Insulin-resistance hyperinsulinemia is a novel risk factor for renal disease in the general population. Glomerular hyperfiltration has been proposed as an early consequence of hyperinsulinemia.In this multicenter cohort study, we analyzed 202 patients without diabetes before or after renal transplantation during the first posttransplant year. Insulin was measured at 3 and 12 months. The majority of patients (91%) were on calcineurin inhibitors. Patients were classified as with persistent normo or hyperinsulinemia when situated below or above the median value of insulin (3 months: 9 muU/mL; 12 months: 8.74 muU/mL) at both periods. The 3 to 12 months percent change in calculated creatinine clearance (3-12 months DeltaCrCL) was calculated.Patients with persistent hyperinsulinemia showed a higher increase in 3 to 12 months DeltaCrCL compared with those with persistent normoinsulinemia (12% [-20/40] vs. -0.03% [-12/18], P=0.035). We performed a multivariate linear regression analysis with the 3 to 12 months DeltaCrCL as the dependent variable and different factors that may induce hyperfiltration, including persistent hyperinsulinemia, as covariates. Persistent hyperinsulinemia was a risk factor for increased CrCL (beta 0.09, 95% CI 0.07/0.12, P=0.035).In nondiabetic recipients during the first posttransplant year, hyperinsulinemia induced increments in CrCL. As this may herald future renal dysfunction, hyperinsulinemia should not be ignored as a potential target in this population.