. and L.Y.; methodology and formal analysis, X.-Z.Z. and L.-E.T; investigation, X.-Z.Z.; data extraction and curation, L.-E.T., Q.-Q.Z., L.-Y.X., D.-M.X., Y.-L.Z., Y.-D.Z.; writing— original draft preparation, X.-Z.Z. and L.-E.T.; writing—review and editing, J.-C.L., and L.Y. All authors have read and agreed to the published version of the manuscript. Funding Beijing Nova Program (2021051); the Fundamental Research Funds for the Central Universities, Peking University Clinical Scientist Training Program (BMU2023PYJH023); the Capital's Funds for Health Improvement and Research (CFH2022-1-4071); the Beijing Young Scientist Program (BJJWZYJH01201910001006); National Natural Science Foundation of China (82300764, 82130021, 72304016); Clinical Medicine Plus X - Young Scholars Project, Peking University, the Fundamental Research Funds for the Central Universities( PKU2023LCXQ002); National High Level Hospital Clinical Research Funding, Interdisciplinary Research Project of Peking University First Hospital(2023IR14, 2022CR83); Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2019-I2M-5-046) Ethics approval and consent to participate: This study was approved by the Clinical Research Ethics Committee of Peking University First Hospital (2023 620-002). Due to the retrospective nature of the study, the need for informed consent was waived by the Clinical Research Ethics Committee of Peking University First Hospital (2023 620-002). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Availability of data and material The data supporting the findings of this study are available from Peking University First Hospital. Still, restrictions apply to the availability of these data, which were used under license for the current study and are not publicly available. Data are, however, available from the corresponding author upon reasonable request and with permission of Peking University First Hospital. References Baigent C, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010;376:1670–81. Collins R, et al. 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Statin therapy may protect against acute kidney injury in patients hospitalized for interstitial SARS-CoV2 pneumonia. Nutr METABOLISM Cardiovasc Dis. 2023;33:227–31. Oh TK, et al. Preadmission Statin Therapy Is Associated with a Lower Incidence of Acute Kidney Injury in Critically Ill Patients: A Retrospective Observational Study. J Clin Med. 2019;8:25. Zheng Z, et al. Perioperative Rosuvastatin in Cardiac Surgery. N Engl J Med. 2016;374:1744–53. Cannon CP, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–504. LaRosa JC, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425–35. Rodriguez F, et al. Association of Statin Adherence With Mortality in Patients With Atherosclerotic Cardiovascular Disease. JAMA Cardiol. 2019;4:206–13. Schubert J, et al. Low-density lipoprotein cholesterol reduction and statin intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study. Eur Heart J. 2021;42:243–52. Lenihan CR, Lafayette RA. High-potency statins and acute kidney injury-associated hospitalizations. Am J Kidney Dis. 2013;62:877–9. Aalbers J. Higher statin doses linked to acute kidney injury: South African experts comment on clinical implications. Cardiovasc J Afr. 2013;24:97. Panonnummal R, Varkey J. Statins induced nephrotoxicity: a dose dependent study in albino rats. Int J Pharm Pharm Sci. 2014;6:401–6. Herrington DM, et al. Statin therapy, cardiovascular events, and total mortality in the Heart and Estrogen/Progestin Replacement Study (HERS). Circulation. 2002;105:2962–7. Papazian L, et al. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. JAMA. 2013;310:1692–700. Ridker PM, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005;352:20–8. Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380:565–71. Nakamura H, et al. Pravastatin and cardiovascular risk in moderate chronic kidney disease. ATHEROSCLEROSIS. 2009;206:512–7. Wanner C, et al. Randomized controlled trial on the efficacy and safety of atorvastatin in patients with type 2 diabetes on hemodialysis (4D study):: Demographic and baseline characteristics. Kidney Blood Press Res. 2004;27:259–66. Fellstrom BC, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360:1395–407. Herrington WG, et al. Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials. LANCET DIABETES Endocrinol. 2016;4:829–39. Additional Declarations No competing interests reported. Supplementary Files SupplementalFigure1.pdf SupplementalTable1.docx 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-4027948","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":282001522,"identity":"87d76c3d-1022-45fb-b1e5-4831efff2673","order_by":0,"name":"Xi-Zi Zheng","email":"","orcid":"","institution":"Department of Medicine, Institute of Nephrology, Peking University First Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xi-Zi","middleName":"","lastName":"Zheng","suffix":""},{"id":282001523,"identity":"a0b92483-d34d-41f0-9560-944d9594dc1b","order_by":1,"name":"Ling-Er Tang","email":"","orcid":"","institution":"Department of Medicine, Institute of Nephrology, Peking University First Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ling-Er","middleName":"","lastName":"Tang","suffix":""},{"id":282001524,"identity":"289d0cea-73e9-4cb7-8e06-744a572913cd","order_by":2,"name":"Da-Min Xu","email":"","orcid":"","institution":"Department of Medicine, Institute of Nephrology, Peking University First Hospital","correspondingAuthor":false,"prefix":"","firstName":"Da-Min","middleName":"","lastName":"Xu","suffix":""},{"id":282001525,"identity":"954b8bae-1812-4227-b5fc-c9474c603ea1","order_by":3,"name":"Ling-Yi Xu","email":"","orcid":"","institution":"Department of Medicine, Institute of Nephrology, Peking University First Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ling-Yi","middleName":"","lastName":"Xu","suffix":""},{"id":282001526,"identity":"df15121d-2f37-4afb-9955-34c45c31cbae","order_by":4,"name":"You-Lu Zhao","email":"","orcid":"","institution":"Department of Medicine, Institute of Nephrology, Peking University First Hospital","correspondingAuthor":false,"prefix":"","firstName":"You-Lu","middleName":"","lastName":"Zhao","suffix":""},{"id":282001527,"identity":"fc8fd9a0-d543-4a08-8a8b-f2a460f0678f","order_by":5,"name":"Yi-Dan Zhu","email":"","orcid":"","institution":"Clinical Research Institute, Institute of Advanced Clinical Medicine, Peking University","correspondingAuthor":false,"prefix":"","firstName":"Yi-Dan","middleName":"","lastName":"Zhu","suffix":""},{"id":282001528,"identity":"5b8931ea-e6c4-4878-8847-17fd1d94d025","order_by":6,"name":"Ji-Cheng Lv","email":"","orcid":"","institution":"Department of Medicine, Institute of Nephrology, Peking University First Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ji-Cheng","middleName":"","lastName":"Lv","suffix":""},{"id":282001529,"identity":"9452152b-1ceb-4fee-9bef-91560c3eaa59","order_by":7,"name":"Li Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYBACPmYILWfAcABEMxPWwgZVY0yCFiiduAFCE6OFnYFN4ueO2vTtjKfTJBgqrBMb2M8eIOQwNsneM8dzdzac3SbBcCY9sYEnL4GgFgnetmO5Gw4AtTC2HU5skOAxIGzL37Zj6QZgLf+I1CLN21aTANHSQJQWxmZr2bYDhkC/bLZIOJZu3MaTg18LP//hgzffttXJm0uc3XjjQ421bD/7GfxaGBgYWyQYGA4zMEgcYGBIYEDEFD7A/IGBoQ5oXwMRakfBKBgFo2BEAgDrIUGZdRNhDQAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Medicine, Institute of Nephrology, Peking University First Hospital","correspondingAuthor":true,"prefix":"","firstName":"Li","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2024-03-07 15:45:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4027948/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4027948/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53197144,"identity":"95eba560-6ec6-4afc-90b6-797cb0de429c","added_by":"auto","created_at":"2024-03-21 18:36:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":53030,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow diagram for this study selection.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4027948/v1/299607cb803469d65c20da1e.png"},{"id":53197145,"identity":"2021b696-81d7-458c-942c-11740532c241","added_by":"auto","created_at":"2024-03-21 18:36:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":72894,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSubgroup analysis in the association between statin use and acute kidney injury\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4027948/v1/eee07145644a0956bb80832b.png"},{"id":61726110,"identity":"a8960af2-7769-4b79-aea6-77ad4dadee08","added_by":"auto","created_at":"2024-08-04 18:31:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":847466,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4027948/v1/d33b7827-f7dc-43c7-b3b1-13cde3a6ef46.pdf"},{"id":53197146,"identity":"3f32c190-8d28-46ee-8590-2ffb2e5e1843","added_by":"auto","created_at":"2024-03-21 18:36:57","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":84925,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigure1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4027948/v1/e9a8529bd8d06ea4b9860cf9.pdf"},{"id":53197147,"identity":"cda93e91-a3fc-4400-97aa-9c0bdf57ffd6","added_by":"auto","created_at":"2024-03-21 18:36:57","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":37058,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4027948/v1/ff5f5466c6f4fe6b2f17219d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Statin use and in-hospital outcomes among chronic kidney disease patients: a retrospective cohort study","fulltext":[{"header":"Background","content":"\u003cp\u003eStatins are broadly prescribed for lipid management, and their cardiovascular benefits in the general population are well demonstrated by numerous high-quality trials\u003csup\u003e1\u0026ndash;4\u003c/sup\u003e. Stains were also found to reduce mortality in chronic kidney disease (CKD) and thus promoted by guidelines\u003csup\u003e5\u003c/sup\u003e. However, in clinical practice, non-adherence to the recommendation of statin use in CKD was common\u003csup\u003e6\u003c/sup\u003e because it\u0026rsquo;s difficult for clinicians to balance drug safety and efficacy in this special population with decreased kidney clearance, multiple morbidities, and comedication.\u003c/p\u003e \u003cp\u003eAcute kidney injury (AKI), the sudden loss of kidney function, is rarely reported as an adverse effect of statins in clinical trials\u003csup\u003e7\u003c/sup\u003e. However, real-world studies showed statin use contributed to the risk of AKI\u003csup\u003e8\u0026ndash;10\u003c/sup\u003e. In a cohort of 43,438 patients who were followed for up to 6.5 years, statin users were 30% more likely to develop AKI compared with non-users\u003csup\u003e11\u003c/sup\u003e. This discrepancy may be attributed to selection bias as patients at high risk of AKI (e.g. patients with advanced CKD or acute illness) may be preferably not included in clinical trials. To date, limited data has focused on the influence of statins on AKI in CKD patients, and both protective as well as detrimental effects were reported\u003csup\u003e10,12\u0026ndash;17\u003c/sup\u003e. Therefore, in this retrospective study, we aimed to investigate the impact of statin use on in-hospital outcomes in CKD patients, with in-hospital AKI being the primary outcome and in-hospital mortality as the secondary outcome.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eThis observational retrospective cohort study was conducted at the Peking University First Hospital, China. All adult hospital admissions from January 1, 2018, to December 31, 2020 were screened, and those with CKD on admission were included. CKD was defined as a baseline estimated glomerular filtration rate (eGFR)\u0026thinsp;\u0026lt;\u0026thinsp;60 ml/min.1.73m\u003csup\u003e2\u003c/sup\u003e, calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Eq.