POS-384 Brief angiotensin converting enzyme inhibition early in life improves renal functional reserve at 8 months of age in sheep born with a solitary functioning kidney

Abstract

Children born with solitary functioning kidney (SFK) have an increased risk of hypertension and kidney injury early in adulthood. Both hypertrophy and hyperfiltration are compensatory adaptations that occur in response to the loss of a kidney but may also contribute to kidney injury over time. Renal functional reserve (RFR), which is the difference between stimulated glomerular filtration rate (GFR) and basal GFR, may be absent or diminished in states of hyperfiltration. In addition, angiotensin-converting enzyme inhibitors (ACEi) have benefits in reducing hyperfiltration-mediated injury. Therefore, we hypothesised that owing to greater degree of hyperfiltration RFR would be reduced in SFK and improve with brief postnatal ACEi. SFK was induced by unilateral nephrectomy in male sheep fetuses at 100 days gestation (term=150 days; n=15) or sham surgery performed (sham, n=6). Between 4 to 8 weeks, SFK lambs received enalapril (SFK+ACEi; n=8; 0.5mg/kg/day, once daily, orally) or vehicle (water; SFK, n=7). Then at 8 months of age mean arterial pressure (MAP), glomerular filtration rate (GFR) and urinary protein excretion (UprotV) were measured in response to combined infusion of amino acid (0.065ml/kg/h) and dopamine (5µg/kg/min) (AA+D) in conscious lambs. In response to AA+D, MAP did not change in all groups. GFR increased in response to AA+D and this increase was less in SFK compared to sham and SFK+ACEi groups (%ΔGFR; sham: 314, SFK: 153, SFK+ACEi: 295). In response to AA+D UprotV increased in all groups, this increase was less in the SFK compared to the sham but similar to the SFK+ACEi sheep (%Δ UprotV; sham: 58574, SFK: 22847, SFK+ACEi: 31551). Acute amino acid and dopamine infusion revealed that SFK sheep have a reduced RFR, which may indicate they are in a state of hyperfiltration. Brief postnatal ACEi, by improving RFR and thus hyperfiltration, may alter the trajectory of renal and cardiovascular disease in children born with a SFK.