Renal hypertrophy and hyperfiltration is enhanced in early acquired compared with a congenital solitary function kidney model in sheep

Abstract

A congenital solitary functioning kidney (C-SFK) or an early acquired SFK (EA-SFK), due to childhood unilateral nephrectomy (UNX), increases the risk of hypertension and kidney disease early in life. Evidence suggests that children with an EA-SFK may have a higher risk of future kidney disease compared with those with a C-SFK, but the precise underlying mechanisms need further investigation. C-SFK was induced by fetal UNX at 100 days gestation (term=150 days) in male sheep fetuses, and a sham procedure was performed. At approximately one month of age, EA-SFK was induced by UNX in male lambs. At eight months of age, total kidney weight was similar in all groups due to marked hypertrophy in the C-SFK and EA-SFK groups. Blood pressure was similar in EA-SFK and sham groups but ~12 mmHg higher in the C-SFK group compared with sham. Compared with the sham group, glomerular filtration rate (GFR) was ~9% less in the EA-SFK group and ~26% less in the C-SFK. GFR was ~23% higher in EA-SFK compared with the C-SFK group. Albuminuria was ~67% higher in C-SFK sheep but similar in the EA-SFK group compared with sham sheep. However, like the C-SFK group, the renal blood flow response to nitric oxide blockade was attenuated in the EA-SFK group compared with sham. In conclusion, long-term studies are needed to determine whether the higher hyperfiltration and disturbed vasodilator balance observed in EA-SFK sheep will cause an accelerated decline in renal function with aging.