Effects of Atorvastatin and Rosuvastatin on Renal Function in Patients With Type 2 Diabetes Mellitus
2014; Elsevier BV; Volume: 115; Issue: 5 Linguagem: Inglês
10.1016/j.amjcard.2014.12.009
ISSN1879-1913
AutoresChao‐Lun Lai, Hsu‐Wen Chou, K. Arnold Chan, Mei‐Shu Lai,
Tópico(s)Health Systems, Economic Evaluations, Quality of Life
ResumoWe performed this population-based study to investigate the effects of atorvastatin and rosuvastatin on renal function in patients with type 2 diabetes. From the Taiwan National Health Insurance Pay-for-Performance program for diabetes mellitus database, 2006 to 2009, type 2 diabetic patients aged 40 to 100 years with the first prescription of atorvastatin or rosuvastatin were identified. All the data were linked to the National Health Insurance claims database, 2000 to 2010, to construct longitudinal health care data. The Modification of Diet in Renal Disease equation was used to calculate the estimated glomerular filtration rate (eGFR), and the eGFRs between baseline and the end of follow-up (maximum 2 years) were compared. Totally, 3,601 new users of atorvastatin and 1,968 new users of rosuvastatin were included. The median follow-up was 238 days in atorvastatin users and 210 days in rosuvastatin users. The eGFR at baseline was 72.3 ± 25.9 ml/min/1.73 m2 in atorvastatin users and 73.7 ± 27.3 ml/min/1.73 m2 in rosuvastatin users. In both statin groups, we found no significant change in eGFR (+0.1 ml/min/1.73 m2, 95% confidence interval −0.4 to 0.7, p = 0.62 in atorvastatin users; −0.1 ml/min/1.73 m2, 95% confidence interval −0.8 to 0.6, p = 0.77 in rosuvastatin users). In conclusion, neither treatment with atorvastatin nor rosuvastatin was associated with a significant change of renal function in type 2 diabetic patients. We performed this population-based study to investigate the effects of atorvastatin and rosuvastatin on renal function in patients with type 2 diabetes. From the Taiwan National Health Insurance Pay-for-Performance program for diabetes mellitus database, 2006 to 2009, type 2 diabetic patients aged 40 to 100 years with the first prescription of atorvastatin or rosuvastatin were identified. All the data were linked to the National Health Insurance claims database, 2000 to 2010, to construct longitudinal health care data. The Modification of Diet in Renal Disease equation was used to calculate the estimated glomerular filtration rate (eGFR), and the eGFRs between baseline and the end of follow-up (maximum 2 years) were compared. Totally, 3,601 new users of atorvastatin and 1,968 new users of rosuvastatin were included. The median follow-up was 238 days in atorvastatin users and 210 days in rosuvastatin users. The eGFR at baseline was 72.3 ± 25.9 ml/min/1.73 m2 in atorvastatin users and 73.7 ± 27.3 ml/min/1.73 m2 in rosuvastatin users. In both statin groups, we found no significant change in eGFR (+0.1 ml/min/1.73 m2, 95% confidence interval −0.4 to 0.7, p = 0.62 in atorvastatin users; −0.1 ml/min/1.73 m2, 95% confidence interval −0.8 to 0.6, p = 0.77 in rosuvastatin users). In conclusion, neither treatment with atorvastatin nor rosuvastatin was associated with a significant change of renal function in type 2 diabetic patients. Several studies have refuted the adverse effect of statin therapy on renal function.1Fassett R.G. Robertson I.K. Ball M.J. Geraghty D.P. Coombes J.S. Effect of atorvastatin on kidney function in chronic kidney disease: a randomised double-blind placebo-controlled trial.Atherosclerosis. 2010; 213: 218-224Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar, 2Bangalore S. Fayyad R. Hovingh G.K. Laskey R. Vogt L. DeMicco D.A. Waters D.D. Treating to New Targets Steering Committee and InvestigatorsStatin and the risk of renal-related serious adverse events: analysis from the IDEAL, TNT, CARDS, ASPEN, SPARCL, and other placebo-controlled trials.Am J Cardiol. 2014; 113: 2018-2020Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 3Palmer S.C. Navaneethan S.D. Craig J. Johnson D.W. Perkovic V. Hegbrant J. Strippoli G.F. