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Am J Physiol Renal Physiol 281: F887-F899, 2001. First published August 9, 2001; doi:10.1152/ajprenal.0050.2001
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Vol. 281, Issue 5, F887-F899, November 2001

Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function

David P. Basile, Deborah Donohoe, Kelly Roethe, and Jeffrey L. Osborn

Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

First published August 9, 2001; 10.1152/ajprenal.00050.2001.---Acute episodes of severe renal ischemia result in acute renal failure (ARF). These episodes are followed by a characteristic recovery and repair response, whereby tubular morphology and renal function appear completely restored within ~1 mo. However, the chronic effects of such an injury have not been well studied. Male rats were subjected to 60-min bilateral ischemia followed by reperfusion, yielding a characteristic injury. Postischemic animals manifested severe diuresis, peaking at 1 wk postinjury (volume: >45 ml/day, ARF vs. 18 ml/day, sham; P < 0.05). Urine flow subsequently declined but remained significantly elevated vs. sham animals for a 40-wk period. The prolonged alteration in urinary concentrating ability was attributable, in part, to a diminished capacity to generate a hypertonic medullary interstitium. By week 16, proteinuria developed in the post-ARF group and progressed for the duration of the study. Histological examination revealed essentially normal tubular morphology at 4 and 8 wk postinjury but the development of tubulointerstitial fibrosis at 40 wk. Transforming growth factor (TGF)-beta 1 expression was elevated at 40 wk, but not at 4 and 8 wk postinjury. Microfil analysis revealed an ~30-50% reduction in peritubular capillary density in the inner stripe of the outer medulla at 4, 8, and 40 wk in post-ARF groups vs. sham animals. In addition, post-ARF rats manifested a significant pressor response to a low dose of ANG II (15 ng · kg-1 · min-1). We hypothesize that severe ischemic injury results in a permanent alteration of renal capillary density, contributing to a urinary concentrating defect and the predisposition toward the development of renal fibrosis.

acute renal failure; regeneration; chronic renal failure; fibrosis; proteinuria; diuresis


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