Glomerular hyperfiltration in dipstick-negative type 2 diabetes mellitus: a novel determinant of kidney function decline in type 2 diabetes mellitus

Abstract

Background: The independent impact of type 2 diabetes mellitus (T2DM) on kidney outcomes beyond albuminuria remains unclear. We evaluated whether T2DM affects kidney outcomes in individuals with normal kidney function without albuminuria. Methods: Data from the National Health Insurance Service-National Sample Cohort of Korea (2009-2015) were analyzed. Individuals with normal kidney function were stratified by T2DM status. The primary outcome was a composite kidney outcome consisting of initiation of kidney replacement therapy and a sustained decline in estimated glomerular filtration rate (eGFR) of ≥40% from baseline. Results: Among 77,267 individuals with normal kidney function without albuminuria, patients with T2DM (n = 11,957) showed significantly steeper annual decline in eGFR than non-T2DM individuals (-0.113 mL/min per 1.73 m2 per year; 95% confidence interval [CI], -0.222 to -0.003). T2DM was associated with a 57% higher risk of composite kidney outcome (adjusted hazard ratio, 1.57; 95% CI, 1.28-1.92), independent of traditional risk factors. This association was strongest in individuals with glomerular hyperfiltration and longer T2DM duration (≥6 years). Conclusion: Normal kidney function T2DM was associated with accelerated kidney function decline and a 1.5-fold increased risk of adverse kidney outcomes compared with normal kidney function non-T2DM, particularly in individuals with glomerular hyperfiltration and longer duration.