\u0026nbsp;1\u003csup\u003e8\u003c/sup\u003e using the first serum creatinine (SCr) measurement within 48 hours of admission. Patients were excluded if they (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) had a hospital stay of less than 24 hours; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) had SCr detected less than two times during hospitalization; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) had a baseline eGFR\u0026thinsp;\u0026lt;\u0026thinsp;15 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e or on dialysis; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) with admitting diagnosis of AKI; (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) developed AKI within 48 hours of admission. Only the first admission that met the criteria was included in the event of readmissions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003ePatient data were systematically collected through medical chart abstraction using the institution\u0026rsquo;s clinical data warehouse, which includes all inpatient information. The baseline was defined as 48 hours of admission. We included demographic data, chronic comorbidities, admission department, surgery information, concomitant medications, and laboratory tests. Chronic comorbidities were identified according to admission diagnosis using the International Classification of Diseases-10th revision (ICD-10) codes. Concomitant medications were determined according to prescriptions. Patients were followed up until death or discharge or 30 days after admission, whichever came first. All SCr values were recorded to identify AKI.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003eStatin exposure\u003c/h2\u003e \u003cp\u003eStatin use was defined as at least one prescription of statins within 48 hours of admission. Stain type and dose were classified by the first prescription. Statin intensity was classified into low, moderate, and high according to the American College of Cardiology/American Heart Association Guideline on the Management of Blood Cholesterol\u003csup\u003e19\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eClinical outcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome is AKI, defined as an increase in SCr by 50% or greater within 7 days or 26.5 mmol/L within 48 hours during follow-up, according to the 2012 KDIGO AKI criteria \u003csup\u003e20\u003c/sup\u003e. The secondary outcome is in-hospital mortality, defined as all causes of death during follow-up. We initially planned to explore the association between statin use and myopathic injury, defined as a raised creatine kinase concentration of four or more times the upper limit of normal. However, given that myopathic injury occurred in only a minority of the population (0.7%, 36/5376), there was insufficient statistical power to explore this hypothesis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eCategorical variables were expressed as frequencies, and Chi-square or Fisher exact test was used to compare groups. Whereas continuous variables were expressed as medians (interquartile range), non-parametric tests were used for group comparisons.\u003c/p\u003e \u003cp\u003eWe used COX proportional hazard models to estimate the hazard ratio of outcomes, adjusting for 19 prespecified covariates. Covariates were chosen based on clinical experience, related literature\u003csup\u003e13,21\u0026ndash;24\u003c/sup\u003e, and accessibility, including age, gender, body mass index, ICU admission(defined as hospitalized in ICU or transferred to ICU within 48 hours of admission), chronic comorbidities (diabetes, cardiovascular disease, cerebrovascular disease, severe liver disease, and malignancy), concomitant medications (contrast, proton pump inhibitors, renin-angiotensin-aldosterone system inhibitors, diuretics, non-steroidal anti-inflammatory drugs), and baseline laboratory tests (eGFR, hemoglobin, serum albumin, creatine kinase, and D-dimer). Multiple imputations were used to address missing values.\u003c/p\u003e \u003cp\u003eWe also conducted prespecified subgroup analyses, including age, gender, baseline eGFR, and cardiovascular disease, and considered a \u003cem\u003eP\u003c/em\u003e value less than 0.05 as a significant interaction. We initially planned to evaluate the relationship between statin intensity and outcomes. However, given that most patients (1958/2129, 92.0%) received moderate-intensity statin, there was insufficient statistical power to explore this hypothesis. Statin types were classified into atorvastatin, rosuvastatin, and other statins, as the first two are most commonly used in the study population.\u003c/p\u003e \u003cp\u003eWe performed two sensitivity analyses to examine whether potential bias could have been introduced by statin initiation/discontinuation. First, we excluded those who discontinued statins during follow-up and defined statin users as those who took statins within 48 hours of admission and continued using them during follow-up. Second, we further excluded those who initiated statins after the baseline phase and defined non-users as those who did not use statins throughout the follow-up. All analyses were performed using R software (R, version 4.2.1).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eClinical characteristics\u003c/h2\u003e \u003cp\u003eA total of 5,376 CKD patients were included in this study (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median age was 72 years, and 59.2% were male. The median baseline eGFR was 47.9 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e. Of these patients, 2,129 (39.6%) were prescribed statin within 48 hours of admission (statin users). Compared with non-users, statin users were older, more likely to have an ICU admission, and had a higher comorbidity burden except for severe liver disease and malignancy. Likewise, more frequent use of concomitant medications was also found in statin users. There was no significant difference in baseline eGFR between statin users and non-users (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \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 \u003cp\u003eBaseline characteristics of hospitalized CKD patients, categorized into statin users and non-users.