Abstract
INTRODUCTION: Marine n-3 polyunsaturated fatty acids (PUFAs) are proposed to have ameliorative effects on kidney function, but their role in type 2 diabetes (T2D)-related kidney disease remains uncertain.
OBJECTIVES: In this study, we assessed the protective effect of marine n-3 PUFAs against worsening renal function in T2D patients and explored the underlying mechanisms.
METHODS: Individuals with T2D in UK biobank were included to examine associations between circulating fatty acids and incident chronic kidney disease (CKD). The PNMD trial (NCT03708887) is a 14-month randomized, double-blind, placebo-controlled trial evaluating dose-dependent effects of marine n-3 PUFAs on renal function in T2D.
RESULTS: In a cohort of 5,856 diabetic patients, higher plasma levels of n-3 PUFAs were associated with a 22% reduction in the risk of developing CKD. RCT involving 415 T2D patients reported that high-dose n-3 PUFA (3 g/day) supplementation significantly improved estimated glomerular filtration rate (eGFR) compared with placebo. The protective effect of n-3 PUFA supplementation against worsening renal function among T2D patients was primarily mediated by HDL-4-Apo-A2, a key subclass of high-density lipoproteins and was more pronounced in patients with the Apo-A1 related rs10419198 TT/CT genotype. Using the db/db/fat-1 transgenic mice, we unraveled endogenous n-3 PUFAs advances renal function by modulating lipid metabolism and promoting cholesterol efflux through the Sirt1-PGC1α-ABCA1 pathway.
CONCLUSION: These findings provide novel insights into the protective role of marine n-3 PUFAs in preserving impaired kidney function in T2D, underscoring their potential as a therapeutic strategy for diabetic kidney disease.