Long-term prospective observation suggests that glomerular hyperfiltration is associated with rapid decline in renal filtration function: A multiethnic study

Aim: Glomerular hyperfiltration usually occurs early in development of kidney complications in diabetes. To understand hyperfiltration as a marker of renal disease progression in type 2 diabetes mellitus, we aimed to examine association between glomerular hyperfiltration (estimated glomerular filtration rate120mL/min/1.73 m(2)) and rapid renal decline (annual estimated glomerular filtration rate loss3mL/min/1.73 m(2)). Methods: This was a prospective cohort comprising 1014 patients with type 2 diabetes mellitus attending a Diabetes Centre of a regional hospital in 2002-2014. A separate prospective cohort, comprising 491 patients who attended Diabetes Centre or primary-care polyclinics, was used for validation. We performed binary mediation analysis to examine role of hyperfiltration on relationship between baseline haemoglobin A1c and rapid renal decline. Results: Among patients in discovery cohort, 5.2% had baseline hyperfiltration. Over mean follow-up of 6years, 22.9% had rapid glomerular filtration rate decline. Baseline hyperfiltration was significantly associated with greater odds of rapid renal decline after adjusting for demographics, diabetes duration and clinical covariates (odds ratio: 2.57; 95% confidence interval: 1.21-5.46; p = 0.014). Similar finding was found in validation cohort (odds ratio: 2.98; 95% confidence interval: 1.06-8.42; p = 0.034). Hyperfiltration significantly accounted for 35.3% of association between increasing baseline haemoglobin A1c and rapid renal decline. Conclusion: Glomerular hyperfiltration is an independent risk factor of rapid renal decline. It mediates the association between increasing haemoglobin A1c and rapid renal decline.