\u003c/p\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\" colname=\"c2\"\u003e \u003cp\u003eAll subjects\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;5376)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStatin user\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;2129)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eStatin non-user\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;3247)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.0(61.0,81.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.0(65.0,82.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e70.0(59.0,79.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3184(59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1293(60.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1891(58.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.0(22.0,27.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.0(23.0,28.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e24.0(22.0,27.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU admission\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e462(8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e306(14.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e156(4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChronic comorbidity, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\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 \u003cp\u003eDyslipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1879(35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1493(70.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e386(11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3821(71.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1810(85.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2011(61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1965(36.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1090(51.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e875(26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiovascular disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2369(44.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1575(74.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e794(24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1064(19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e673(31.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e391(12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral vascular disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1014(18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e747(35.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e267(8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere liver disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89(1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e80(2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1147(21.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e221(10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e926(28.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eConcomitant medication, n (%)\u003c/b\u003e\u003c/p\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 \u003cp\u003eContrast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e284(5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e119(5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e165(5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.416\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProton pump inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1497(27.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e852(40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e645(19.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-statin lipid-lowering agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e199(3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e156(7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e43(1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRAAS inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1753(32.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1118(52.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e635(19.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-blockers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1380(25.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e962(45.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e418(12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiuretics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1457(27.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e901(42.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e556(17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNSAIDs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1603(29.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1247(58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e356(11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnticoagulants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1974(36.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1313(61.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e661(20.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline laboratory tests\u003c/b\u003e\u003c/p\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\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\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 \u003cp\u003eeGFR(ml/min.1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47.9(37.3,54.