Sirtuin-1: A marker of contrast-induced nephropathy following percutaneous coronary intervention?

Sirtuin-1: A marker of contrast-induced nephropathy following percutaneous coronary intervention? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Sirtuin-1: A marker of contrast-induced nephropathy following percutaneous coronary intervention? Melis ARDIC, Cuma Bulent GUL This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4686093/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives Contrast-induced acute kidney injury (CI-AKI) is a serious complication of clinical practice after cardiac catheterization. Sirtuin-1 is a crucial regulator of the protection of the kidney against ischemia/reperfusion injury, inflammation, and vasoconstriction. In the present study, we sought to investigate whether Sirtuin-1 may be an early diagnostic marker of CIN. Methods 76 patients admitted for elective percutaneous coronary interventions (PCI) for stable angina were enrolled between July 2022 and November 2022, and 50 patients were eligible to study. Sirtuin-1 values were measured by the Elisa kit before, 24 and 72 hours after the PCI. Results There is no statistically significant difference between CI-AKI (n = 17) and non-AKI (n = 33) groups regarding Sirtuin-1 between patient samples obtained before and after PCI. Conclusions These findings refute the hypothesis that Sirtuin-1 may be clinically beneficial as a biomarker for CI-AKI following radiological procedures requiring intravascular administration of iodinated contrast media. Sirtuin-1 CI-AKI post-PCI renalism Figures Figure 1 INTRODUCTION Renalism can be defined as the fear of AKI after procedures requiring contrast media. It is very common in cardiology practice, especially after interventional procedures. It can lead to delayed procedures and, therefore, delayed diagnosis and treatment of patients [ 1 ] Several studies in recent decades have shown that contrast-induced acute kidney injury (CI-AKI), even mild and transient, is associated with an increased risk of poor outcomes, including new or progressive CKD, cardiovascular events, and mortality. Considering the burden of CI-AKI, reliable biomarkers are necessary to facilitate clinical care and accelerate the development and availability of early diagnostic tools [ 2 ]. As interventional cardiologists are increasingly called upon to perform percutaneous coronary interventions (PCIs), there is a compelling need for robust and effective markers of CI-AKI in this patient population. The precise cause of CI-AKI is not completely understood yet. The primary causes are vasoconstriction, reduced oxygen delivery, and hypoxia induced by contrast media (CM). This leads to oxidative stress and cellular death due to elevated reactive oxygen species (ROS) production, resulting in renal tubular toxicity [ 2 ]. Sirtuin 1 (SIRT1) is a class III nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase. It is a highly sensitive energy sensor [ 3 ]. SIRT1 is involved in eNOS deacetylation, increasing NO production from endothelial cells. When activated, SIRT1 enhances the resistance of renal tubular cells to oxidative stress [ 4 ]. Previous studies have shown that overexpression of SIRT-1 is protective against the effects of cisplatin-induced ischemia-reperfusion (I/R) injury [ 5 ]. In rats exposed to I/R injury by renal artery clamping, there was less tubular damage in young rats that expressed high levels of SIRT1 activity compared with older ones. In the same study, the SIRT1 activator SRT 1720 administration reduced tubular damage in SIRT-/+ rats [ 6 ]. Resveratrol, a well-known antioxidant, alleviated renal cell damage in mice by increasing SIRT1 expression in iohexol-induced CI-AKI [ 3 ]. In this preliminary study, we aimed to investigate the role of SIRT1 activation, which has previously been shown to protect the kidney from hypoxia, I/R injury, tubular toxicity, and vasoconstriction in many models, in CI-AKI caused by the same pathophysiological pathways. Our hypothesis was that patients with insufficient SIRT1 expression might develop CI-AKI, and SIRT1 could be used as a predictor of CI-AKI. METHOD Study design We conducted a case-control study using a hospital-based cohort of all patients (n = 76) admitted to Bursa Yuksek Ihtisas Training Hospital for elective PCI for stable angina between July 2022 and November 2022. Six patients were excluded from the study because they met the exclusion criteria, and ten patients were excluded because their 48-hour blood samples were not obtained. Analyses were performed on the 50 patients. The inclusion criteria were as follows: age between 18 and 75 years, indication for elective PCI, voluntary written consent for PCI, and participation in the study. Patients with N-acetylcysteine premedication, cardiogenic and septic shock, acute or chronic renal insufficiency of any cause, exposure to contrast media 48 hours before the study, and inability to give consent were excluded. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [ 6 ]. Eligible subjects should have an eGFR of 60 mL/min/1.73 m2 or greater. Study procedure Baseline characteristics were recorded, including age, gender, body mass index, and the presence of diabetes mellitus, hypertension, and dyslipidemia. Diabetes mellitus was defined as taking any glucose-lowering medication or having a fasting glucose level of 126 mg/dL or higher. Hypertension was diagnosed if the diastolic blood pressure was > 90 mm Hg and the systolic blood pressure was > 140 mm Hg in two separate measurements or if the subject had been on treatment for this condition for at least one year. A serum cholesterol level > 220 mg/dL or treatment with cholesterol-lowering drugs was considered to be dyslipidemia. Concomitant cardiac medications used were carefully recorded. Serum creatinine (sCr) levels were analyzed at 0, 24, and 72 hours after contrast exposure. For the SIRT1 assay, blood samples were collected at 0, 24, and 72 hours after contrast exposure, centrifuged at 4500 rpm for 10 minutes, and the supernatant stored at -80°C. The standard femoral artery approach was used for PCI. Each patient received 50–80 mL of a nonionic, low-osmolar contrast agent, iopromide (Ultravist 370, BAYER, Istanbul, Turkey). No specific protocols or medications were used in the study to prevent CI-AKI. Patients were advised to drink plenty of fluids, emphasizing oral intake. CI-AKI was defined as an absolute sCr increase > 0.5 mg/dL or an increase > 25% from baseline. All patients were informed of the purpose of the study, gave their informed consent, and the local ethics committee approved the protocol. Serum SIRT1 assay Collected samples were randomly ordered for biochemical analysis, and