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis.Cochrane Database Syst Rev. 2014; 5: CD007784PubMed Google Scholar, 4Savarese G. Musella F. Volpe M. Paneni F. Perrone-Filardi P. Effects of atorvastatin and rosuvastatin on renal function: a meta-analysis.Int J Cardiol. 2013; 167: 2482-2489Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 5Takagi H. Umemoto T. A meta-analysis of randomized trials for effects of atorvastatin on renal function in chronic kidney disease.Int J Cardiol. 2011; 152: 242-244Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 6Wu Y. Wang Y. An C. Dong Z. Liu H. Zhang Y. Zhang M. An F. Effects of rosuvastatin and atorvastatin on renal function: meta-analysis.Circ J. 2012; 76: 1259-1266Crossref PubMed Scopus (29) Google Scholar, 7Athyros V.G. Mikhailidis D.P. Papageorgiou A.A. Symeonidis A.N. Pehlivanidis A.N. Bouloukos V.I. Elisaf M. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study.J Clin Pathol. 2004; 57: 728-734Crossref PubMed Scopus (391) Google Scholar, 8Collins R. Armitage J. Parish S. Sleigh P. Peto R. Heart Protection Study Collaborative GroupMRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial.Lancet. 2003; 361: 2005-2016Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 9Sandhu S. Wiebe N. Fried L.F. Tonelli M. Statins for improving renal outcomes: a meta-analysis.J Am Soc Nephrol. 2006; 17: 2006-2016Crossref PubMed Scopus (427) Google Scholar However, a few large-scale observational studies reported an association between statins, especially high-potency statins, and acute kidney injury.10Corrao G. Soranna D. Casula M. Merlino L. Porcellini M.G. Catapano A.L. High-potency statins increase the risk of acute kidney injury: evidence from a large population-based study.Atherosclerosis. 2014; 234: 224-229Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 11Dormuth C.R. Hemmelgarn B.R. Paterson J.M. James M.T. Teare G.F. Raymond C.B. Lafrance J.P. Levy A. Garg A.X. Ernst P. Canadian Network for Observational Drug Effect Studies (CNODES)Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases.BMJ. 2013; 346: f880Crossref PubMed Scopus (183) Google Scholar, 12Chung Y.H. Lee Y.C. Chang C.H. Lin M.S. Lin J.W. Lai M.S. Statins of high versus low cholesterol-lowering efficacy and the development of severe renal failure.Pharmacoepidemiol Drug Saf. 2013; 22: 583-592Crossref PubMed Scopus (25) Google Scholar The aim of this study was to evaluate the effects of 2 high-potency statins, atorvastatin and rosuvastatin, on renal function in adult type 2 diabetic patients in an ethnic Chinese population. A retrospective cohort study using the longitudinal National Health Insurance (NHI) claims data of Taiwan was conducted.MethodsTaiwan launched a single-payer NHI Program since 1995. As of 2007, >98% of the total Taiwanese population is covered by the program. Patient identification numbers, gender, birthdays, dates of hospital admission and discharge, diagnoses, and drugs dispensed are available in the NHI claims database. The diagnoses are coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) system. Under the NHI system, most health care services are reimbursed on a fee-for-service basis. Since 2001, the NHI program has implemented a Pay-for-Performance (P4P) program for diabetes mellitus.13Lee T.T. Cheng S.H. Chen C.C. Lai M.S. A pay-for-performance program for diabetes care in Taiwan: a preliminary assessment.Am J Manag Care. 2010; 16: 65-69PubMed Google Scholar Hospitals and community clinics with qualified physicians can voluntarily apply to participate in the NHI P4P program. The participating physicians then can enroll patients in the NHI P4P program. The NHI P4P program reimburses participating clinicians with additional physician fees and case management fees in addition to regular reimbursement for health care services to increase comprehensive follow-up visits including annual diabetes-specific examinations, such as laboratory tests. Clinical characteristics of the enrolled patients, including habits of smoking and alcohol drinking, body height, body