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.6(37.7,54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e48.0(37.0,55.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.679\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124.0(109.0,136.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e125.0(111.0,136.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e124.0(107.0,137.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum albumin(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.3(35.2,42.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.7(35.2,41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e39.8(35.2,43.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL-C(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.4(1.8,3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.1(1.6,2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.6(2.1,3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT(U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.0(11.0,22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.0(11.0,23.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e14.0(10.0,22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCK(U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.0(51.0,123.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85.0(57.0,135.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e73.0(47.0,116.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer(mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2(0.1,0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.2(0.1,0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.2(0.1,0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003e*\u003c/sup\u003e Hospitalized in ICU or transferred to ICU within 48 hours of admission.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eMissing value: Body mass index (140), hemoglobin (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e), AST (72), ALT (71), serum albumin (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e), LDL-C (743), CK (1063), D-dimer (320).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eICU, intensive care unit;RAAS inhibitors, renin-angiotensin-aldosterone system inhibitors; NSAIDs, nonsteroidal anti-inflammatory drugs; eGFR, estimated glomerular filtration rate; LDL-C, low-density lipoprotein cholesterol; ALT, alanine transaminase; AST, Aspartate transaminase; CK, creatine kinase.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eSupplemental Table\u0026nbsp;1 Sensitivity analysis of the association between statin use and primary and secondary outcome\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eAssociation between statin use and in-hospital AKI\u003c/h2\u003e \u003cp\u003eDuring 9 (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) days of follow-up, 362 in-hospital AKI were recorded. The incidence of in-hospital AKI was 7.0% (149/2129) in statin users and 6.6% (213/3247) in non-users. No significant association was found between statin use and AKI in the unadjusted model (hazard ratio [HR], 1.08; 95% CI, 0.87\u0026ndash;1.33). After adjusting for selected variables, statin use was associated with a decreased risk of AKI (aHR, 0.74; 95% CI, 0.57\u0026ndash;0.96) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The protective effect against in-hospital AKI was observed in atorvastatin (aHR 0.74; 95% CI 0.55\u0026ndash;0.99) and rosuvastatin users (aHR 0.61; 95% CI 0.38\u0026ndash;0.98) in the adjusted model (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\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 \u003cp\u003eAssociation between statin use with primary and secondary outcome in hospitalized CKD patients.\u003c/p\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo. of Patients with Event (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eHazard Ratio\u003c/p\u003e \u003cp\u003e(95% Confidence Interval)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStatin user\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStatin non-user\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUnadjusted\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdjusted \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute kidney injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e149(7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e213(6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.08(0.87,1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.74(0.57,0.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIn hospital mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17(0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56(1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.47(0.27,0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.44(0.23,0.82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e Adjusted for: age, gender, body mass index, chronic comorbidity (diabetes, cardiovascular disease, cerebrovascular disease, severe liver disease, malignancy), ICU admission, medication (contrast, proton pump inhibitor, renin-angiotensin-aldosterone system inhibitors, diuretic, non-steroidal anti-inflammatory drugs), laboratory tests (hemoglobin, serum albumin, eGFR, creatine kinase, D-dimer)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\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 \u003cp\u003eAssociation of different types of statin with primary and secondary outcome.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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=\"char\" char=\".