Effect of uric acid and estimated glomerular filtration rate on the Fibrosis-4 index

Hepatic steatosis and fibrosis present a significant public health burden, especially in China. Emerging evidence suggests an association between liver fibrosis and kidney function, indicating a potential relationship among uric acid (UA) levels, estimated glomerular filtration rate (eGFR), and the Fibrosis-4 (FIB-4) index. This retrospective cohort study investigates the correlation between UA, estimated GFR, and FIB-4 index in Chinese adults with metabolic dysfunction-associated steatotic liver disease (MASLD) using cross-sectional and longitudinal analyses. A total of 5051 adults with MASLD were included from 8857 individuals initially screened at the International Healthcare Center, Fourth Affiliated Hospital, Zhejiang University School of Medicine. The main outcome measure was the FIB-4 index. Among the 5051 participants (75.4% male; mean age, 42.3 years), the mean baseline eGFR was 98.7 mL/min/1.73 m2. Participants with lower eGFR had significantly older age and higher body mass index, systolic blood pressure, triglycerides, UA levels, and FIB-4 index than those with higher eGFR (P < .001 for all). In multivariable Cox regression analyses, each 1-standard deviation decrease in eGFR was associated with a 21% higher risk of an increased FIB-4 index (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.14-1.29; P < .001). Hyperuricemia (UA ≥ 420 μmol/L) was independently associated with a 38% higher risk of elevated FIB-4 (HR, 1.38; 95% CI: 1.23-1.55; P < .001). In the unadjusted model, a significant nonlinear dose-response relationship was observed between eGFR and FIB-4 (P for nonlinear trend < .001). However, after progressive adjustment for demographic variables, family history, and metabolic covariates, the nonlinear signal was markedly attenuated. Mediation analysis demonstrated that UA partially mediated the association between eGFR and FIB-4, accounting for 6.88% of the total effect. Reduced eGFR and hyperuricemia were independently associated with an elevated FIB-4 index in adults with MASLD, with a nonlinear relationship indicating a greater liver fibrosis risk in individuals with moderate to severe renal impairment (eGFR < 60 mL/min/1.73 m2). Partial mediation by UA suggests that metabolic dysregulation contributes to the kidney-liver interaction. Routine assessment of eGFR and UA may improve liver fibrosis risk stratification in patients with MASLD.