weight, body mass index, and key follow-up laboratory data concerning diabetic care, were reported by the hospitals themselves periodically and were entered into the P4P-specific database automatically.13Lee T.T. Cheng S.H. Chen C.C. Lai M.S. A pay-for-performance program for diabetes care in Taiwan: a preliminary assessment.Am J Manag Care. 2010; 16: 65-69PubMed Google ScholarOur data came from 2 databases. One database contained information collected from the NHI P4P program for the period from January 2006 to December 2010 and was used to obtain major clinical characteristics of patients and physicians. The patients' NHI P4P records were then linked to the NHI claims database through 2000 to 2010 by patient identification number to identify co-morbidities, drug exposures, and medical utilizations during the baseline period. To comply with privacy regulations, personal identifiers were encrypted, and all data were analyzed anonymously. The study protocol was approved by the Institutional Review Board of the National Taiwan University Hospital.All type 2 diabetic patients aged between 40 and 100 years with the first prescription of atorvastatin or rosuvastatin were identified from the NHI P4P database through 2006 to 2009, and their longitudinal claims data were extracted from the NHI claims database. The date on which the first statin was prescribed was operationally set as the index date. Background characteristics and co-morbidities of the enrolled subjects were assessed within the baseline 6-month period before the index date. Patients who had received any type of statin or any type of renal replacement therapy during the baseline 6-month period were excluded. Besides, we also excluded subjects receiving >1 statin at the index date, subjects without baseline serum creatinine level, and subjects with abnormally high baseline serum alanine aminotransferase levels (>1,000 IU/L). Only subjects with at least 1 report of serum creatinine level during the follow-up period were retained in the study cohort.All subjects were followed from their index dates until they had a prescription of another type of statin, no refill for statins after 1.5 times the duration of their last prescription of statins, died, withdrawal from health insurance coverage, initiation of any renal replacement therapy, maximum 2 years of follow-up, or reached the end of the study at December 31, 2010, whichever came first.The abbreviated Modification of Diet in Renal Disease equation14Levey A.S. Coresh J. Balk E. Kausz A.T. Levin A. Steffes M.W. Hogg R.J. Perrone R.D. Lau J. Eknoyan G. National Kidney FoundationNational Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Ann Intern Med. 2003; 139: 137-147Crossref PubMed Scopus (3626) Google Scholar was used to calculate the estimated glomerular filtration rate (eGFR). The baseline eGFR was calculated based on the last record of serum creatinine level before the index date, and the follow-up eGFR was calculated based on the last record of serum creatinine level before the end of follow-up (last observation carried forward approach). The change of eGFR between end of follow-up and baseline was calculated for each subject accordingly.In addition to baseline age at prescription of specific study drugs and gender, we assessed the potential confounders such as smoking, alcohol drinking, body mass index, key laboratory data at baseline, co-morbidities, history of exposure to nephrotoxic drugs, specialty of prescribing physicians, and medical utilizations within the baseline 6-month period. The laboratory data (also using last observation carried forward approach) included fasting blood glucose, glycated hemoglobin (HbA1c), alanine aminotransferase, uric acid, low-density lipoprotein cholesterol, and baseline eGFR. The stage of chronic kidney disease (CKD) was defined according to baseline eGFR.15National Kidney FoundationK/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Am J Kidney Dis. 2002; 39: S46-75Abstract Full Text Full Text PDF Google Scholar Most of the co-morbidities were extracted based on the revised ICD-9-CM coding algorithms for Elixhauser Index16Quan H. Sundararajan V. Halfon P. Fong A. Burnand B. Luthi J.C. Saunders L.D. Beck C.A. Feasby T.E. Ghali W.A. