Long-term effects of various types of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on changes in glomerular filtration rate in Korea

Abstract

Few long-term follow-up studies have compared the changes in renal function according to the type of statin used in Korea. We compared the long-term effects of statin intensity and type on the changes in the glomerular filtration rate (GFR). We extracted data of patients who took statin for the first time. We analyzed whether or not different statins affect the changes in GFR at 3 months after baseline and 4 years after. We included 3678 patients and analyzed the changes in GFR. The GFR decreased by 3.2%±0.4% on average 4 years after the first statin prescription, indicating statistically significant deterioration (from 83.5±0.4 mL/min/1.73 m² to 79.9±0.4 mL/min/1.73 m², P<0.001). When comparing the GFR among different statins, significant differences were observed between atorvastatin and fluvastatin (−5.3%±0.7% vs. 1.2%±2.2%, P<0.05) and between atorvastatin and simvastatin (−5.3%±0.7% vs. −0.7%±0.8%, P<0.05). In pitavastatin (odds ratio [OR]=0.64, 95% confidence interval [CI]=0.46–0.87, P<0.005) and simvastatin (OR=0.69, 95% CI=0.53–0.91, P<0.008), the GFR rate that decreased by<60 mL/min/1.73 m² was significantly lower than that of atorvastatin. Regarding long-term statin intake, GFR changed with the type of statin. This work is the first in Korea to compare each statin in terms of changes in the GFR after the statin prescription.

Keywords

statin / glomerular filtration rate / HMG-CoA reductase inhibitor / chronic kidney disease

References

[1] Grundy SM. HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med 1988; 319(1): 24–33

[2] Lee MH, Kim HC, Ahn SV, Hur NW, Choi DP, Park CG, Suh I. Prevalence of dyslipidemia among Korean adults: Korea national health and nutrition survey 1998–2005. Diabetes Metab J 2012; 36(1): 43–55

[3] European Association for Cardiovascular Prevention & Rehabilitation, Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, Agewall S, Alegria E, Chapman MJ, Durrington P, Erdine S, Halcox J, Hobbs R, Kjekshus J, Filardi PP, Riccardi G, Storey RF, Wood D; ESC Committee for Practice Guidelines (CPG) 2008–2010 and 2010–2012 Committees. EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011; 32(14): 1769–1818

[4] Ahn JH, Yu JH, Ko SH, Kwon HS, Kim DJ, Kim JH, Kim CS, Song KH, Won JC, Lim S, Choi SH, Han K, Cha BY, Kim NH; Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association. Prevalence and determinants of diabetic nephropathy in Korea: Korea national health and nutrition examination survey. Diabetes Metab J 2014; 38(2): 109–119

[5] Kang YH, Jeong DW, Son SM. Prevalence of reduced kidney function by estimated glomerular filtration rate using an equation based on creatinine and cystatin C in metabolic syndrome and its components in Korean adults. Endocrinol Metab (Seoul) 2016; 31(3): 446–453

[6] Kidney Disease Outcomes Quality Initiative (K/DOQI) Group. K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis 2003; 41: I–IV, S1–91

[7] Agarwal R. Effects of statins on renal function. Am J Cardiol 2006; 97(5): 748–755

[8] Moon BS, Kim J, Kim JH, Hyun YY, Park SE, Oh HG, Park CY, Lee WY, Oh KW, Lee KB, Kim H, Park SW, Rhee EJ. Eligibility for statin treatment in Korean subjects with reduced renal function: an observational study. Endocrinol Metab (Seoul) 2016; 31(3): 402–409

[9] Athyros VG, Mikhailidis DP, Papageorgiou AA, Symeonidis AN, Pehlivanidis AN, Bouloukos VI, 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(7): 728–734

[10] Fried LF, Forrest KY, Ellis D, Chang Y, Silvers N, Orchard TJ. Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes. J Diabetes Complications 2001; 15(3): 113–119

[11] Tonelli M, Isles C, Craven T, Tonkin A, Pfeffer MA, Shepherd J, Sacks FM, Furberg C, Cobbe SM, Simes J, West M, Packard C, Curhan GC. Effect of pravastatin on rate of kidney function loss in people with or at risk for coronary disease. Circulation 2005; 112(2): 171–178