personnel blinded to case patients and controls performed the biochemical assays. Serum SIRT1 was measured using a human SIRT1 ELISA kit (SunRed Biotechnology, China). The coefficient of variation of inter-assay and intra-assay reproducibility for SIRT1 concentration is between 6 and 10% in our laboratory and is in accordance with that reported by the kit manufacturer. The measurement sensitivity is 0.306 ng/mL, and the range is 0.5–40 ng/mL. Measurements were also repeated on 10% of the randomly selected samples to confirm the reliability of the SIRT1 results. Data analysis SPSS version 21.0 (SPSS, Chicago, IL, USA) was used for all calculations. Continuous variables were tested for normal distribution using the Kolmogorov-Smirnov statistic and are expressed as mean ± SD or median with interquartile range. Parametric (Student's t-test) or non-parametric (Mann-Whitney U tests) statistical analyses were used to compare the two groups. Categorical variables were expressed as counts and percentages, and comparisons were made using the Pearson χ2 test. We hypothesized that the development of CI-AKI would significantly decrease serum SIRT1 levels. Based on previous data, a total sample size of 47 patients would be sufficient to detect a significant (p < 0.05) decrease in serum SIRT1 levels using a two-sided t-test with a power of 80%. An a priori power analysis was performed using G*Power version 3.1.9.7 [ 7 ]. A value of p < 0.05 (two-tailed) was considered statistically significant. RESULTS The general characteristics of cases and controls are presented in Table 1 . The mean age was significantly higher in the CI-AKI group compared to the non-AKI group (69 ± 10 vs. 61 ± 13, p = 0.038). Other clinical and pharmacological characteristics did not differ significantly between the two groups. In our cohort, the diabetes rate was 40%, and the hypertension rate was 64%. SIRT1 and sCr levels are presented in Table 2 . Initial sCr and SIRT1 levels were not different between the two groups. As expected, sCr levels increased significantly in the group at 24 and 72 hours (1.11 ± 0.29 and 1.55 ± 0.62 mg/dL, p = 0.015 and p = 0.0001, respectively). SIRT1 trends and levels in patients are shown in Fig. 1 . There was a decreasing trend in SIRT1 levels in the CI-AKI group between pre-PCI and post-PCI. However, this did not reach statistical significance. C-reactive protein concentrations tended to be higher in the group that developed CI-AKI (7.26 mg/dL vs. 18.0 mg/dL, p = 0.267, respectively). Table 3 shows the serum biochemical values of the patients. Table 1 General characteristics of patients Without AKI (n = 33) With CI-AKI (n = 17) p Age(years) 61±(13) 69± (10) 0.038 Female gender [n (%)] 10(30) 7(41) 0.534 Diabetes [n (%)] 13(40) 7(41) 0.904 Hypertension [n (%)] 18(55) 14(82) 0.550 RAS Blocker 10 (30,3) 8 (47,1) 0.242 Beta-blocker 13 (39,4) 7 (41,2) 0.903 Calcium Channel Blocker 5 (15,2) 6 (35,3) 0.151 Statins 4 (12,1) 4 (23,5) 0.419 Aspirin 11 (33,3) 7 (41,2) 0.585 Clopidogrel 6 (18,2) 1 (5,9) 0.398 SGLT2-i 1 (3,0) 2 (11,8) 0.264 p values were calculated with the χ2 test or the Student's t-test, as appropriate. Table 2 SIRT-1 and serum creatinine values in patients with and without CI-AKI Without AKI (n = 33) With CI-AKI (n = 17) Mean ± (SD) Mean ± (SD) SIRT-1 (0. hour) 5.15 ± (2.87) 5.55 ± (2.08) SIRT-1 (24. hour) 5.27 ± (3.21) 5.17 ± (1.90) SIRT-1 (72. hour) 5.52 ± (3.75) 4.84 ± (1.68) sCr (0. hour) 0.89 ± (0.18) 0.96 ± (0.21) sCr (24. hour) 0.89 ± (0.21) 1.11 ± (0.29) sCr (72. hour) 0.91 ± (0.18) 1.55 ± (0.62) SIRT-1; sirtuin-1, sCr; serum creatinine, SD; standard deviation Table 3 Biochemical values of the patients. Without AKI (n = 33) Mean±(SD) With CI-AKI (n = 17) Mean±(SD) p CRP (mg/dL) 7.26 ± (6.56) 18 ± (36.96) 0.267 Cholesterol (mg/dL) 196 ± (42) 199 ± (55) 0.845 HDL (mg/dL) 41 ± (10) 45 ± (16) 0.363 LDL (mg/dL) 125 ± (30) 132 ± (50) 0.647 Triglyceride (mg/dL) 160 ± (116) 127 ± (90) 0.285 TSH (uIU/mL) 1.10 ± (0.87) 1.95 ± (2.48) 0.249 Hgb (g/dL) 13.21± (1.86) 13.15 ± (2.14) 0.927 WBC (10 3 /mL) 11.12 ± (2.95) 11.39 ± (5.50) 0.824 Troponin I (ng/L) 22,42 ± (72,66) 4.17 ± (8.65) 0.319 CRP; C reactive protein, HDL; high-density lipoprotein, LDL; low-density lipoprotein, TSH; thyroid stimulating hormone, Hgb; hemoglobin, WBC; white blood cells. p values were calculated with the Mann-Whitney U or the Student's t-test, as appropriate. DISCUSSION Serum creatinine is currently considered a poor marker of acute kidney injury, albeit routinely used in clinical practice and clinical trials. Serum SIRT1 is easily measured by commercial ELISA kits, and the availability of commercial kits may significantly accelerate the development of the test for routine clinical use. Unfortunately, contrary to our hypothesis, the development of CI-AKI after PCI did not significantly alter serum SIRT1 levels in either the early or late phases of CI-AKI. The true incidence of CI-AKI is difficult to assess because of the wide variation in reported rates, depending on the definitions of AKI, and the patient populations studied, which have varying baseline risk factors. Rates as low as less than 1% have been reported in patient populations with no risk factors and as high as more than 20% in patients with multiple risk factors. However, CI-AKI seems slightly more common after PCI [ 2 ]. In post-PCI patients, Moitinho et al. reported a CI-AKI rate of 37.5% [ 8 ]. Our cohort has a CI-AKI rate of 34%, which is in line with the literature. I/R injury plays a major role in the development of AKI. Apoptosis of tubular epithelial cells (TECs) in I/R injury is observed in almost all AKI patients. SIRT1 may prevent I/R injury-induced damage. Gong et al. [ 9 ] found a significant increase in SIRT1 levels in human proximal cell (HK2) cells with hypoxia. In the same study in vivo phase, resveratrol, a potent activator of SIRT1, successfully reversed I/R-induced TEC apoptosis in rats. Contrast media cause local hypoxia and hypertonicity, leading to extreme oxidative stress in the renal medulla. Sirt1 is highly expressed in the renal medulla. He et al. [ 4 ] found a significant increase in SIRT1 in renal medullary interstitial cells (RMICs) of mice exposed to oxidative stress with H2O2. However, this increase was not observed in SIRT knockout mice, and increased cell apoptosis was observed in SIRT knockout mice. When these mice were exposed to the SIRT1 inducer SRT2183, cell viability increased. In our study, the group that did not develop AKI had higher levels of SIRT1. This suggests that high serum SIRT1 levels may have a protective effect against CI-AKI. Inflammation is another important mechanism involved in developing CI-AKI [ 10 ]. SIRT1 is one of the key players in the