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.Med Care. 2005; 43: 1130-1139Crossref PubMed Scopus (6337) Google Scholar except for myocardial infarction (410.x and 412.x) and cerebrovascular disease (362.34 and 430.x to 438.x). Only those co-morbidities with a prevalence of >1% were retained in the analysis (Table 1). The list of potential nephrotoxic drugs were acetaminophen, aspirin, nonsteroidal anti-inflammatory drugs, allopurinol, penicillins, cephalosporins, sulfonamides, aminoglycosides, quinolones, thiazide diuretics, loop diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), H2-receptor antagonists, and proton pump inhibitors.17Naughton C.A. Drug-induced nephrotoxicity.Am Fam Physician. 2008; 78: 743-750PubMed Google Scholar, 18Pannu N. Nadim M.K. An overview of drug-induced acute kidney injury.Crit Care Med. 2008; 36: S216-223Crossref PubMed Scopus (237) Google Scholar The specialty of prescribing physicians included family medicine, internal medicine, cardiology, nephrology, and endocrinology. Medical utilizations were defined as number of outpatient visits and number of hospitalizations during baseline 6-month period.Table 1Baseline characteristics of enrolled subjectsVariableAtorvastatinRosuvastatinP value(n=3601)(n=1968)Age (years)62.8 ± 10.561.7 ± 10.2<0.0001Men1683 (47%)980 (50%)0.029Smoker1672 (46%)835 (42%)0.004Alcohol use1679 (47%)813 (41%)<0.001Body mass index (kg/m2)26.4 ± 3.726.5 ± 3.90.27Baseline Fasting glucose (mg/dL)151.8 ± 50.0155.1 ± 57.40.037 Glycated hemoglobin (%)7.9 ± 1.68.0 ± 1.70.019 Alanine aminotransferase (IU/L)29.1 ± 22.528.2 ± 19.60.25 Uric acid (md/dL)6.3 ± 1.86.2 ± 1.60.36 LDL-C (mg/dL)136.4 ± 32.2139.7 ± 34.5<0.001 Creatinine (mg/dL)1.1 ± 0.51.1 ± 1.10.31 eGFR (mL/min/1.73m2)72.3 ± 25.973.7 ± 27.30.06Chronic kidney disease stage0.37 1856 (24%)476 (24%) 21608 (45%)876 (45%) 3964 (27%)541 (27%) 4152 (4%)62 (3%) 521 (1%)13 (1%)Comorbidities Myocardial infarction22 (1%)14 (1%)0.65 Cerebrovascular disease236 (7%)128 (7%)0.94 Congestive heart failure145 (4%)40 (2%)<0.0001 Cardiac arrhythmia117 (3%)74 (4%)0.32 Valvular heart disease51 (1%)23 (1%)0.44 Peripheral vascular disorder83 (2%)41 (2%)0.59 Hypertension1981 (55%)1046 (53%)0.18 Paralysis25 (1%)5 (0%)0.035 Other neurological disorder42 (1%)18 (1%)0.38 Chronic pulmonary disease277 (8%)111 (6%)0.004 Hypothyroidism38 (1%)31 (2%)0.09 Liver disease296 (8%)173 (9%)0.46 Peptic ulcer disease, excluding bleeding265 (7%)125 (6%)0.16 Cancer131 (4%)60 (3%)0.25 Collagen vascular disease109 (3%)38 (2%)0.015 Psychosis26 (1%)21 (1%)0.18 Depression116 (3%)44 (2%)0.035Exposure to nephrotoxic drugs Acetaminophen1559 (43%)804 (41%)0.08 Aspirin131 (4%)44 (2%)0.004 NSAIDs1693 (47%)936 (48%)0.70 Allopurinol104 (3%)48 (2%)0.33 Penicillins561 (16%)294 (15%)0.53 Cephalosporins648 (18%)355 (18%)0.97 Sulfonamides281 (8%)159 (8%)0.72 Aminoglycosides121 (3%)65 (3%)0.91 Quinolones117 (3%)67 (3%)0.76 Thiazide diuretics206 (6%)107 (5%)0.66 Loop diuretics281 (8%)159 (8%)0.72 ACEIs666 (18%)316 (16%)0.023 Angiotensin receptor blockers1207 (34%)639 (32%)0.43 H2-receptor antagonists501 (14%)253 (13%)0.27 Proton pump inhibitors136 (4%)87 (4%)0.24Specialty of prescribing physicians<0.0001 Family medicine456 (13%)71 (4%) Internal medicine580 (16%)290 (15%) Cardiology223 (6%)124 (6%) Nephrology79 (2%)52 (3%) Endocrinology1930 (54%)1391 (71%)Medical utilizations Outpatient visits14.9 ± 11.914.4 ± 11.50.16 Hospitalizations0.1 ± 0.40.1 ± 0.40.55Values are expressed as mean ± standard deviation or number (percentage).ACEI = angiotensin-converting-enzyme inhibitor; eGFR = estimated glomerular filtration rate; LDL-C = low-density lipoprotein cholesterol; NSAID = non-steroidal anti-inflammatory drug. Open table in a new tab Categorical data are presented in contingency tables, and continuous variables are presented as mean ± SD. The chi-square test and 2-sample t test were