Advertisement

Association of statin use and the risk of end-stage renal disease: A nationwide Asian population-based case–control study

  • Shih-Yi Lin
    Affiliations
    Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taiwan

    Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan
    Search for articles by this author
  • Cheng-Li Lin
    Affiliations
    Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan

    College of Medicine, China Medical University, Taichung, Taiwan
    Search for articles by this author
  • Wu-Huei Hsu
    Affiliations
    Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taiwan

    Division of Pulmonary and Critical Care Medicine, China Medical University Hospital and China Medical University, Taichung, , Taiwan
    Search for articles by this author
  • Cheng-Chieh Lin
    Affiliations
    Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taiwan

    Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
    Search for articles by this author
  • Chiz-Tzung Chang
    Affiliations
    Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taiwan

    Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan
    Search for articles by this author
  • Chia-Hung Kao
    Correspondence
    Corresponding author at: Graduate Institute of Clinical Medicine Science, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 40447, Taiwan. Tel.: +886 4 22052121x7412; fax: +886 4 22336174.
    Affiliations
    Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taiwan

    Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
    Search for articles by this author
Published:February 24, 2016DOI:https://doi.org/10.1016/j.ejim.2016.02.012

      Highlights

      • The renal effects of statins remain unclear.
      • This population-based case–control study showed that statin use might be associated with increased ESRD risks.

      Abstract

      Background

      Although experimental models have shown that statins could alleviate glomerular damage and decrease urinary protein excretion, the renal effects of statins remain unclear. A case–control study was conducted using data from Taiwan's National Health Insurance system.

      Methods

      An end-stage renal disease (ESRD) group comprising 11,486 patients was established. Each patient was frequency-matched by age, sex, and comorbidities with one person without ESRD from the general population. Logistic regression analysis was performed to estimate the influence of statin use on ESRD risk.

      Results

      The overall adjusted odds ratios (ORs) of ESRD among patients who received statins was 1.59 (95% confidence interval = 1.50–1.68). The raised ESRD risk of statin remained consolidated regardless of statin type (P < .001), except lovastatin. Further, while stratified by cumulative define daily dose, the risk of ESRD increased with accumulative dosage of statins (P for trend < .001).

      Conclusion

      This population-based case–control study showed that statin use might be associated with increased ESRD risks. Large-scale randomized clinical trial encompassing statins of different kinds and populations of different comorbidities would be helpful to clarify the potential ESRD risks of statin users

