Renal Outcomes of Triglyceride-Targeting Lipid-Lowering Therapies versus Statins in Patients with CKD

Background: Dyslipidemia, distinctly characterized by hypertriglyceridemia and impaired high-density lipoprotein cholesterol (HDL-C) metabolism in patients with chronic kidney disease (CKD), is associated with kidney disease progression. However, evidence on the renal outcomes of Triglyceride (TG)-targeting lipid-lowering therapies (LLTs), such as fibrates and niacin, often prescribed to patients with non-dialysis-dependent (NDD) CKD, is insufficient and equivocal. Methods: We designed this retrospective cohort study using a target trial emulation framework and leveraged data from a nationwide cohort of 3,562,882 US Veterans to identify incident CKD patients initiating de novo LLTs. We compared eGFR decline from baseline and the odds of rapid eGFR decline in fibrate and niacin initiators versus statin initiators using the mixed-effects model-predicted 1-year, 3-year, and 10-year eGFR slopes, adjusted for baseline covariates. We also compared the risk of major adverse kidney events [MAKE] (composite of a sustained ≥57% decrease in eGFR from baseline, sustained eGFR<15 mL/min/1.73 m 2 , incident end-stage renal disease, and all-cause death) using Cox proportional hazards models adjusted for baseline covariates during follow-up of up to 10 years. Results: Among 68,073 patients with incident CKD, 62,866 initiated de novo statin, 3,202 fibrate, or 2,005 niacin therapy. Compared to statin use, de novo fibrate initiators had slower eGFR decline (difference in 10-year slope: 0.26 mL/min/1.73 m 2 /year [95% CI, 0.11, 0.40], P<0.001), whereas the eGFR decline was not statistically significant in the niacin vs. statin comparison. The risk of MAKE was not significantly different in fibrate (hazard ratio, 0.94 [95% CI, 0.88, 1.01], P=0.09) or niacin (0.96 [0.89, 1.04], P=0.31) users after a median follow-up of 3.69 years. Conclusions: Among patients with NDD-CKD, unlike niacin, long-term fibrate use (compared to statin use) was associated with slower eGFR decline, suggesting renoprotective effects of fibrates. Further studies are warranted to investigate whether fibrate use is beneficial for preventing other outcomes, such as adverse cardiovascular events.