Simvastatin reduces chronic kidney disease and renal failure risk in type 2 diabetes patients: post hoc ACCORD trial analysis

Jiaxi Pu; Ming Gao; Pan Yu; Jiaqi Tian; Junxia Yan; Qiongjing Yuan; Lijian Tao; Zhangzhe Peng

doi:10.1186/s13098-024-01514-6

Simvastatin reduces chronic kidney disease and renal failure risk in type 2 diabetes patients: post hoc ACCORD trial analysis

Diabetol Metab Syndr. 2024 Nov 14;16(1):272. doi: 10.1186/s13098-024-01514-6.

Authors

Jiaxi Pu¹, Ming Gao², Pan Yu¹, Jiaqi Tian³, Junxia Yan⁴, Qiongjing Yuan¹, Lijian Tao¹, Zhangzhe Peng⁵

Affiliations

¹ Department of Nephrology, Xiangya Hospital, Central South University, Changsha, 410008, China.
² Department of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital, Central South University, Changsha, 410008, China.
³ Alibaba Cloud, Alibaba Group, Hangzhou, 311121, China.
⁴ Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, 410008, China.
⁵ Department of Nephrology, Xiangya Hospital, Central South University, Changsha, 410008, China. pengzhangzhe@csu.edu.cn.

Abstract

Objective: Type 2 diabetes mellitus (T2DM) poses a substantial global health concern. Statins are widely used among T2DM patients for managing dyslipidemia, preventing cardiovascular disease (CVD), and offering renal protection. However, the extent to which their renal protective effects contribute to reducing the incidence of severe renal complications, including chronic kidney disease (CKD) and renal failure, is not well-defined.

Methods: This investigation scrutinizes the impact of simvastatin versus placebo on renal outcomes among T2DM patients utilizing data from the ACCORD trial. It encompasses incidence rate comparisons, Kaplan-Meier estimates, Cox proportional hazards models, and mediation analyses.

Results: The study consisted of 3,619 individuals diagnosed with T2DM, among which 2,753 were treated routinely with simvastatin, while 866 did not receive any statin therapy. After adjusting for baseline characteristics and time-dependent covariates, simvastatin treatment was associated with a 71% reduction in the risk of CKD (HR 0.29, 95% CI 0.27-0.31, p < 0.01) and a 47% reduction in the risk of renal failure (HR 0.53, 95% CI 0.44-0.65, p < 0.01) compared to the statin-free group. Further subgroup analysis, accounting for the initial lipid and kidney profiles, indicated variable impacts of simvastatin on CKD and renal failure outcomes. Nevertheless, a consistent reduction in CKD risk was observed across all subgroups within the statin-treated population. Additional mediation analysis revealed that the reduction in low-density lipoprotein cholesterol (LDL-C) may be a potential mediator in the association between simvastatin and CKD, with a mediation effect of 14.9%, (95% CI 0.11-0.19, p < 0.01).

Conclusion: Administering statins, specifically simvastatin, to T2DM patients at elevated risk for CVD, is likely to offer augmented renal advantages, notably in lowering the occurrence of CKD and renal failure. This protective effect against CKD manifests regardless of initial lipid profiles, albuminuria, and estimated glomerular filtration rate (eGFR) levels. The association between simvastatin and CKD may be partially mediated by LDL-C reduction.

Keywords: ACCORD; Chronic kidney disease; Renal failure; Simvastatin; Type 2 diabetes.

Abstract

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