\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eAcute kidney injury\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eIn hospital mortality\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEvents (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnadjusted\u003c/p\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdjusted\u003c/p\u003e \u003cp\u003eHR (95%CI) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEvents (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnadjusted\u003c/p\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAdjusted\u003c/p\u003e \u003cp\u003eHR (95%CI) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-users (N\u0026thinsp;=\u0026thinsp;3247)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e213(6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e56(1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtorvastatin users (N\u0026thinsp;=\u0026thinsp;1350)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e103(7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.18(0.93,1.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.74(0.55,0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12(0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.53(0.28,0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.49(0.24,1.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRosuvastatin users (N\u0026thinsp;=\u0026thinsp;453)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24(5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.80(0.52,1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.61(0.38,0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4(0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.51(0.18,1.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.49(0.17,1.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther statin users (N\u0026thinsp;=\u0026thinsp;326)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22(6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.06(0.68,1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99(0.61,1.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1(0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.19(0.03,1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.21(0.03,1.59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003ea\u003c/sup\u003e Adjusted for: age, gender, body mass index, chronic comorbidity (diabetes, cardiovascular disease, cerebrovascular disease, severe liver disease, malignancy), acute illness (ICU admission within 48 hours of admission), medication (contrast, proton pump inhibitor, renin-angiotensin-aldosterone system inhibitors, diuretic, non-steroidal anti-inflammatory drugs), laboratory tests (hemoglobin, serum albumin, eGFR, creatine kinase, D-dimer)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the associations of statin use with AKI were broadly similar among subgroups classified by age, gender, baseline eGFR, and cardiovascular disease (all \u003cem\u003eP\u003c/em\u003e for heterogeneity\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In sensitivity analysis, we evaluated the association between statin use and AKI in the population that excluded patients who discontinued statin during hospitalization (aHR, 0.69, 95%CI 0.52\u0026ndash;0.91) and in the population that further excluded patients who initiated statin after the baseline phase (aHR 0.71, 95%CI 0.53\u0026ndash;0.96); both confirmed the robustness of our conclusions (\u003cb\u003eSupplemental Table\u0026nbsp;1\u003c/b\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eAssociation between statin use and in-hospital mortality\u003c/h2\u003e \u003cp\u003eDuring 9 (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) days of follow-up, a total of 73 patients died. Statin users had a significantly lower in-hospital mortality rate than non-users (0.8% vs 1.7%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). As shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, a significant association between statin use and in-hospital mortality was observed in the unadjusted model (hazard ratio [HR], 0.47; 95% CI, 0.27\u0026ndash;0.81). After adjusting for potential confounders, the association was enhanced and remained statistically significant (aHR 0.44, 95% CI 0.23\u0026ndash;0.82). The in-hospital mortality rate was 0.9% (12/1350) in atorvastatin users, 0.9% (4/453) in rosuvastatin users, and 0.3% (1/326) in other statin users, although the association remained significant only in atorvastatin users (aHR 0.49, 95%CI 0.24-1.00) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eResults from the subgroup analysis were consistent with the main results as the associations of statin use with in-hospital mortality were broadly similar among subgroups classified by age, gender, baseline eGFR, and cardiovascular disease (all \u003cem\u003eP\u003c/em\u003e for heterogeneity\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (\u003cb\u003eSupplemental Fig.\u0026nbsp;1\u003c/b\u003e). In sensitivity analysis, statin use remained to be associated with decreased in-hospital mortality when we redefined statin users (aHR 0.28, 95%CI 0.13\u0026ndash;0.61) and further redefined non-statin users (aHR 0.24, 95%CI 0.11\u0026ndash;0.52) (\u003cb\u003eSupplemental Table\u0026nbsp;1\u003c/b\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective study of 5,376 hospitalized CKD patients, we found statin use was associated with a 26% reduction in in-hospital AKI and a 56% reduction in in-hospital mortality. These findings remained consistent in subgroup analyses stratified by age, gender, baseline eGFR, and cardiovascular disease.