Brief Early Life Angiotensin-Converting Enzyme Inhibition Offers Renoprotection in Sheep with a Solitary Functioning Kidney at 8 Months of Age

Zoe McArdle, Reetu R. Singh, Helle Bielefeldt-Ohmann, Karen M. Moritz, Michiel F. Schreuder, Kate M. Denton

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Background Children born with a solitary functioning kidney (SFK) are predisposed to develop hypertension and kidney injury. Glomerular hyperfiltration and hypertrophy contribute to the pathophysiology of kidney injury. Angiotensin-converting enzyme inhibition (ACEi) can mitigate hyperfiltration and may be therapeutically beneficial in reducing progression of kidney injury in those with an SFK. Methods SFK was induced in male sheep fetuses at 100 days gestation (term5150 days). Between 4 and 8 weeks of age, SFK lambs received enalapril (SFK1ACEi; 0.5mg/kg per day, once daily, orally) or vehicle (SFK). At 8 months, we examined BP, basal kidney function, renal functional reserve (RFR; GFR response to combined amino acid and dopamine infusion), GFR response to nitric oxide synthase (NOS) inhibition, and basal nitric oxide (NO) bioavailability (basal urinary total nitrate and nitrite [NOx]). Results SFK1ACEi prevented albuminuria and resulted in lower basal GFR (16%), higher renal blood flow (approximately 22%), and lower filtration fraction (approximately 35%), but similar BP, compared with vehicle-treated SFK sheep. Together with greater recruitment of RFR (approximately 14%) in SFK1ACEi than SFK animals, this indicates a reduction in glomerular hyperfiltration-mediated kidney dysfunction. During NOS inhibition, the decrease in GFR (approximately 14%) was greater among SFK1ACEi than among SFK animals. Increased (approximately 85%) basal urinary total NOx in SFK1ACEi compared with SFK animals indicates elevated NO bioavailability likely contributed to improvements in kidney function and prevention of albuminuria. Conclusions Brief and early ACEi in SFK is associated with reduced glomerular hyperfiltration-mediated kidney disease up to 8 months of age in a sheep model.

Original languageEnglish
Pages (from-to)1341-1356
Number of pages16
JournalJournal of the American Society of Nephrology
Issue number7
Publication statusPublished - Jul 2022

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