[12] Lee TM, Lin MS, Tsai CH, Chang NC. Add-on and withdrawal effect of pravastatin on proteinuria in hypertensive patients treated with AT receptor blockers. Kidney Int 2005; 68(2): 779–787

[13] Su X, Zhang L, Lv J, Wang J, Hou W, Xie X, Zhang H. Effect of statins on kidney disease outcomes: a systematic review and meta-analysis. Am J Kidney Dis 2016; 67(6): 881–892

[14] Kendrick J, Shlipak MG, Targher G, Cook T, Lindenfeld J, Chonchol M. Effect of lovastatin on primary prevention of cardiovascular events in mild CKD and kidney function loss: a post hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study. Am J Kidney Dis 2010; 55(1): 42–49

[15] Acharya T, Huang J, Tringali S, Frei CR, Mortensen EM, Mansi IA. Statin use and the risk of kidney disease with long-term follow-up (8.4-year study). Am J Cardiol 2016; 117(4): 647–655

[16] Garcia MM, Varela CG, Silva PF, Lima PR, Góes PM, Rodrigues MG, Silva MdeL, Ladeia AM, Guimarães AC, Correia LC. Endothelial effect of statin therapy at a high dose versus low dose associated with ezetimibe. Arq Bras Cardiol 2016; 106(4): 279–288

[17] Clarke AT, Johnson PC, Hall GC, Ford I, Mills PR. High dose atorvastatin associated with increased risk of significant hepatotoxicity in comparison to simvastatin in UK GPRD cohort. PLoS One 2016; 11(3): e0151587

[18] Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63: 2889–2934

[19] Kim HS, Lee H, Park B, Park S, Kim H, Lee SH, Cho JH, Yoon KH, Cha BY, Kim JH, Choi IY. Comparative analysis of the efficacy of low- and moderate-intensity statins in Korea. Int J Clin Pharmacol Ther 2016; 54(11): 864–871

[20] Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D; Modification of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999; 130(6): 461–470

[21] National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39: S1–S266

[22] Centers for Disease Control and Prevention. Public health and aging: trends in aging—United States and worldwide. JAMA 2003; 289(11): 1371–1373

[23] Chae HB, Lee SY, Kim NH, Han KJ, Lee TH, Jang CM, Yoo KM, Park HJ, Lee MK, Jeon WS, Park SE, Moon HS, Park CY, Lee WY, Oh KW, Park SW, Rhee EJ. Age is the strongest effector for the relationship between estimated glomerular filtration rate and coronary artery calcification in apparently healthy Korean adults. Endocrinol Metab (Seoul) 2014; 29(3): 312–319

[24] Fang Q, Zou C, Zhong P, Lin F, Li W, Wang L, Zhang Y, Zheng C, Wang Y, Li X, Liang G. EGFR mediates hyperlipidemia-induced renal injury via regulating inflammation and oxidative stress: the detrimental role and mechanism of EGFR activation. Oncotarget 2016; 7(17): 24361–24373

[25] Campese VM, Nadim MK, Epstein M. Are 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors renoprotective? J Am Soc Nephrol 2005; 16(Suppl 1): S11–S17

[26] Verma A, Ranganna KM, Reddy RS, Verma M, Gordon NF. Effect of rosuvastatin on C-reactive protein and renal function in patients with chronic kidney disease. Am J Cardiol 2005; 96(9): 1290–1292

[27] Yasuda G, Kuji T, Hasegawa K, Ogawa N, Shimura G, Ando D, Umemura S. Safety and efficacy of fluvastatin in hyperlipidemic patients with chronic renal disease. Ren Fail 2004; 26(4): 411–418

[28] Gueler F, Rong S, Park JK, Fiebeler A, Menne J, Elger M, Mueller DN, Hampich F, Dechend R, Kunter U, Luft FC, Haller H. Postischemic acute renal failure is reduced by short-term statin treatment in a rat model. J Am Soc Nephrol 2002; 13(9): 2288–2298

[29] Sharyo S, Yokota-Ikeda N, Mori M, Kumagai K, Uchida K, Ito K, Burne-Taney MJ, Rabb H, Ikeda M. Pravastatin improves renal ischemia-reperfusion injury by inhibiting the mevalonate pathway. Kidney Int 2008; 74(5): 577–584