\u003c/p\u003e \u003cp\u003eThe protective effects of statins on cardiovascular events were fully proven in the general population\u003csup\u003e25\u0026ndash;28\u003c/sup\u003e and non-dialysis CKD patients\u003csup\u003e17,29\u0026ndash;31\u003c/sup\u003e. Therefore, the 2013 Kidney Disease Improving Global Outcomes (KDIGO) guidelines promote their use for lipid management in CKD\u003csup\u003e20\u003c/sup\u003e. Despite the evidence-based recommendation, statin under-prescribing was reported in CKD as drug safety is a major issue in this special population\u003csup\u003e6,32\u0026ndash;34\u003c/sup\u003e. AKI is a common complication in CKD patients, especially when they are hospitalized for acute illness. Unlike cardiovascular benefits, the impact of statins on AKI remains uncertain\u003csup\u003e10,12\u0026ndash;17\u003c/sup\u003e. In AKI animal models\u003csup\u003e35,36\u003c/sup\u003e, pretreatment with statins could improve the course of kidney injury via decreasing oxidation stress, ameliorating endothelial dysfunction, and reversing increased vascular permeability. Statin use was also reported to be associated with reduced incidence of AKI in different clinical scenarios (e.g., exposure to iodinated contrast agents\u003csup\u003e37\u003c/sup\u003e, surgery\u003csup\u003e22\u003c/sup\u003e, infection\u003csup\u003e38\u003c/sup\u003e, and critical condition\u003csup\u003e39\u003c/sup\u003e). Controversially, in a large clinical trial including 1,922 patients undergoing cardiac surgery, treatment with rosuvastatin was associated with an increased risk of postoperative AKI\u003csup\u003e40\u003c/sup\u003e. The excess risk of AKI among statin users was also observed in an earlier population-based cohort study of more than 2\u0026nbsp;million patients in England and Wales\u003csup\u003e9\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDifferent statin intensities might contribute to the previous inconsistent findings. Compared with moderate-intensity statins, high-intensity statins are more efficient for improving cardiovascular disease and thus are favored for high-risk patients\u003csup\u003e41\u0026ndash;44\u003c/sup\u003e. Yet a considerable body of evidence\u003csup\u003e8\u0026ndash;10,23,45\u0026ndash;47\u003c/sup\u003e proved that statins also contribute to the risk of AKI with an intensity-response effect. In our study, most patients were prescribed a moderate-intensity statin, which might relate to patient characteristics (elderly, decreased kidney function, comorbidities, and polypharmacy). That could explain why statin use showed a protective effect against AKI in hospitalized CKD patients. Our findings supported that moderate-intensity statins may be beneficial for kidney function in the presence of CKD; whether high-intensity statins have similar kidney-protective effects in CKD patients remains uncertain.\u003c/p\u003e \u003cp\u003eThe survival benefit of statins in the general population and patients with existing cardiovascular disease was fully proved by many large randomized controlled trials\u003csup\u003e48\u0026ndash;51\u003c/sup\u003e. This benefit was also evident in CKD patients. A post hoc analysis of JUPITER trial \u003csup\u003e30\u003c/sup\u003e showed that statin users experience a significant reduction in all-cause mortality (HR 0.56, 95% CI 0.37\u0026ndash;0.85) in patients with eGFR less than 60 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e. Another trial \u003csup\u003e52\u003c/sup\u003e included patients with eGFR 30-\u0026lt;60 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e also found a significant association between statin use and reduced mortality (HR 0.49, 95% CI 0.27\u0026ndash;0.89). Although SHARP study\u003csup\u003e31\u003c/sup\u003e did not find a similar reduction in mortality in CKD patients, it is worth mentioning that 1/3 of the study population was on dialysis, which may attenuate the impact of statins\u003csup\u003e53\u0026ndash;55\u003c/sup\u003e. Our findings also add to the existing evidence of the survival benefit of statins in non-dialysis CKD patients.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, due to the lack of outpatient data, the duration of preadmission statin use could not be ascertained. Second, due to the observational nature of the study, causality cannot be determined on the current design; we performed the multivariable adjustment and sensitivity analysis to lower the chances of bias, and the findings remained consistent. Third, using baseline eGFR to define CKD might capture patients with community-acquired AKI who fluctuate across the eGFR cutoff; we excluded patients with admitting diagnosis of AKI or those who developed AKI within 48 hours of admission to minimize this incorrect capture. Finally, the impact of statin intensity could not be evaluated due to insufficient statistical power.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eStatin use may not only improve survival but also protect against AKI in CKD patients. Further study is required to determine the safety and efficacy of statin intensities in this population.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAKI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute kidney injury\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ealanine transaminase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003easpartate transaminase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCK\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecreatine kinase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCKD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echronic kidney disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eeGFR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eestimated glomerular filtration rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLDL-C\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elow-density lipoprotein cholesterol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNSAIDs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enonsteroidal anti-inflammatory drug\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRAAS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erenin-angiotensin-aldosterone system\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSCr\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eserum creatinine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception, X.