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

Tubular leakage and obstruction after renal ischemia: Structural-functional correlations. These ischemic sequelae were evaluated in rats following relief of 60, 25, and 15min 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 25min's ischemia. Thirty-five percent of 14 C-inulin microinjected into ischemic PCT was recovered in contralateral urine after 60min of ischemia; 11% was recovered after 25min. Backleak was insignificant after 15min 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 60min of ischemia, 28% of microinjected inulin was not recovered in urine from either kidney; after 25min 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 15min's-ischemic animals. Impacted swollen blebs of brush border were seen in > 75% of PST following 60min of ischemia, whereas this phenomenon was much less frequent and evanescent after 25min. We conclude that increasing duration of renal ischemia causes incremental tubular leakiness to large molecules, which diffuse through damaged cells. After 60min of ischemia, most PST appear filled with impacted brush border, which may cause obstruction. Defaut d'etancheite tubulaire et obstruction apres ischemic renale: Correlations structuro-fonctionnelles. Les sequelles de l'ischemie ont ete evaluees chez le rat apres la levee, a la 60ame, 25eme ou 15eme minutes d'une occlusion de l'artere renale. La microscopie photonique et electronique apres 60 minutes d'ischemie montre des necroses de cellules isolees a la fois dans les tubes contournes proximaux (PCT) et dans les tubes droits proximaux (PST); la necrose n'apparait que dans PST apres 25 minutes d'ischemie. 35% de l'inuline- 14 C injectee dans PCT est recuperee dans l'urine controlaterale apres 60 minutes d'ischemie, 11% apres 25 minutes. Cette quantite est negligeable apres 15 minutes d'ischemie. La peroxydase de raifort (PM 40.000), injectee soit dans PCT soit par voie intraveineuse, passe a travers le cytoplasme des cellules tubulaires vers l'interstitium. L'administration par voie intraveineuse montre que la fuite tubulaire des grosses molecules n'est pas un artefact lie a l'injection tubulaire. La sequestration d'inuhne dans le rein a ete utilisee comme un index approximatif de l'obstruction. Apres 60 minutes d'ischemie, 28% de l'inuline n'est pas recuperee dans les urines des deux reins; apres 25 minutes d'ischemie cette valeur est de 12%. Les trois quarts environ de l'inuline manquante sont trouves dans le rein lui-meme. La recuperation de rinuline est pratiquement totale chez les animaux controles ou apres 15 minutes d'ischemie. Des fragments boursouffles de bordure en brosse sont encastres dans 75% des PST apres 60 minutes d'ischemie alors que cet aspect est beaucoup plus rare apres 25 minutes d'ischemie. Nous concluons que l'allongement de la duree de l'ischemie renale determine une augmentation de la fuite des grosses molecules a travers les cellules lesees de la paroi tubulaire. Apres 60 minutes d'ischemie, la plupart des PST sont remplis de fragments encastres de bordure en brosse, ce qui determine l'obstruction.