BRIEF ANGIOTENSIN CONVERTING ENZYME INHIBITION EARLY IN LIFE DELAYS THE ONSET OF ALBUMINURIA IN SHEEP BORN WITH A SOLITARY FUNCTIONING KIDNEY

Z MCARDLE¹, R SINGH¹, K MORITZ², M SCHREUDER³, K M DENTON¹

¹Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Australia, ²Child Health Research Centre and School of Biomedical Sciences, University of Queensland, Brisbane, Australia, ³Department of Pediatric Nephrology, Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands

Children with solitary functioning kidney (SFK) have an increased risk of hypertension and kidney injury from early in life. Hypertrophy and hyperfiltration are compensatory adaptations in the remaining kidney that may contribute to kidney injury over time. Angiotensin-converting enzyme inhibitors (ACEi) have reno-protective and blood pressure (BP) lowering properties. This study examined if brief ACEi early in life in sheep born with a SFK altered compensatory kidney hypertrophy and prevented elevation in BP and albuminuria. SFK was induced by unilateral nephrectomy in male fetal sheep at 100 days gestation (term=150 days; n=19) or sham surgery performed (n=10). Between 4 to 8 weeks, some SFK lambs received enalapril (n=10; 0.5mg/kg/day, once daily, orally) and others received vehicle (water; n=9). At 2, 6 and 20 months kidney volume was assessed using magnetic resonance imaging. At 8, 14 and 20 months, BP and urine albumin levels were examined. In SFK sheep, kidney volume was lower (~20%) than sham at 2 and 6 months but similar at 20 months. ACEi in SFK sheep reduced kidney volume at 2 months (~13%) but not at 6 or 20 months. SFK sheep had higher BP than sham at all ages and ACEi did not prevent the rise in BP. SFK sheep had higher urinary albumin at all ages compared with sham. ACEi prevented albuminuria at 8 months in sheep with SFK but not at 14 and 20 months.  In conclusion, brief and early ACEi in sheep with SFK did not prevent elevations in BP but delayed the onset of kidney injury in the short-term. This was likely associated with a reduction in the level of kidney hypertrophy early in life.

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