-Z.Z. and L.Y.; methodology and formal analysis, X.-Z.Z. and L.-E.T; investigation, X.-Z.Z.; data extraction and curation, L.-E.T., Q.-Q.Z., L.-Y.X., D.-M.X., Y.-L.Z., Y.-D.Z.; writing\u0026mdash; original draft preparation, X.-Z.Z. and L.-E.T.; writing\u0026mdash;review and editing, J.-C.L., and L.Y. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBeijing Nova Program (2021051); the Fundamental Research Funds for the Central Universities, Peking University Clinical Scientist Training Program (BMU2023PYJH023); the Capital\u0026apos;s Funds for Health Improvement and Research (CFH2022-1-4071); the Beijing Young Scientist Program (BJJWZYJH01201910001006); National Natural Science Foundation of China (82300764, 82130021, 72304016); Clinical Medicine Plus X - Young Scholars Project, Peking University, the Fundamental Research Funds for the Central Universities(\u0026nbsp;PKU2023LCXQ002); National High Level Hospital Clinical Research Funding, Interdisciplinary Research Project of Peking University First Hospital(2023IR14, 2022CR83); Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2019-I2M-5-046)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Clinical Research Ethics Committee of Peking University First Hospital (2023 620-002). Due to the retrospective nature of the study, the need for informed consent was waived by the Clinical Research Ethics Committee of Peking University First Hospital (2023 620-002).\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\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are available from Peking University First Hospital. Still, restrictions apply to the availability of these data, which were used under license for the current study and are not publicly available. Data are, however, available from the corresponding author upon reasonable request and with permission of Peking University First Hospital.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBaigent C, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010;376:1670\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollins R, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388:2532\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYusuf S, et al. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016;374:2021\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMihaylova B, et al. 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The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377:2181\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoulind MB, et al. Further perspectives on statin use in patients with chronic kidney disease. Basic Clin Pharmacol Toxicol. 2022;131:303\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJairoun AA, Ping CC, Ibrahim B. Statin therapy for patients with diabetic nephropathy: balance between safety and efficacy of statin treatment for patients with impaired kidney function. Eur Rev Med Pharmacol Sci. 2023;27:10595\u0026ndash;604.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBotshekan S, Yalameha B. Are statins toxic or safe for kidney diseases? An updated mini-review study. 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LANCET DIABETES Endocrinol. 2016;4:829\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"acute kidney injury, statin, chronic kidney disease, mortality","lastPublishedDoi":"10.21203/rs.3.rs-4027948/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4027948/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChronic kidney disease (CKD) represents a significant burden of cardiovascular disease and acute kidney injury (AKI). Statins were recommended in CKD for cardiovascular benefits, while their effect on AKI remains inconsistent.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAll adult hospital admissions between January 1, 2018, and December 31, 2020 were retrospectively screened, and CKD patients were included. Exposure was defined as any statin prescription within 48 hours of admission. Patients were followed up until death or discharge or a maximum period of up to 30 days. The primary outcome was in-hospital AKI, and the secondary outcome was in-hospital mortality.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 5,376 patients enrolled, the median age was 72 years, 3,184 (59.2%) were male, and 2,129 (39.6%) were statin users. In-hospital AKI occurred in 149(7.0%) of statin users and 213(6.6%) of non-users. Statin use was associated with a significantly decreased risk of in-hospital AKI (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI] 0.57\u0026ndash;0.96), and in-hospital mortality (aHR 0.44; 95% CI 0.23\u0026ndash;0.82). A significantly decreased risk of in-hospital AKI was observed in both atorvastatin users and rosuvastatin users. These findings remained consistent in subgroup analyses stratified by age, gender, baseline eGFR, and cardiovascular disease (All \u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eStatins may not only improve survival but also protect against AKI in CKD patients.\u003c/p\u003e","manuscriptTitle":"Statin use and in-hospital outcomes among chronic kidney disease patients: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-21 18:36:53","doi":"10.21203/rs.3.rs-4027948/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":"43588b50-4f2c-47ef-adb4-84164125a9b2","owner":[],"postedDate":"March 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-04T18:23:24+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-21 18:36:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4027948","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4027948","identity":"rs-4027948","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}