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

D. P. Basile, D. Donohoe, K. Roethe, J. L. Osborn

Research output: Contribution to journalArticlepeer-review

503 Scopus citations

Abstract

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)-β1 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.

Original languageEnglish (US)
Pages (from-to)F887-F899
JournalAmerican Journal of Physiology - Renal Physiology
Volume281
Issue number5 50-5
StatePublished - Dec 19 2001
Externally publishedYes

Keywords

  • Acute renal failure
  • Chronic renal failure
  • Diuresis
  • Fibrosis
  • Proteinuria
  • Regeneration

ASJC Scopus subject areas

  • Physiology
  • Urology

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