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Mills E.J.
        • Rachlis B.
        • Wu P.
        • Devereaux P.J.
        • Arora P.
        • Perri D.
        Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients.
        J Am Coll Cardiol. 2008; 52: 1769-1781
        • Li C.
        • Lim S.W.
        • Choi B.S.
        • et al.
        Inhibitory effect of pravastatin on transforming growth factor beta1-inducible gene h3 expression in a rat model of chronic cyclosporine nephropathy.
        Am J Nephrol. Nov-Dec 2005; 25: 611-620
        • Christensen M.
        • Su A.W.
        • Snyder R.W.
        • Greco A.
        • Lipschutz J.H.
        • Madaio M.P.
        Simvastatin protection against acute immune-mediated glomerulonephritis in mice.
        Kidney Int. Feb 2006; 69: 457-463
        • Rabelink A.J.
        • Hene R.J.
        • Erkelens D.W.
        • Joles J.A.
        • Koomans H.A.
        Partial remission of nephrotic syndrome in patient on long-term simvastatin.
        Lancet. Apr 28 1990; 335: 1045-1046
        • Tonolo G.
        • Ciccarese M.
        • Brizzi P.
        • et al.
        Reduction of albumin excretion rate in normotensive microalbuminuric type 2 diabetic patients during long-term simvastatin treatment.
        Diabetes Care. 1997; 20: 1891-1895
        • Nielsen S.
        • Schmitz O.
        • Møller N.
        • et al.
        Renal function and insulin sensitivity during simvastatin treatment in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria.
        Diabetologia. 1993; 36: 1079-1086
        • Atthobari J.
        • Brantsma A.H.
        • Gansevoort R.T.
        • et al.
        The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study.
        Nephrol Dial Transplant. 2006; 21: 3106-3114
        • Rayner B.
        • Byrne M.
        • van Zyl S.R.
        A prospective clinical trial comparing the treatment of idiopathic membranous nephropathy and nephrotic syndrome with simvastatin and diet, versus diet alone.
        Clin Nephrol. 1996; 46: 219-224
        • Bianchi S.
        • Bigazzi R.
        • Caiazza A.
        • Campese V.M.
        A controlled, prospective study of the effects of atorvastatin on proteinuria and progression of kidney disease.
        Am J Kidney Dis. 2003; 41: 565-570
      1. Am J Kidney Dis. Feb 2002; 39: S1-266
        • Strippoli G.F.
        • Navaneethan S.D.
        • Johnson D.W.
        • et al.
        Effects of statins in patients with chronic kidney disease: meta-analysis and meta-regression of randomised controlled trials.
        BMJ. 2008; 336: 645-651
        • Sandhu S.
        • Wiebe N.
        • Fried L.F.
        • Tonelli M.
        Statins for improving renal outcomes: a meta-analysis.
        J Am Soc Nephrol. 2006; : 17(7)
        • Palmer S.C.
        • Craig J.C.
        • Navaneethan S.D.
        • Tonelli M.
        • Pellegrini F.
        • Strippoli G.F.
        Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis.
        Ann Intern Med. 2012; 157: 263-275
        • Athyros V.
        • Mikhailidis D.
        • Papageorgiou A.
        • et al.
        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: 728-734
        • Okma K.G.
        Cheng T-m, chinitz D, et al. six countries, six Health reform models? Health Care reform in Chile, Israel, Singapore, Switzerland, Taiwan and The Netherlands.
        J Comp Policy Anal. 2010; 12: 75-113
        • Lin S.Y.
        • Lin C.L.
        • Tseng C.H.
        • et al.
        Association between chronic osteomyelitis and risk of end-stage renal disease: a nationwide population-based cohort study.
        Medicine (Baltimore). 2015; 94e1141
        • Lin S.Y.
        • Lin C.L.
        • Liu J.H.
        • Yang Y.F.
        • Huang C.C.
        • Kao C.H.
        Association between helicobacter pylori infection and the subsequent risk of end-stage renal disease: a nationwide population-based cohort study.
        Int J Clin Pract. 2015; 69: 604-610
        • Lin S.Y.
        • Lin W.M.
        • Lin C.L.
        • Yang T.Y.
        • Sung F.C.
        • Wang Y.H.
        • et al.
        The relationship between secondary hyperparathyroidism and thyroid cancer in end stage renal disease: a population based cohort study.
        Eur J Intern Med. 2014; 25: 276-280
        • Chen H.Y.
        • Hsu S.Y.
        • Chang Y.C.
        • Lin C.C.
        • Sung F.C.
        • Chen W.C.
        • et al.
        Association between statin use and open-angle glaucoma in hyperlipidemia patients: a Taiwanese population-based case–control study.
        Medicine (Baltimore). 2015; 94e2018
        • Feng A.
        • Chuang E.
        • Wu S.H.
        • Wang J.C.
        • Chang S.N.
        • Lin C.L.
        • et al.
        The effect of statins on the occurrence of peptic ulcer.
        Eur J Intern Med. 2015; 26: 731-735
        • Chuang C.S.
        • Yang T.Y.
        • Muo C.H.
        • Su H.L.
        • Sung F.C.
        • Kao C.H.
        Hyperlipidemia, statin use and the risk of developing depression: a nationwide retrospective cohort study.
        Gen Hosp Psychiatry. 2014; 36: 497-501
        • Baigent C.
        • Landray M.J.
        • Reith C.
        • et al.
        The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.
        Lancet. Jun 25 2011; 377: 2181-2192
        • Stone N.J.
        • Merz C.N.B.
        • ScM F.
        • et al.
        ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults.
        J Am Coll Cardiol. 2013; 2013
        • Manttari M.
        • Tiula E.
        • Alikoski T.
        • Manninen V.
        Effects of hypertension and dyslipidemia on the decline in renal function.
        Hypertension. Oct 1995; 26: 670-675
        • de Boer I.H.
        • Astor B.C.
        • Kramer H.
        • et al.
        Lipoprotein abnormalities associated with mild impairment of kidney function in the multi-ethnic study of Atherosclerosis.
        Clin J Am Soc Nephrol. January 1 2008; 3 (2008): 125-132
        • Bussolati B.
        • Deregibus M.C.
        • Fonsato V.
        • et al.
        Statins prevent oxidized LDL-induced injury of glomerular podocytes by activating the phosphatidylinositol 3-kinase/AKT-signaling pathway.
        J Am Soc Nephrol. Jul 2005; 16: 1936-1947
        • Yoshimura A.
        • Nemoto T.
        • Sugenoya Y.
        • et al.
        Effect of simvastatin on proliferative nephritis and cell-cycle protein expression.
        Kidney Int Suppl. Jul 1999; 71: S84-S87
        • Mauro Vieira J.
        • Mantovani E.
        • Tavares Rodrigues L.
        • et al.
        Simvastatin attenuates renal inflammation, tubular transdifferentiation and interstitial fibrosis in rats with unilateral ureteral obstruction.
        Nephrol Dial Transplant. August 1 2005; 20 (2005): 1582-1591
        • Liao J.K.
        Effects of statins on 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition beyond low-density lipoprotein cholesterol.
        Am J Cardiol. Sep 5 2005; 96: 24F-33F
        • Rahman M.
        • Baimbridge C.
        • Davis B.R.
        • et al.
        Progression of kidney disease in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin versus usual care: a report from the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT).
        Am J Kidney Dis. Sep 2008; 52: 412-424
        • Tonelli M.
        • Moye L.
        • Sacks F.M.
        • Cole T.
        • Curhan G.C.
        Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease.
        J Am Soc Nephrol. Jun 2003; 14: 1605-1613
        • Fried L.F.
        Effects of HMG-CoA reductase inhibitors (statins) on progression of kidney disease.
        Kidney Int. Sep 2008; 74: 571-576
        • Sandhu S.
        • Wiebe N.
        • Fried L.F.
        • Tonelli M.
        Statins for improving renal outcomes: a meta-analysis.
        J Am Soc Nephrol. Jul 2006; 17: 2006-2016
      2. YL Yan, B Qiu, J Wang, SB Deng, L Wang, XD Jing, JL Du, YJ Liu, Q She. High-intensity statin therapy in patients with chronic kidney disease: a systematic review and meta-analysis. BMJ open. 205;5

