Beneficial effects of brief early life angiotensin-converting enzyme inhibition wane with time in sheep with solitary functioning kidney.

Abstract

A child with a congenital solitary functioning kidney (SFK) may develop kidney disease from early in life due to hyperfiltration injury. Previously, we showed in a sheep model of SFK that brief angiotensin-converting enzyme inhibition (ACEi) early in life is reno-protective and increases renal functional reserve (RFR) at 8 months of age. Here we investigated the long-term effects of brief early ACEi in SFK sheep out to 20 months of age. At 100 days gestation (term = 150 days) SFK was induced by fetal unilateral nephrectomy, or sham surgery was performed (controls). SFK lambs received enalapril (SFK+ACEi; 0.5 mg/kg, once daily, orally) or vehicle (SFK) from 4 to 8 weeks of age. At 8, 14 and 20 months of age urinary albumin excretion was measured. At 20 months of age, we examined basal kidney function and RFR via infusion of combined amino acid and dopamine (AA+D). SFK+ACEi resulted in lower albuminuria (∼40%) at 8 months, but not at 14 or 20 months of age compared with vehicle-SFK. At 20 months, basal GFR (∼13%) was lower in SFK+ACEi compared with SFK, but renal blood flow (RBF), renal vascular resistance (RVR) and filtration fraction were similar to SFK. During AA+D, the increase in GFR was similar in SFK+ACEi and SFK animals, but the increase in RBF was greater (∼46%) in SFK+ACEi than SFK animals. Brief ACEi in SFK delayed kidney disease in the short-term but these effects were not sustained long-term.