Tubular leakage and obstruction after renal ischemia: Structural-functional correlations

J. F. Donohoe, M. A. Venkatachalam, D. B. Bernard, N. G. Levinsky

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181 Scopus citations


Ischemic sequelae were evaluated in rats following relief of 60, 25, and 15 min of renal artery occlusion. Light/electron microscopy after 60 min's ischemia showed necrosis of isolated cells in both proximal convoluted (PCT) and proximal straight tubules (PST); necrosis was present only in PST with 25 min's ischemia. Thirty-five percent of 14C-inulin microinjected into ischemic PCT was recovered in contralateral urine after 60 min of ischemia; 11% was recovered after 25 min. Backleak was insignificant after 15 min of ischemia. Horseradish peroxidase (mol wt, 40,000), injected into PCT passed through the cytoplasm of tubular cells into the interstitium. Intravenous administration of peroxidase demonstrated that loss of selective permeability of tubular cells to large molecules was not an artefact of tubular injection techniques. Intrarenal inulin sequestration was used as an approximate index of obstruction. After 60 min of ischemia, 28% of microinjected inulin was not recovered in urine from either kidney; after 25 min of ischemia, non-recovery was 12%. About three-quarters of this missing inulin was recovered from the ischemic kidney itself. Recovery in urine was substantially complete in control and 15 min's-ischemic animals. Impacted swollen blebs of brush border were seen in > 75% of PST following 60 min of ischemia, whereas this phenomenon was much less frequent and evanescent after 25 min. We conclude that increasing duration of renal ischemia causes incremental tubular leakiness to large molecules, which diffuse through damaged cells. After 60 min of ischemia, most PST appear filled with impacted brush border, which may cause obstruction.

Original languageEnglish (US)
Pages (from-to)208-222
Number of pages15
JournalKidney international
Issue number3
StatePublished - 1978
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology


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