POS-394 SOLITARY FUNCITONING KIDNEY ACQUIRED EARLY IN LIFE IS NOT ASSOCIATED WITH REDUCED RENAL FUNCTIONAL RESERVE COMPARED WITH CONGENITAL SOLITARY FUNCTIONING KIDNEY IN SHEEP

Abstract

Children born with a solitary functioning kidney (SFK) can develop hypertension and kidney injury. Children who acquire a SFK early in childhood (early acquired; EA-SFK) have a greater incidence of kidney injury compared with those with a congenital SFK (C-SFK). The mechanisms underlying these differences are not well understood. The C-SFK undergoes compensatory nephron hyperplasia. Since no new nephrons form after birth in humans, the degree of nephron deficiency is greater in the EA-SFK compared with C-SFK. In both forms of SFK, the remaining kidney undergoes hypertrophy and increases glomerular filtration rate (GFR) to compensate for the loss of a kidney but this hyperfiltration can promote kidney injury. We hypothesized that owing to greater degree of nephron deficiency, the EA-SFK would undergo a greater a degree of hyperfiltration compared with C-SFK. Additionally, we hypothesized that owing to greater degree of basal hyperfiltration, in response to a challenge, EA-SFK would have a reduced capacity to increase renal functional reserve. Unilateral nephrectomy was performed in sheep fetus at 100 days of gestation (term-150 days; n=9) to induce C-SFK and in the 4-week-old lamb (n=8) to induce EA-SFK. Like the human, no new nephrons form after birth in the sheep. At 8 months of age, mean arterial pressure (MAP), GFR, and urinary protein excretion (UprotV) were measured during an hour baseline and during 120 minutes of a combined infusion of amino acid (0.065ml/kg/h) and dopamine (5µg/kg/min) (AA+DOPA) in conscious lambs. Basal MAP was ~10mmHg lower in the EA-SFK group compared with C-SFK (P=0.003) and basal UprotV was ~50% lower in the EA-SFK compared with C-SFK group (P=0.0003). Basal GFR was ~27% greater in the EA-SFK compared with C-SFK group. In response to AA+DOPA, MAP did not change but UprotV and GFR increased from baseline in both groups. The increase in GFR in EA-SFK group was ~21% greater than the C-SFK group (P=0.08) but the increase in UprotV was similar between the groups. EA-SFK group had higher basal GFR compared with C-SFK demonstrating evidence of hyperfiltration. However, this was not associated with a reduced capacity to increase GFR in response to a combined infusion of amino acid and dopamine. Longer term follow-up maybe needed to determine if the greater basal GFR observed in the EA-SFK group exacerbates kidney injury and causes loss of renal functional reserve overtime.