Glomerular Hyperfiltration as a Sentinel Marker for Chronic Kidney Disease and Liver Fibrosis in MASLD/MAFLD: Longitudinal Evidence

Background: The interplay between glomerular hyperfiltration (GHF) and renal dysfunction and hepatic fibrosis in metabolic-associated steatotic (or fatty) liver disease (MASLD or MAFLD) remains insufficiently understood. Therefore, we examined the association in a relatively healthy population. Methods: Between 2002 and 2019, 47,741 adults (18–70 years old) participated in the study and underwent baseline liver ultrasonography and annual renal function assessments. Hepatic steatosis was diagnosed using ultrasonography, and GHF was defined as an estimated residual glomerular filtration rate exceeding the 95th percentile based on age- and sex-specific thresholds. The progression of liver fibrosis was assessed using noninvasive markers. Chronic kidney disease (CKD) and advanced liver fibrosis progression were the primary and secondary endpoints, respectively. Results: Patients with MASLD but without GHF did not exhibit an increased risk of CKD progression. However, GHF was independently associated with a higher risk of CKD progression, particularly in patients with MASLD (adjusted hazard ratio (HR): 3.88 [95% CI 3.66–4.11]). GHF alone led to a slight increase in advanced liver fibrosis risk, whereas its presence in patients with MASLD significantly exacerbated fibrosis progression (adjusted HR, 1.36 [95% CI 1.24–1.48]). In patients with coexisting GHF and MASLD, CKD development was associated with a 24% additional risk of advanced liver fibrosis (adjusted HR, 1.24; 95% CI, 1.19–1.29). Consistent findings were also noted based on the MAFLD definition. Conclusions: GHF is associated with future CKD and liver fibrosis progression, serving as a prognostic marker in patients with MASLD (or MAFLD), emphasizing the need for timely identification and monitoring.