process of limiting the inflammatory response [ 11 ]. SIRT1 exerts potent anti-inflammatory activity in various cell types by inhibiting NF-κB activation [ 12 ]. SIRT1 also regulates inflammation by deacetylating high-mobility group box 1 (HMGB1), a conserved structural chromatin protein. Deletion of SIRT1 increases HMGB1 acetylation, leading to systemic inflammation [ 12 ]. Activation of SIRT1 and SIRT3 can also reduce TNF production during acute inflammation [ 13 ]. Our study showed increased levels of CRP, an indicator of inflammation, in the CI-AKI group. However, the results were not statistically significant. Nevertheless, this finding may be considered as an increase in inflammation in the CI-AKI group. SIRT1 regulates endothelium-dependent vasodilation and vascular tone via eNOS deacetylation [ 14 ]. Acute vasoconstriction due to contrast media is an important cause of CI-AKI [ 2 ]. This leads to hypoxia, particularly in the poorly perfused renal medulla. As mentioned above, SIRT1 protects against hypoxic damage and is mainly expressed in the inner medulla of the kidney [ 14 ]. In summary, numerous models of AKI induced by I/R injury and inflammation with high levels of SIRT1 have been shown to play a protective role against the development of AKI [ 3 – 5 , 9 , 14 – 16 ]. We hypothesized that SIRT1 levels would increase due to high hypertonicity and tubular toxicity after contrast exposure during PCI to protect the renal medulla from I/R injury, vasoconstriction, and inflammation. Patients with an insufficient increase in SIRT1 would develop CI-AKI. Thus, an insufficient increase in SIRT1 may be useful as a predictor of CI-AKI after PCI. In our preliminary study, serum SIRT1 tended to be lower at 24 and 72 hours after PCI, albeit this did not reach statistical significance. Although a larger sample size and more frequent measurements might have yielded favorable results, the significant change in serum creatinine levels in the CI-AKI patients provides confidence that our research methodology can detect meaningful changes in renal function. Furthermore, as all patients were selected from a single institution, we can be confident that our negative results are not due to sample variability. We conclude that the usefulness of serum SIRT1 as a diagnostic tool for CI-AKI is likely to be minimal, albeit insignificant. Abbreviations AKI: Acute Kidney Injury CI-AKI: Contrast-Induced Acute Kidney Injury CKD: Chronic Kidney Disease CM: Contrast Media CRP: C-Reactive Protein eGFR: Estimated Glomerular Filtration Rate ELISA: Enzyme-Linked Immunosorbent Assay HMGB1: High-Mobility Group Box 1 I/R: Ischemia/Reperfusion NAD+: Nicotinamide Adenine Dinucleotide PCI: Percutaneous Coronary Intervention RMICs: Renal Medullary Interstitial Cells ROS: Reactive Oxygen Species sCr: Serum Creatinine SD: Standard Deviation SIRT1: Sirtuin-1 SPSS: Statistical Package for the Social Sciences Declarations Acknowledgments The hospital authorities provided SIRT-1 kits. We appreciate the help of the interventional cardiology team during the study. Author contributions CBG provided supervision, provided statistical analysis, and wrote the manuscript; MA collated the raw data and reviewed and substantially revised the manuscript. Funding No funding declarations. Data availability Access to all anonymized data is available to the corresponding author. Corresponding author Correspondence to Cuma Bülent GUL Ethics approval and consent to participate The study protocol was approved by the Ethics Committee of Bursa Yuksek Ihtisas. All participants signed an informed consent form. Consent for publication All authors consent to the publication of this paper. Competing interests All authors have no competing interests to declare. References Chertow GM, Normand SLT, McNeil BJ. “Renalism”: Inappropriately low rates of coronary angiography in elderly individuals with renal insufficiency. Journal of the American Society of Nephrology. 2004;15:2462–8. Vemireddy L, Bansal S. Contrast-Associated Acute Kidney Injury: Definitions, Epidemiology, Pathophysiology, and Implications. Interv Cardiol Clin [Internet]. 2023 [cited 2024 Mar 11];12:489–98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/37673493 Hong YA, Bae SY, Ahn SY, Kim J, Kwon YJ, Jung WY, et al. Resveratrol Ameliorates Contrast Induced Nephropathy Through the Activation of SIRT1-PGC-1α-Foxo1 Signaling in Mice. Kidney Blood Press Res [Internet]. 2017 [cited 2024 Mar 12];42:641–53. Available from: https://pubmed.ncbi.nlm.nih.gov/29035878/ He W, Wang Y, Zhang MZ, You L, Davis LS, Fan H, et al. Sirt1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest [Internet]. 2010 [cited 2024 Mar 19];120:1056–68. Available from: https://pubmed.ncbi.nlm.nih.gov/20335659/ Sakao Y, Kato A, Tsuji T, Yasuda H, Togawa A, Fujigaki Y, et al. Cisplatin induces Sirt1 in association with histone deacetylation and increased Werner syndrome protein in the kidney. Clin Exp Nephrol [Internet]. 2011 [cited 2024 Mar 12];15:363–72. Available from: https://pubmed.ncbi.nlm.nih.gov/21416250/ Levey AS, Stevens LA, Schmid CH, Zhang Y, Castro AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12. Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods [Internet]. 2007 [cited 2024 Apr 3];39:175–91. Available from: https://pubmed.ncbi.nlm.nih.gov/17695343/ Moitinho MS, Silva Junior JR Da, Cunha MDB, Barbosa DA, Caixeta AM, Pimpinato AG, et al. Contrast-induced acute kidney injury in patients submitted to coronary angioplasty: prospective cohort. Rev Esc Enferm USP [Internet]. 2022 [cited 2024 Mar 22];56. Available from: https://pubmed.ncbi.nlm.nih.gov/35781323/ Gong L, He J, Sun X, Li L, Zhang X, Gan H. Activation of sirtuin1 protects against ischemia/reperfusion-induced acute kidney injury. Biomedicine and Pharmacotherapy. 2020;125. Chaudhari H, Mahendrakar S, Baskin SE, Reddi AS. Contrast-Induced Acute Kidney Injury: Evidence in Support of Its Existence and a Review of Its Pathogenesis and Management. Int J Nephrol Renovasc Dis [Internet]. 2022 [cited 2024 Mar 11];15:253–66. Available from: https://www.tandfonline.com/action/journalInformation?journalCode=dnrd20 Perico L, Remuzzi G, Benigni A. Sirtuins in kidney health and disease. Nat Rev Nephrol [Internet]. 2024; Available from: https://www.nature.com/articles/s41581-024-00806-4 Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A. Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal [Internet]. 2013 [cited 2024 Mar 29];25:1939–48. Available from: https://pubmed.ncbi.nlm.nih.gov/23770291/ Wu QJ, Zhang TN, Chen HH, Yu XF, Lv J Le, Liu YY, et al. The sirtuin family in health and disease. Signal Transduction and Targeted Therapy 2022 7:1 [Internet]. 