        • Ekinci E.I.
        • Jerums G.
        • Skene A.
        • et al.
        Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function.
        Diabetes Care. 2013; 36: 3620-3626
        • Palatini P.
        Glomerular hyperfiltration: a marker of early renal damage in pre-diabetes and pre-hypertension.
        Nephrol Dial Transplant. 2012; 27: 1708-1714
        • Lai C.L.
        • Chou H.W.
        • Arnole Chen
        • Lai M.S.
        Effects on atorvastatin and rosuvastatin on renal function in patients with type 2 diabetes mellitus.
        Am J Cardiol. 2015; 115: 619-624
        • Banglore S.
        • Rana F.
        • Kees H.
        • Rachel L.
        • Liffert V.
        • Demico David A.
        • et al.
        Waters, treating to new targets steering committee and investigators.
        Am J Cardiol. 2014; 113: 2018-2020
        • Wagstaff L.R.
        • Mitton M.W.
        • Arvik B.M.
        • Doraiswamy P.M.
        Statin-associated memory loss: analysis of 60 case reports and review of the literature.
        Pharmacotherapy. Jul 2003; 23: 871-880
        • Golomb B.A.
        • Evans M.A.
        Statin adverse effects.
        Am J Cardiovasc Drugs. 2008; 8: 373-418
        • de Denus S.
        • Spinler S.A.
        • Miller K.
        • Peterson A.M.
        Statins and liver toxicity: a meta-analysis.
        Pharmacotherapy. May 2004; 24: 584-591
        • Ridker P.M.
        • Danielson E.
        • Fonseca F.A.
        • et al.
        Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
        N Engl J Med. Nov 20 2008; 359: 2195-2207
        • Corona G.
        • Boddi V.
        • Balercia G.
        • et al.
        The effect of statin therapy on testosterone levels in subjects consulting for erectile dysfunction.
        J Sex Med. Apr 2010; 7: 1547-1556
        • Dormuth C.R.
        • Hemmelgarn B.R.
        • Paterson J.M.
        • et al.
        Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases.
        BMJ. 2013; 346: f880