used to test differences between atorvastatin users and rosuvastatin users. The eGFRs between end of follow-up and baseline period within each statin group were compared by paired t test. Multiple linear regression model was applied to compare the change of eGFR between 2 statin groups. Baseline eGFR and all the potential confounders listed in Table 1 except serum creatinine level were included as regressors. The primary analysis was repeated for different subgroups such as genders, age groups, HbA1c levels, CKD stages, and exposure to ACEIs/ARBs or not. We also performed a stratified analysis according to the maximum daily dosages of statins as patients ever receiving atorvastatin 80 mg/day or rosuvastatin 40 mg/day in any prescription during the follow-up period were classified as high-dose users and others were classified as low-dose users.All analyses were performed with SAS software, version 9.2 (SAS Institute, Inc., Cary, North Carolina). All p values reported are 2 sided, and the significant level was set at <0.05.ResultsTotally, 3,601 incident users of atorvastatin and 1,968 incident users of rosuvastatin were included in this study (Figure 1). Compared with rosuvastatin users, atorvastatin users were older and were more likely to be women, have habits of cigarette smoking and alcohol consumption, and have lower levels of fasting glucose, HbA1c, and low-density lipoprotein cholesterol. Atorvastatin users were more likely to have congestive heart failure, paralysis, chronic pulmonary disease, collagen vascular disease, depression, exposure to aspirin, and ACEIs within baseline 6-month period than rosuvastatin users. Atorvastatin was more likely to be prescribed by family physicians, whereas rosuvastatin was more likely to be prescribed by endocrinologists (Table 1).At baseline, the mean eGFR was 72.3 ± 25.9 ml/min/1.73 m2 in atorvastatin users and 73.7 ± 27.3 ml/min/1.73 m2 in rosuvastatin users. The mean daily dosage was 13.3 ± 10.4 mg for atorvastatin and 8.9 ± 4.7 mg for rosuvastatin. After a median follow-up of 238 days in atorvastatin users (interquartile range [IQR] 124 to 461 days) and 210 days in rosuvastatin users (IQR 116 to 402 days), we observed no change in eGFR within either statin group (change of eGFR +0.1 ml/min/1.73 m2, 95% confidence interval [CI] −0.4 to 0.7 ml/min/1.73 m2 in atorvastatin users; and −0.1 ml/min/1.73 m2, 95% CI −0.8 to 0.6 ml/min/1.73 m2 in rosuvastatin users). After accounting for baseline differences, no significant difference existed in the change of eGFR between atorvastatin users and rosuvastatin users (adjusted p = 0.27; Table 2 and Figure 2).Table 2Comparison of estimated glomerular filtration rate between study groupseGFR (mL/min/1.73m2)AtorvastatinRosuvastatinCrude p∗Comparison between atorvastatin group and rosuvastatin group by 2-sample t test.Adjusted p†Comparison between atorvastatin group and rosuvastatin group by multiple linear regression model with adjustment for potential confounders.mean (95% CI)mean (95% CI)Baseline72.3 (71.4 - 73.1)73.7 (72.5 - 74.9)0.06End of follow-up72.4 (71.5 - 73.3)73.6 (72.4 - 74.8)0.13Change0.1 (-0.4 - 0.7)-0.1 (-0.8 - 0.6)0.27Crude p‡Comparison between end of follow-up and baseline by paired t test.0.620.77CI = confidence interval; eGFR = estimated glomerular filtration rate.∗ Comparison between atorvastatin group and rosuvastatin group by 2-sample t test.† Comparison between atorvastatin group and rosuvastatin group by multiple linear regression model with adjustment for potential confounders.