2022 [cited 2024 Mar 29];7:1–74. Available from: https://www.nature.com/articles/s41392-022-01257-8 He W, Wang Y, Zhang MZ, You L, Davis LS, Fan H, et al. Sirt1 activation protects the mouse renal medulla from oxidative injury. Journal of Clinical Investigation. 2010;120:1056–68. Funk JA, Schnellmann RG. Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1α activation following ischemia-reperfusion injury. Toxicol Appl Pharmacol. 2013;273:345–54. Fan H, Yang HC, You L, Wang YY, He WJ, Hao CM. The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury. Kidney Int [Internet]. 2013 [cited 2024 Mar 19];83:404–13. Available from: https://pubmed.ncbi.nlm.nih.gov/23302720/ Additional Declarations No competing interests reported. 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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-4686093","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":335211542,"identity":"ae98b254-49eb-4ba6-a8fc-46b8aed16dc6","order_by":0,"name":"Melis ARDIC","email":"","orcid":"","institution":"Bursa Yuksek Ihtisas Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Melis","middleName":"","lastName":"ARDIC","suffix":""},{"id":335211544,"identity":"042014db-7501-400d-a0a6-353b4651cf20","order_by":1,"name":"Cuma Bulent GUL","email":"data:image/png;base64,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","orcid":"","institution":"Uludag University Faculty of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Cuma","middleName":"Bulent","lastName":"GUL","suffix":""}],"badges":[],"createdAt":"2024-07-04 11:06:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4686093/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4686093/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62190470,"identity":"0e47f802-b70b-457d-a31a-ed19ec0a0a7e","added_by":"auto","created_at":"2024-08-10 12:27:56","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":270881,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in serum SIRT-1 levels before 24 and 72 h in patients who developed CI-AKI after PCI (n = 17). There were no significant differences between pre-and post-procedural values (all\u003cem\u003e p\u003c/em\u003e values \u0026gt;0.05).\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4686093/v1/c4f617b02012e5e25b122520.jpeg"},{"id":64942007,"identity":"9f4a5c78-878a-4d85-9658-868c9d3c7c34","added_by":"auto","created_at":"2024-09-20 15:53:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":667545,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4686093/v1/12046c53-92e2-46fa-85bd-b9c20daa8dbc.pdf"},{"id":62190469,"identity":"5d973b2a-e8a0-4ceb-a342-e40b03629f10","added_by":"auto","created_at":"2024-08-10 12:27:56","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15459,"visible":true,"origin":"","legend":"","description":"","filename":"Whatisnew.docx","url":"https://assets-eu.researchsquare.com/files/rs-4686093/v1/b9a39381013be1f1db5eee0c.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sirtuin-1: A marker of contrast-induced nephropathy following percutaneous coronary intervention?","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eRenalism can be defined as the fear of AKI after procedures requiring contrast media. It is very common in cardiology practice, especially after interventional procedures. It can lead to delayed procedures and, therefore, delayed diagnosis and treatment of patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Several studies in recent decades have shown that contrast-induced acute kidney injury (CI-AKI), even mild and transient, is associated with an increased risk of poor outcomes, including new or progressive CKD, cardiovascular events, and mortality. Considering the burden of CI-AKI, reliable biomarkers are necessary to facilitate clinical care and accelerate the development and availability of early diagnostic tools [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. As interventional cardiologists are increasingly called upon to perform percutaneous coronary interventions (PCIs), there is a compelling need for robust and effective markers of CI-AKI in this patient population. The precise cause of CI-AKI is not completely understood yet. The primary causes are vasoconstriction, reduced oxygen delivery, and hypoxia induced by contrast media (CM). This leads to oxidative stress and cellular death due to elevated reactive oxygen species (ROS) production, resulting in renal tubular toxicity [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSirtuin 1 (SIRT1) is a class III nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase. It is a highly sensitive energy sensor [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. SIRT1 is involved in eNOS deacetylation, increasing NO production from endothelial cells. When activated, SIRT1 enhances the resistance of renal tubular cells to oxidative stress [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Previous studies have shown that overexpression of SIRT-1 is protective against the effects of cisplatin-induced ischemia-reperfusion (I/R) injury [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In rats exposed to I/R injury by renal artery clamping, there was less tubular damage in young rats that expressed high levels of SIRT1 activity compared with older ones. In the same study, the SIRT1 activator SRT 1720 administration reduced tubular damage in SIRT-/+ rats [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Resveratrol, a well-known antioxidant, alleviated renal cell damage in mice by increasing SIRT1 expression in iohexol-induced CI-AKI [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this preliminary study, we aimed to investigate the role of SIRT1 activation, which has previously been shown to protect the kidney from hypoxia, I/R injury, tubular toxicity, and vasoconstriction in many models, in CI-AKI caused by the same pathophysiological pathways. Our hypothesis was that patients with insufficient SIRT1 expression might develop CI-AKI, and SIRT1 could be used as a predictor of CI-AKI.\u003c/p\u003e"},{"header":"METHOD","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eWe conducted a case-control study using a hospital-based cohort of all patients (n\u0026thinsp;=\u0026thinsp;76) admitted to Bursa Yuksek Ihtisas Training Hospital for elective PCI for stable angina between July 2022 and November 2022. Six patients were excluded from the study because they met the exclusion criteria, and ten patients were excluded because their 48-hour blood samples were not obtained. Analyses were performed on the 50 patients. The inclusion criteria were as follows: age between 18 and 75 years, indication for elective PCI, voluntary written consent for PCI, and participation in the study. Patients with N-acetylcysteine premedication, cardiogenic and septic shock, acute or chronic renal insufficiency of any cause, exposure to contrast media 48 hours before the study, and inability to give consent were excluded. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Eligible subjects should have an eGFR of 60 mL/min/1.73 m2 or greater.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy procedure\u003c/h2\u003e \u003cp\u003eBaseline characteristics were recorded, including age, gender, body mass index, and the presence of diabetes mellitus, hypertension, and dyslipidemia. Diabetes mellitus was defined as taking any glucose-lowering medication or having a fasting glucose level of 126 mg/dL or higher. Hypertension was diagnosed if the diastolic blood pressure was \u0026gt;\u0026thinsp;90 mm Hg and the systolic blood pressure was \u0026gt;\u0026thinsp;140 mm Hg in two separate measurements or if the subject had been on treatment for this condition for at least one year. A serum cholesterol level\u0026thinsp;\u0026gt;\u0026thinsp;220 mg/dL or treatment with cholesterol-lowering drugs was considered to be dyslipidemia. Concomitant cardiac medications used were carefully recorded. Serum creatinine (sCr) levels were analyzed at 0, 24, and 72 hours after contrast exposure. For the SIRT1 assay, blood samples were collected at 0, 24, and 72 hours after contrast exposure, centrifuged at 4500 rpm for 10 minutes, and the supernatant stored at -80\u0026deg;C.\u003c/p\u003e \u003cp\u003eThe standard femoral artery approach was used for PCI. Each patient received 50\u0026ndash;80 mL of a nonionic, low-osmolar contrast agent, iopromide (Ultravist 370, BAYER, Istanbul, Turkey). No specific protocols or medications were used in the study to prevent CI-AKI. Patients were advised to drink plenty of fluids, emphasizing oral intake.\u003c/p\u003e \u003cp\u003eCI-AKI was defined as an absolute sCr increase\u0026thinsp;\u0026gt;\u0026thinsp;0.5 mg/dL or an increase\u0026thinsp;\u0026gt;\u0026thinsp;25% from baseline. All patients were informed of the purpose of the study, gave their informed consent, and the local ethics committee approved the protocol.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eSerum SIRT1 assay\u003c/b\u003e\u003c/h2\u003e \u003cp\u003eCollected samples were randomly ordered for biochemical analysis, and personnel blinded to case patients and controls performed the biochemical assays. Serum SIRT1 was measured using a human SIRT1 ELISA kit (SunRed Biotechnology, China). The coefficient of variation of inter-assay and intra-assay reproducibility for SIRT1 concentration is between 6 and 10% in our laboratory and is in accordance with that reported by the kit manufacturer. The measurement sensitivity is 0.306 ng/mL, and the range is 0.5\u0026ndash;40 ng/mL. Measurements were also repeated on 10% of the randomly selected samples to confirm the reliability of the SIRT1 results.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eSPSS version 21.0 (SPSS, Chicago, IL, USA) was used for all calculations. Continuous variables were tested for normal distribution using the Kolmogorov-Smirnov statistic and are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median with interquartile range. Parametric (Student's t-test) or non-parametric (Mann-Whitney U tests) statistical analyses were used to compare the two groups. Categorical variables were expressed as counts and percentages, and comparisons were made using the Pearson χ2 test. We hypothesized that the development of CI-AKI would significantly decrease serum SIRT1 levels. Based on previous data, a total sample size of 47 patients would be sufficient to detect a significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) decrease in serum SIRT1 levels using a two-sided t-test with a power of 80%. An a priori power analysis was performed using G*Power version 3.1.9.7 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A value of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 (two-tailed) was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe general characteristics of cases and controls are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age was significantly higher in the CI-AKI group compared to the non-AKI group (69\u0026thinsp;\u0026plusmn;\u0026thinsp;10 vs. 61\u0026thinsp;\u0026plusmn;\u0026thinsp;13, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.038). Other clinical and pharmacological characteristics did not differ significantly between the two groups. In our cohort, the diabetes rate was 40%, and the hypertension rate was 64%. SIRT1 and sCr levels are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Initial sCr and SIRT1 levels were not different between the two groups. As expected, sCr levels increased significantly in the group at 24 and 72 hours (1.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29 and 1.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62 mg/dL, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015 and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001, respectively). SIRT1 trends and levels in patients are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There was a decreasing trend in SIRT1 levels in the CI-AKI group between pre-PCI and post-PCI. However, this did not reach statistical significance. C-reactive protein concentrations tended to be higher in the group that developed CI-AKI (7.26 mg/dL vs. 18.0 mg/dL, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.267, respectively). Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the serum biochemical values of the patients.\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\u003eGeneral characteristics of patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\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\u003eWithout AKI (n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWith CI-AKI (n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61\u0026plusmn;(13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69\u0026plusmn; (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale gender [n (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.534\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes [n (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.904\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension [n (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.550\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRAS Blocker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (30,3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (47,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.242\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBeta-blocker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (39,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (41,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.903\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCalcium Channel Blocker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (15,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (35,3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStatins\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (12,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (23,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (33,3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (41,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.585\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClopidogrel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (18,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5,9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.398\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSGLT2-i\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3,0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (11,8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.264\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003ep\u003c/em\u003e values were calculated with the χ2 test or the Student's t-test, as appropriate.\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=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSIRT-1 and serum creatinine values in patients with and without CI-AKI\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\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eWithout AKI (n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eWith CI-AKI (n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eMean \u0026plusmn; (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMean \u0026plusmn; (SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSIRT-1 (0. hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026plusmn; (2.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026plusmn; (2.08)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSIRT-1 (24. hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026plusmn; (3.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026plusmn; (1.90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSIRT-1 (72. hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026plusmn; (3.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026plusmn; (1.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esCr (0. hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026plusmn; (0.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026plusmn; (0.21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esCr (24. hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026plusmn; (0.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026plusmn; (0.29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esCr (72. hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026plusmn; (0.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026plusmn; (0.62)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eSIRT-1; sirtuin-1, sCr; serum creatinine, SD; standard deviation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\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\u003eBiochemical values of the patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\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\u003eWithout AKI (n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003cp\u003eMean\u0026plusmn;(SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWith CI-AKI (n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003cp\u003eMean\u0026plusmn;(SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e7.26 \u0026plusmn; (6.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e18 \u0026plusmn; (36.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.267\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholesterol (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e196 \u0026plusmn; (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e199 \u0026plusmn; (55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.845\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e41 \u0026plusmn; (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e45 \u0026plusmn; (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.363\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e125 \u0026plusmn; (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e132 \u0026plusmn; (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.647\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTriglyceride (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e160 \u0026plusmn; (116)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e127 \u0026plusmn; (90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.285\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH (uIU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.10 \u0026plusmn; (0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.95 \u0026plusmn; (2.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.249\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHgb (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e13.21\u0026plusmn; (1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e13.15 \u0026plusmn; (2.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.927\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (10\u003csup\u003e3\u003c/sup\u003e/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e11.12 \u0026plusmn; (2.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e11.39 \u0026plusmn; (5.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.824\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTroponin I (ng/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e22,42 \u0026plusmn; (72,66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.17 \u0026plusmn; (8.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.319\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCRP; C reactive protein, HDL; high-density lipoprotein, LDL; low-density lipoprotein, TSH; thyroid stimulating hormone, Hgb; hemoglobin, WBC; white blood cells. \u003cem\u003ep\u003c/em\u003e values were calculated with the Mann-Whitney U or the Student's t-test, as appropriate.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eSerum creatinine is currently considered a poor marker of acute kidney injury, albeit routinely used in clinical practice and clinical trials. Serum SIRT1 is easily measured by commercial ELISA kits, and the availability of commercial kits may significantly accelerate the development of the test for routine clinical use. Unfortunately, contrary to our hypothesis, the development of CI-AKI after PCI did not significantly alter serum SIRT1 levels in either the early or late phases of CI-AKI.