Abstract
BACKGROUND: Rapid glomerular filtration rate (GFR) decline (>3 mL/min/1.73 m(2)) is an increasingly recognized high-risk diabetic nephropathy (DN) phenotype in Type 1 diabetes. Rapid GFR decline is a recognized predictor of impaired GFR (<60 mL/min/1.73 m(2)). However, the association between rapid GFR decline and renal hyperfiltration is not well described in Type 1 diabetes. We hypothesized that renal hyperfiltration (estimated glomerular filtration rate, eGFR ≥ 120 mL/min/1.73 m(2)) would predict rapid GFR decline over 6 years and that rapid GFR decline would predict impaired GFR at 6 years in adults with Type 1 diabetes. METHODS: GFR was calculated by chronic kidney disease epidemiology (CKD-EPI) creatinine in 646 adults with Type 1 diabetes in the coronary artery calcification in Type 1 diabetes study. Logistic multivariable models were employed to investigate the relationships between renal hyperfiltration and rapid GFR decline, and rapid GFR decline and incident impaired GFR over 6 years. RESULTS: Renal hyperfiltration predicted greater odds of rapid GFR decline over 6 years [odds ratio (OR): 5.00, 95% confidence interval (CI): 3.03-8.25, P < 0.0001] adjusting for hemoglobin A1c (HbA1c), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), sex, duration, log of albumin/creatinine ratio and estimated insulin sensitivity. Furthermore, rapid GFR decline predicted greater odds of incident impaired eGFR (OR: 15.99, 95% CI 2.34-114.37, P = 0.006) in a similarly adjusted model. Sensitivity analyses with GFR calculated by CKD-EPI combined creatinine and cystatin C, and renal hyperfiltration defined as ≥135 mL/min/1.73 m(2) yielded similar results. CONCLUSIONS: In adults with Type 1 diabetes, rapid GFR decline over 6 years was associated with baseline renal hyperfiltration and incident GFR impairment. These observations may suggest an intermediate and predictive role of rapid GFR decline in the progression of DN.