Hepatorenal vulnerability flagged by glomerular hyperfiltration in metabolic liver disease: a large health-screening cohort evidence

The interplay between glomerular hyperfiltration (GHF) and downstream renal dysfunction and hepatic fibrosis in metabolic dysfunction–associated steatotic (or fatty) liver disease (MASLD or MAFLD) remains insufficiently understood. We investigated these associations in a large cohort of generally healthy adults with a low prevalence of obesity. In a longitudinal health-screening cohort, 47,741 adults aged 18–70 years were followed from 2002 to 2019, with baseline liver ultrasonography and annual renal assessments. Hepatic steatosis was diagnosed by ultrasonography. GHF was defined as a residual estimated glomerular filtration rate (eGFR) above the age- and sex-specific 95th percentile. Chronic kidney disease (CKD) progression was defined by eGFR-based criteria only because urinary albumin-creatinine ratio was frequently missing. The primary endpoint was CKD progression; the secondary endpoint was progression to advanced liver fibrosis, assessed using noninvasive markers. In fully adjusted models for CKD progression, GHF was an independent risk factor irrespective of MASLD status (hazard ratio, 3.55; 95% CI, 3.37–3.73). Whereas MASLD itself showed no material increase in risk (0.92; 95% CI, 0.89–0.96) when adjusted for confounders, particularly hyperfiltration. The relative risk of CKD progression was higher in individuals with GHF alone than in those with both MASLD and GHF (adjusted HR 3.88, 95% CI 3.66–4.11 vs. 2.56, 95% CI 2.30–2.86). For advanced liver fibrosis, MASLD was an independent risk factor regardless of GHF (1.20; 95% CI, 1.17–1.23), while GHF itself was associated with only a modest increase (1.09; 95% CI, 1.04–1.14): combined MASLD + GHF further amplified risk (1.36; 95% CI, 1.24–1.48). Among individuals with both MASLD and GHF, those who experienced CKD progression exhibited a higher subsequent risk of advanced liver fibrosis than those without CKD progression (1.17 [95% CI, 1.13–1.20] vs. 1.24 [95% CI, 1.19–1.29]). Results were consistent when applying MAFLD criteria. Glomerular hyperfiltration signals heightened hepatorenal vulnerability; it is associated with increased risks of CKD progression and advanced liver fibrosis—particularly in MASLD—and may inform clinical risk stratification, although causal inference is limited by the retrospective, observational design.