\u003c/p\u003e \u003cp\u003eThe true incidence of CI-AKI is difficult to assess because of the wide variation in reported rates, depending on the definitions of AKI, and the patient populations studied, which have varying baseline risk factors. Rates as low as less than 1% have been reported in patient populations with no risk factors and as high as more than 20% in patients with multiple risk factors. However, CI-AKI seems slightly more common after PCI [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In post-PCI patients, Moitinho et al. reported a CI-AKI rate of 37.5% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Our cohort has a CI-AKI rate of 34%, which is in line with the literature.\u003c/p\u003e \u003cp\u003eI/R injury plays a major role in the development of AKI. Apoptosis of tubular epithelial cells (TECs) in I/R injury is observed in almost all AKI patients. SIRT1 may prevent I/R injury-induced damage. Gong et al. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] found a significant increase in SIRT1 levels in human proximal cell (HK2) cells with hypoxia. In the same study in vivo phase, resveratrol, a potent activator of SIRT1, successfully reversed I/R-induced TEC apoptosis in rats. Contrast media cause local hypoxia and hypertonicity, leading to extreme oxidative stress in the renal medulla. Sirt1 is highly expressed in the renal medulla. He et al. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] found a significant increase in SIRT1 in renal medullary interstitial cells (RMICs) of mice exposed to oxidative stress with H2O2. However, this increase was not observed in SIRT knockout mice, and increased cell apoptosis was observed in SIRT knockout mice. When these mice were exposed to the SIRT1 inducer SRT2183, cell viability increased. In our study, the group that did not develop AKI had higher levels of SIRT1. This suggests that high serum SIRT1 levels may have a protective effect against CI-AKI.\u003c/p\u003e \u003cp\u003eInflammation is another important mechanism involved in developing CI-AKI [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. SIRT1 is one of the key players in the process of limiting the inflammatory response [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. SIRT1 exerts potent anti-inflammatory activity in various cell types by inhibiting NF-κB activation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. SIRT1 also regulates inflammation by deacetylating high-mobility group box 1 (HMGB1), a conserved structural chromatin protein. Deletion of SIRT1 increases HMGB1 acetylation, leading to systemic inflammation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Activation of SIRT1 and SIRT3 can also reduce TNF production during acute inflammation [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Our study showed increased levels of CRP, an indicator of inflammation, in the CI-AKI group. However, the results were not statistically significant. Nevertheless, this finding may be considered as an increase in inflammation in the CI-AKI group.\u003c/p\u003e \u003cp\u003eSIRT1 regulates endothelium-dependent vasodilation and vascular tone via eNOS deacetylation [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Acute vasoconstriction due to contrast media is an important cause of CI-AKI [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This leads to hypoxia, particularly in the poorly perfused renal medulla. As mentioned above, SIRT1 protects against hypoxic damage and is mainly expressed in the inner medulla of the kidney [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn summary, numerous models of AKI induced by I/R injury and inflammation with high levels of SIRT1 have been shown to play a protective role against the development of AKI [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. We hypothesized that SIRT1 levels would increase due to high hypertonicity and tubular toxicity after contrast exposure during PCI to protect the renal medulla from I/R injury, vasoconstriction, and inflammation. Patients with an insufficient increase in SIRT1 would develop CI-AKI. Thus, an insufficient increase in SIRT1 may be useful as a predictor of CI-AKI after PCI. In our preliminary study, serum SIRT1 tended to be lower at 24 and 72 hours after PCI, albeit this did not reach statistical significance. Although a larger sample size and more frequent measurements might have yielded favorable results, the significant change in serum creatinine levels in the CI-AKI patients provides confidence that our research methodology can detect meaningful changes in renal function. Furthermore, as all patients were selected from a single institution, we can be confident that our negative results are not due to sample variability. We conclude that the usefulness of serum SIRT1 as a diagnostic tool for CI-AKI is likely to be minimal, albeit insignificant.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAKI: Acute Kidney Injury\u003c/p\u003e\n\u003cp\u003eCI-AKI: Contrast-Induced Acute Kidney Injury\u003c/p\u003e\n\u003cp\u003eCKD: Chronic Kidney Disease\u003c/p\u003e\n\u003cp\u003eCM: Contrast Media\u003c/p\u003e\n\u003cp\u003eCRP: C-Reactive Protein\u003c/p\u003e\n\u003cp\u003eeGFR: Estimated Glomerular Filtration Rate\u003c/p\u003e\n\u003cp\u003eELISA: Enzyme-Linked Immunosorbent Assay\u003c/p\u003e\n\u003cp\u003eHMGB1: High-Mobility Group Box 1\u003c/p\u003e\n\u003cp\u003eI/R: Ischemia/Reperfusion\u003c/p\u003e\n\u003cp\u003eNAD+: Nicotinamide Adenine Dinucleotide\u003c/p\u003e\n\u003cp\u003ePCI: Percutaneous Coronary Intervention\u003c/p\u003e\n\u003cp\u003eRMICs: Renal Medullary Interstitial Cells\u003c/p\u003e\n\u003cp\u003eROS: Reactive Oxygen Species\u003c/p\u003e\n\u003cp\u003esCr: Serum Creatinine\u003c/p\u003e\n\u003cp\u003eSD: Standard Deviation\u003c/p\u003e\n\u003cp\u003eSIRT1: Sirtuin-1\u003c/p\u003e\n\u003cp\u003eSPSS: Statistical Package for the Social Sciences\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe hospital authorities provided SIRT-1 kits. We appreciate the help of the interventional cardiology team during the study.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCBG provided supervision, provided statistical analysis, and wrote the manuscript; MA collated the raw data and reviewed and substantially revised the manuscript. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding declarations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccess to all anonymized data is available to the corresponding author.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to Cuma B\u0026uuml;lent GUL\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Ethics Committee of Bursa Yuksek Ihtisas. All participants signed an informed consent form.