‡ Comparison between end of follow-up and baseline by paired t test. Open table in a new tab Figure 2Mean with 95% confidence interval of the change of eGFR in atorvastatin and rosuvastatin groups. eGFR = estimated glomerular filtration rate (mL/min/1.73 m2).View Large Image Figure ViewerDownload Hi-res image Download (PPT)The lack of difference in change of eGFR between atorvastatin users and rosuvastatin users was consistent in most of the prespecified subgroups (Figure 3), including patients with different genders, different age groups, different levels of HbA1c at baseline, ever/never exposure to ACEIs/ARBs at baseline, high-dose users (mean daily dosage 52.2 ± 26.3 mg in atorvastatin users and 22.2 ± 13.3 mg in rosuvastatin users), and low-dose users (mean daily dosage 13.1 ± 9.7 mg in atorvastatin users and 8.8 ± 4.5 mg in rosuvastatin users). Both atorvastatin users and rosuvastatin users showed a similar phenomenon of deterioration in eGFR in patients with underlying CKD in stage 1 to 2 and improvement in eGFR in patients with underlying CKD in stages 3 and 4 to 5.Figure 3Effects of atorvastatin and rosuvastatin on change of estimated glomerular filtration rate in subgroups. ACEI = angiotensin-converting-enzyme inhibitor; ARB = angiotensin receptor blocker; CI = confidence interval; CKD = chronic kidney disease; ΔeGFR = change of estimated glomerular filtration rate; HbA1c = glycated hemoglobin. *Comparison between atorvastatin group and rosuvastatin group by multiple linear regression model with adjustment for potential confounders.View Large Image Figure ViewerDownload Hi-res image Download (PPT)DiscussionIn this ethnic Chinese type 2 diabetic population, the effects of 2 high-potency statins, atorvastatin and rosuvastatin, on renal function were investigated using insurance claims database including key laboratory tests related to diabetic care. We found that both atorvastatin and rosuvastatin were not associated with a significant change of eGFR. Although there was deterioration in eGFR in patients with underlying CKD in stage 1 to 2, significant improvement in eGFR in patients with underlying CKD in stage 3 and stage 4 to 5 were noted in both high-potency statin groups.Much evidence concerning renal effect of statins comes from clinical trials. Both the Heart Protection Study8Collins R. Armitage J. Parish S. Sleigh P. Peto R. Heart Protection Study Collaborative GroupMRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial.Lancet. 2003; 361: 2005-2016Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar and the Greek Atorvastatin and Coronary Heart Disease Evaluation study7Athyros V.G. Mikhailidis D.P. Papageorgiou A.A. Symeonidis A.N. Pehlivanidis A.N. Bouloukos V.I. Elisaf M. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study.J Clin Pathol. 2004; 57: 728-734Crossref PubMed Scopus (391) Google Scholar found improvement in creatinine clearance after statin treatment. Several meta-analysis with pooling of results from clinical trials also found renal protective effect in high-potency statins including atorvastatin and rosuvastatin.2Bangalore S. Fayyad R. Hovingh G.K. Laskey R. Vogt L. DeMicco D.A. Waters D.D. Treating to New Targets Steering Committee and InvestigatorsStatin and the risk of renal-related serious adverse events: analysis from the IDEAL, TNT, CARDS, ASPEN, SPARCL, and other placebo-controlled trials.Am J Cardiol. 2014; 113: 2018-2020Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 4Savarese G. Musella F. Volpe M. Paneni F. Perrone-Filardi P. Effects of atorvastatin and rosuvastatin on renal function: a meta-analysis.Int J Cardiol. 2013; 167: 2482-2489Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 5Takagi H. Umemoto T. A meta-analysis of randomized trials for effects of atorvastatin on renal function in chronic kidney disease.Int J Cardiol. 2011; 152: 242-244Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 6Wu Y. Wang Y. An C. Dong Z. Liu H. Zhang Y. Zhang M. An F. Effects of rosuvastatin and atorvastatin on renal function: meta-analysis.Circ J. 2012; 76: 1259-1266Crossref PubMed Scopus (29) Google Scholar, 9Sandhu S. Wiebe N. Fried L.F. Tonelli M. Statins for improving renal outcomes: a meta-analysis.J Am Soc Nephrol. 2006; 17: 2006-2016Crossref PubMed Scopus (427) Google Scholar Although our study did not show a significant improvement in renal function in both atorvastatin and rosuvastatin groups, our findings were in line with the results from clinical trials that atorvastatin and rosuvastatin did not influence renal function adversely.In contrast to clinical trials, several large-scale observational studies,10Corrao G. Soranna D. Casula M. Merlino L. Porcellini M.G. Catapano A.L. High-potency statins increase the risk of acute kidney injury: evidence from a large population-based study.Atherosclerosis. 