Glomerular hyperfiltration defined by eGFR and long-term clinical outcomes: a systematic review and meta-analysis

Background: Glomerular hyperfiltration (GHF) has been widely recognized as a potential risk factor. However, current evidence regarding both its precise definition and clinical prognostic value remains inconclusive. Methods: We systematically searched PubMed, Embase, and the Cochrane Library, as well as reference lists of relevant articles. Cohort studies examining the association between eGFR-defined GHF and clinical outcomes were included, and meta-analyses were conducted using a random-effects model. Cross-sectional studies and data from the National Health and Nutrition Examination Survey (NHANES) were used to estimate and compare the 95th percentile of eGFR in healthy populations in China and the United States. Results: . A total of 17 studies, including 11,563,332 participants, were included in the systematic review. GHF was significantly associated with an increased risk of all-cause mortality (HR, 1.30; 95% CI, 1.18-1.42) and incident albuminuria (HR, 1.43; 95% CI, 1.05-1.93) but was not significantly associated with cardiovascular disease. In addition, individual studies suggested potential associations between GHF and rapid eGFR decline, the incident dementia, and the incident non-alcoholic fatty liver disease. Conclusion: Although eGFR is subject to measurement biases in non-CKD populations, extremely high values may still indicate underlying risks not captured by routine monitoring. This study provides reference values for the 95th percentile of eGFR in the general Chinese and American populations and underscores the need to validate individualized definitions of GHF. Given the limited and heterogeneous evidence base, these findings should be interpreted cautiously, and further prospective studies are needed to clarify the clinical significance of GHF. Systematic review registration: INPLASY 202540039.