The Separate Contributions of Visceral Fat and Liver Fat to Chronic Kidney Disease-Related Renal Outcomes

Objectives This study aims to investigate the separate contributions of liver fat and visceral fat on microalbuminuria and impaired renal function, and second, to examine whether non-alcoholic fatty liver disease is causally related to microalbuminuria and/or impaired renal function. Methods Associations between visceral adipose tissue (VAT), hepatic triglyceride content (HTGC), and risk of microalbuminuria and renal function were studied cross-sectionally in the Netherlands Epidemiology of Obesity study. Mendelian randomization using GWAS meta-analysis data was performed to estimate the causal effect of non-alcoholic fatty liver disease (PNPLA3, LYPLAL1, NCAN, GCKR) on eGFR (N max 118,460), microalbuminuria (N max 54,116), and impaired renal function (N max 118,147). Results In total, 2,023 participants (mean age 55.5 ± 6.0 years, 53% women) were included of which 29% had fatty liver and 2.0% chronic kidney disease stage ≥3. In joint models, VAT was associated with a 2-fold increased risk of microalbuminuria which was mainly driven by the association in women (total population: per standard deviation [SD] = 55.4 cm2, odds ratio [OR] 2.02, 95% confidence interval [CI] 1.18-3.47; women: OR 2.83, 95% CI 1.44, 5.56), but HTGC was not (total population: per SD = 7.9%, OR 1.20, 95% CI 0.85, 1.70). No associations were found for VAT and HTGC with eGFR (VAT: per SD = 55.4 cm2, OR 1.25, 95% CI 0.83, 1.87; HTGC: per SD = 7.9%, OR 0.65, 95% CI 0.42, 0.99). No causal effect of NAFLD on microalbuminuria or impaired renal function was found. Conclusions In observational analyses, visceral fat was associated with microalbuminuria in women. Liver fat was not associated with microalbuminuria or renal function, which was supported by Mendelian randomization. Visceral fat might be more important than liver fat in the etiology of microalbuminuria.