2014; 234: 224-229Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 11Dormuth C.R. Hemmelgarn B.R. Paterson J.M. James M.T. Teare G.F. Raymond C.B. Lafrance J.P. Levy A. Garg A.X. Ernst P. Canadian Network for Observational Drug Effect Studies (CNODES)Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases.BMJ. 2013; 346: f880Crossref PubMed Scopus (183) Google Scholar including 1 study from our colleagues,12Chung Y.H. Lee Y.C. Chang C.H. Lin M.S. Lin J.W. Lai M.S. Statins of high versus low cholesterol-lowering efficacy and the development of severe renal failure.Pharmacoepidemiol Drug Saf. 2013; 22: 583-592Crossref PubMed Scopus (25) Google Scholar using administrative data reported association between acute kidney injury and treatment with statins, especially high-potency ones. Although these studies possessed huge case number, they relied on only diagnoses in claims database without details of laboratory tests. Our study used a specific claims database with results of key laboratory tests including serum creatinine level for calculation of eGFR for each subject. The different conclusions between our study and previous observational studies10Corrao G. Soranna D. Casula M. Merlino L. Porcellini M.G. Catapano A.L. High-potency statins increase the risk of acute kidney injury: evidence from a large population-based study.Atherosclerosis. 2014; 234: 224-229Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 11Dormuth C.R. Hemmelgarn B.R. Paterson J.M. James M.T. Teare G.F. Raymond C.B. Lafrance J.P. Levy A. Garg A.X. Ernst P. Canadian Network for Observational Drug Effect Studies (CNODES)Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases.BMJ. 2013; 346: f880Crossref PubMed Scopus (183) Google Scholar, 12Chung Y.H. Lee Y.C. Chang C.H. Lin M.S. Lin J.W. Lai M.S. Statins of high versus low cholesterol-lowering efficacy and the development of severe renal failure.Pharmacoepidemiol Drug Saf. 2013; 22: 583-592Crossref PubMed Scopus (25) Google Scholar underscore the limitation of observational studies depending on only diagnoses in administrative databases.The influence of statins on renal function in patients with CKD is of interest. In our study, both atorvastatin and rosuvastatin were associated with a decrease of eGFR in patients with CKD stage 1 to 2. Conversely, a significant improvement in eGFR was found in patients with CKD stage 3 and stage 4 to 5 in both statin groups. Nevertheless, 2 Cochrane reviews stated that statins did not affect the decrease in renal function in patients with CKD.3Palmer S.C. Navaneethan S.D. Craig J. Johnson D.W. Perkovic V. Hegbrant J. Strippoli G.F. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis.Cochrane Database Syst Rev. 2014; 5: CD007784PubMed Google Scholar, 19Navaneethan S.D. Pansini F. Perkovic V. Manno C. Pellegrini F. Johnson D.W. Craig J.C. Strippoli G.F. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis.Cochrane Database Syst Rev. 2009; 2: CD007784PubMed Google Scholar Whether our findings reveal a different impact of statin therapy in patients with different stages of CKD or nothing but the phenomenon of “statistic regression towards the mean”20Bland J.M. Altman D.G. Regression towards the mean.BMJ. 1994; 308: 1499Crossref PubMed Scopus (417) Google Scholar, 21Bland J.M. Altman D.G. Some examples of regression towards the mean.BMJ. 1994; 309: 780Crossref PubMed Scopus (304) Google Scholar deserves further investigation.Some limitations of our study have to be acknowledged. Firstly, most clinical trials involving statin therapy have long follow-up durations of up to 4 to 5 years.7Athyros V.G. Mikhailidis D.P. Papageorgiou A.A. Symeonidis A.N. Pehlivanidis A.N. Bouloukos V.I. Elisaf M. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek At
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