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors consent to the publication of this paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have no competing interests to declare.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChertow GM, Normand SLT, McNeil BJ. \u0026ldquo;Renalism\u0026rdquo;: Inappropriately low rates of coronary angiography in elderly individuals with renal insufficiency. Journal of the American Society of Nephrology. 2004;15:2462\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eVemireddy L, Bansal S. Contrast-Associated Acute Kidney Injury: Definitions, Epidemiology, Pathophysiology, and Implications. Interv Cardiol Clin [Internet]. 2023 [cited 2024 Mar 11];12:489\u0026ndash;98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/37673493\u003c/li\u003e\n\u003cli\u003eHong YA, Bae SY, Ahn SY, Kim J, Kwon YJ, Jung WY, et al. Resveratrol Ameliorates Contrast Induced Nephropathy Through the Activation of SIRT1-PGC-1\u0026alpha;-Foxo1 Signaling in Mice. Kidney Blood Press Res [Internet]. 2017 [cited 2024 Mar 12];42:641\u0026ndash;53. Available from: https://pubmed.ncbi.nlm.nih.gov/29035878/\u003c/li\u003e\n\u003cli\u003eHe W, Wang Y, Zhang MZ, You L, Davis LS, Fan H, et al. Sirt1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest [Internet]. 2010 [cited 2024 Mar 19];120:1056\u0026ndash;68. Available from: https://pubmed.ncbi.nlm.nih.gov/20335659/\u003c/li\u003e\n\u003cli\u003eSakao Y, Kato A, Tsuji T, Yasuda H, Togawa A, Fujigaki Y, et al. Cisplatin induces Sirt1 in association with histone deacetylation and increased Werner syndrome protein in the kidney. Clin Exp Nephrol [Internet]. 2011 [cited 2024 Mar 12];15:363\u0026ndash;72. Available from: https://pubmed.ncbi.nlm.nih.gov/21416250/\u003c/li\u003e\n\u003cli\u003eLevey AS, Stevens LA, Schmid CH, Zhang Y, Castro AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604\u0026ndash;12. \u003c/li\u003e\n\u003cli\u003eFaul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods [Internet]. 2007 [cited 2024 Apr 3];39:175\u0026ndash;91. Available from: https://pubmed.ncbi.nlm.nih.gov/17695343/\u003c/li\u003e\n\u003cli\u003eMoitinho MS, Silva Junior JR Da, Cunha MDB, Barbosa DA, Caixeta AM, Pimpinato AG, et al. Contrast-induced acute kidney injury in patients submitted to coronary angioplasty: prospective cohort. Rev Esc Enferm USP [Internet]. 2022 [cited 2024 Mar 22];56. Available from: https://pubmed.ncbi.nlm.nih.gov/35781323/\u003c/li\u003e\n\u003cli\u003eGong L, He J, Sun X, Li L, Zhang X, Gan H. Activation of sirtuin1 protects against ischemia/reperfusion-induced acute kidney injury. Biomedicine and Pharmacotherapy. 2020;125. \u003c/li\u003e\n\u003cli\u003eChaudhari H, Mahendrakar S, Baskin SE, Reddi AS. Contrast-Induced Acute Kidney Injury: Evidence in Support of Its Existence and a Review of Its Pathogenesis and Management. Int J Nephrol Renovasc Dis [Internet]. 2022 [cited 2024 Mar 11];15:253\u0026ndash;66. Available from: https://www.tandfonline.com/action/journalInformation?journalCode=dnrd20\u003c/li\u003e\n\u003cli\u003ePerico L, Remuzzi G, Benigni A. Sirtuins in kidney health and disease. Nat Rev Nephrol [Internet]. 2024; Available from: https://www.nature.com/articles/s41581-024-00806-4\u003c/li\u003e\n\u003cli\u003eKauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A. Antagonistic crosstalk between NF-\u0026kappa;B and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal [Internet]. 2013 [cited 2024 Mar 29];25:1939\u0026ndash;48. Available from: https://pubmed.ncbi.nlm.nih.gov/23770291/\u003c/li\u003e\n\u003cli\u003eWu QJ, Zhang TN, Chen HH, Yu XF, Lv J Le, Liu YY, et al. The sirtuin family in health and disease. Signal Transduction and Targeted Therapy 2022 7:1 [Internet]. 2022 [cited 2024 Mar 29];7:1\u0026ndash;74. Available from: https://www.nature.com/articles/s41392-022-01257-8\u003c/li\u003e\n\u003cli\u003eHe W, Wang Y, Zhang MZ, You L, Davis LS, Fan H, et al. Sirt1 activation protects the mouse renal medulla from oxidative injury. Journal of Clinical Investigation. 2010;120:1056\u0026ndash;68. \u003c/li\u003e\n\u003cli\u003eFunk JA, Schnellmann RG. Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1\u0026alpha; activation following ischemia-reperfusion injury. Toxicol Appl Pharmacol. 2013;273:345\u0026ndash;54. \u003c/li\u003e\n\u003cli\u003eFan H, Yang HC, You L, Wang YY, He WJ, Hao CM. The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury. Kidney Int [Internet]. 2013 [cited 2024 Mar 19];83:404\u0026ndash;13. Available from: https://pubmed.ncbi.nlm.nih.gov/23302720/\u003c/li\u003e\n\u003cli\u003e\u003c/li\u003e\n\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":"Sirtuin-1, CI-AKI, post-PCI, renalism","lastPublishedDoi":"10.21203/rs.3.rs-4686093/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4686093/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eContrast-induced acute kidney injury (CI-AKI) is a serious complication of clinical practice after cardiac catheterization. Sirtuin-1 is a crucial regulator of the protection of the kidney against ischemia/reperfusion injury, inflammation, and vasoconstriction. In the present study, we sought to investigate whether Sirtuin-1 may be an early diagnostic marker of CIN.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e76 patients admitted for elective percutaneous coronary interventions (PCI) for stable angina were enrolled between July 2022 and November 2022, and 50 patients were eligible to study. Sirtuin-1 values were measured by the Elisa kit before, 24 and 72 hours after the PCI.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThere is no statistically significant difference between CI-AKI (n\u0026thinsp;=\u0026thinsp;17) and non-AKI (n\u0026thinsp;=\u0026thinsp;33) groups regarding Sirtuin-1 between patient samples obtained before and after PCI.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThese findings refute the hypothesis that Sirtuin-1 may be clinically beneficial as a biomarker for CI-AKI following radiological procedures requiring intravascular administration of iodinated contrast media.\u003c/p\u003e","manuscriptTitle":"Sirtuin-1: A marker of contrast-induced nephropathy following percutaneous coronary intervention?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-10 12:27:52","doi":"10.21203/rs.3.rs-4686093/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":"b34ff6f6-90ef-429c-8e61-6af844814500","owner":[],"postedDate":"August 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-20T15:44:59+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-10 12:27:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4686093","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4686093","identity":"rs-4686093","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}