[30] Quintavalle C, Fiore D, De Micco F, Visconti G, Focaccio A, Golia B, Ricciardelli B, Donnarumma E, Bianco A, Zabatta MA, Troncone G, Colombo A, Briguori C, Condorelli G. Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury. Circulation 2012; 126(25): 3008–3016

[31] Shepherd J, Kastelein JJ, Bittner V, Deedwania P, Breazna A, Dobson S, Wilson DJ, Zuckerman A, Wenger NK; Treating to New Targets Investigators. Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study. Clin J Am Soc Nephrol 2007; 2(6): 1131–1139

[32] Nakamura H, Mizuno K, Ohashi Y, Yoshida T, Hirao K, Uchida Y; MEGA Study Group. Pravastatin and cardiovascular risk in moderate chronic kidney disease. Atherosclerosis 2009; 206(2): 512–517

[33] Kaneko H, Yajima J, Oikawa Y, Tanaka S, Fukamachi D, Suzuki S, Sagara K, Otsuka T, Matsuno S, Funada R, Kano H, Uejima T, Koike A, Nagashima K, Kirigaya H, Sawada H, Aizawa T, Yamashita T. Effects of statin treatment in patients with coronary artery disease and chronic kidney disease. Heart Vessels 2014; 29(1): 21–28

[34] Shah S, Paparello J, Danesh FR. Effects of statin therapy on the progression of chronic kidney disease. Adv Chronic Kidney Dis 2005; 12(2): 187–195

[35] Seliger SL, Weiss NS, Gillen DL, Kestenbaum B, Ball A, Sherrard DJ, Stehman-Breen CO. HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients. Kidney Int 2002; 61(1): 297–304

[36] Sakaeda T, Kadoyama K, Okuno Y. Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system. PLoS One 2011; 6(12): e28124

[37] de Zeeuw D, Anzalone DA, Cain VA, Cressman MD, Heerspink HJ, Molitoris BA, Monyak JT, Parving HH, Remuzzi G, Sowers JR, Vidt DG. Renal effects of atorvastatin and rosuvastatin in patients with diabetes who have progressive renal disease (PLANET I): a randomised clinical trial. Lancet Diabetes Endocrinol 2015; 3(3): 181–190

[38] Albert MA, Glynn RJ, Fonseca FA, Lorenzatti AJ, Ferdinand KC, MacFadyen JG, Ridker PM. Race, ethnicity, and the efficacy of rosuvastatin in primary prevention: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Am Heart J 2011; 162(1): 106–14.e2

[39] Kwon JE, Kim Y, Hyun S, Won H, Shin SY, Lee KJ, Kim SW, Kim TH, Kim CJ. Cholesterol lowering effects of low-dose statins in Korean patients. J Lipid Atheroscler 2014; 3(1): 21–28 (in Korean)

[40] Kim M, Kim HK, Ahn Y, Park H, Jeong MH, Cho JG, Park JC, Kim YJ, Cho MC, Kim CJ. Comparing high-intensity versus low-to moderate-intensity statin therapy in Korean patients with acute myocardial infarction. J Lipid Atheroscler 2014; 3(2): 97–104 (in Korean)

[41] Kim HS, Kim H, Jeong YJ, Kim TM, Yang SJ, Baik SJ, Lee SH, Cho JH, Choi IY, Yoon KH. Development of clinical data mart of HMG-CoA r(HMG-CoA) Reductase inhibitor for varied clinical research. Endocrinol Metab (Seoul) 2017; 32(1): 90–98

[42] Cho KW, Kim SM, An CH, Chae YM. Diffusion of electronic medical record based public hospital information systems. Healthc Inform Res 2015; 21(3): 175–183

Acknowledgements

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (No. HC15C1362).

Compliance with ethics guidelines

Seo Yeon Baik, Hyunah Kim, So Jung Yang, Tong Min Kim, Seung-Hwan Lee, Jae Hyoung Cho, Hyunyong Lee, Hyeon Woo Yim, Kun-Ho Yoon, and Hun-Sung Kim declare they have no conflicts of interests. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. This research was also approved by the International Review Board of Seoul St. Mary’s Hospital (KIRB-00465-005). Written informed consent was obtained from all patients included in the study.

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