Modulation of the Renal Response to ACE Inhibition by ACE Insertion/Deletion Polymorphism During Hyperglycemia in Normotensive, Normoalbuminuric Type 1 Diabetic Patients

Abstract

ACE inhibition protects kidney function, but ACE insertion/deletion (I/D) polymorphism affects renal prognosis in type 1 diabetic patients. ACE genotype may influence the renal benefits of ACE inhibition. We studied the impact of ACE I/D polymorphism on the renal hemodynamic changes induced by ACE inhibition in type 1 diabetes. We studied renal hemodynamics (glomerular filtration rate [GFR], effective renal plasma flow [ERPF], filtration fraction [GFR/ERPF], mean arterial pressure [MAP], and total renal resistances [MAP/ERPF]) repeatedly during normoglycemia and then hyperglycemia in 12 normotensive, normoalbuminuric type 1 diabetes and the II genotype (associated with nephroprotection) versus 22 age- and sex-matched subjects with the ACE D allele after three randomly allocated 2- to 6-week periods on placebo, 1.25 mg/day ramipril, and 5 mg/day ramipril in a double-blind, cross-over study. During normoglycemia, the hemodynamic changes induced by ramipril were similar in both genotypes. During hyperglycemia, the changes induced by ramipril were accentuated in the II genotype group and attenuated dose dependently in the D allele group (treatment-genotype interaction P values for ERPF, 0.018; MAP, 0.018; and total renal resistances, 0.055). These results provide a basis to different renal responses to ACE inhibition according to ACE genotype in type 1 diabetes.