Hepatic fibrosis severity assessed by FIB-4 index is independently associated with reduced kidney function in patients with metabolic dysfunction-associated steatotic liver disease: a nationwide multicenter study from Türkiye

Abstract

Background and aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic disorder associated with extrahepatic organ damage, including chronic kidney disease (CKD). The Fibrosis-4 (FIB-4) index is a validated non-invasive tool for estimating hepatic fibrosis severity. This study aimed to investigate whether FIB-4-defined hepatic fibrosis is independently associated with reduced estimated glomerular filtration rate (eGFR) in a large, real-world Turkish MASLD cohort. Methods This is a cross-sectional analysis of the prospective, nationwide, multicenter DAHUDER MASLD Study, which enrolled patients from 44 internal medicine outpatient clinics across 31 provinces representing all 12 statistical regions of T & uuml;rkiye. A total of 10,873 MASLD patients were included. MASLD was defined as ultrasonographic hepatic steatosis in the presence of at least one cardiometabolic risk factor. High FIB-4 was defined as >= 1.3 for patients aged < 65 years and >= 2.0 for those aged >= 65 years, per EASL-EASD-EASO 2024 guidelines. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Age-stratified multivariate linear regression models were constructed to identify independent predictors of eGFR. Results High FIB-4 was detected in 11.2% of the patients (n = 1219). Patients with high FIB-4 had significantly lower eGFR compared to those with low FIB-4 (85.37 +/- 21.08 vs. 94.18 +/- 20.17 mL/min/1.73 m(2), p < 0.001). FIB-4 score was negatively correlated with eGFR (r = - 0.149, p < 0.001). In age-stratified multivariate analysis adjusted for diabetes mellitus, hypertension, BMI, sex, SGLT2 inhibitor use, and uric acid, FIB-4 score remained an independent predictor of reduced eGFR in both age groups (< 65 years: B = - 2.586, 95% CI [- 3.025, - 2.148], p < 0.001; >= 65 years: B = - 1.384, 95% CI [- 2.326, - 0.443], p = 0.004). eGFR decreased progressively across cardiometabolic risk score categories, from approximately 105 mL/min/1.73 m(2) (score 1) to approximately 87 mL/min/1.73 m(2) (score 5). KDIGO-based staging revealed a higher prevalence of advanced CKD stages in the high FIB-4 group (p < 0.001). Conclusions Hepatic fibrosis severity, as quantified by the FIB-4 index, is independently associated with impaired kidney function in patients with MASLD beyond established cardiometabolic risk factors. These findings support the role of FIB-4 as a simple, cost-effective tool for integrated cardio-hepato-renal risk stratification. Clinicians should systematically monitor renal function in MASLD patients, particularly those with elevated FIB-4 scores.