Contralateral nephrectomy‐induced improvement in renal structure and function following unilateral ischemia‐reperfusion injury is counter intuitively associated with markers of renal hypoxia (890.5)

Abstract

Unilateral ischemia‐reperfusion injury (UIRI) leads to progressive renal atrophy and tubulointerstitial fibrosis (TIF). However, contralateral nephrectomy (CNX) 2 wks post UIRI can improve renal function and reverse TIF via poorly defined mechanisms. We examined the renal hemodynamic, structural and hypoxia signaling correlates associated with UIRI and its reversal by CNX. Two wks after 60 min UIRI or sham UIRI, BP (radiotelemetry), left RBF (Transonic) and 24 hr GFR measurements (FITC‐inulin, osmotic minipumps) were made in conscious rats and then repeated every 2‐3 days for 2 wks following CNX or sham CNX. In the presence of a contralateral uninjured kidney, RBF (ml/min) was reduced (P<0.05) in UIRI (4.1±0.4) vs. sham UIRI (9.3±0.8) kidneys. Without CNX, extensive renal atrophy, TIF, and tubule dedifferentiation, but minimal pimonidazole and HIF‐1α positivity, were present at 4 wks post UIRI. Conversely, CNX increased (P<0.05) GFR (ml/min) from 0.8±0.1 to 1.3±0.1 over 2 wks and led to sustained increases (P<0.05) in RBF (6.2±0.6 ml/min). CNX‐induced improvement in renal function was associated with renal hypertrophy, more redifferentiated tubules, less TIF and robust pimonidazole and HIF‐1α staining in UIRI kidneys. We conclude that TIF at 4 wks post UIRI without CNX is not associated with indices of hypoxia, which, unexpectedly correlated with recovery of renal function/structure and reversal of TIF following CNX.Grant Funding Source: Supported by Veterans Administration, National Institute of Health, National Kidney Foundation of IL