Neutrophil-mediated post-ischemic tubular leakage in the rat kidney.

Neutropenia was induced in male Sprague-Dawley rats by administration of antineutrophil serum (ANS). A control group received an equal volume of inactive serum. After 45 minutes of unilateral complete renal ischemia the renal blood flow (RBF) was measured by an electromagnetic flow meter. The net filtration force (NFF) in glomerular capillaries, single nephron filtration rate (SNGFR) and frequency of tubular obstructions were estimated by a micropuncture technique. Tubular leakage was measured from the fractional recovery in the normal contralateral kidney of 3H- or 14C-inulin injected into surface proximal and distal tubules of the post-ischemic kidney. Neither ANS nor inactive serum had any influence on inulin clearance (CIn) in the normal kidney. In the post-ischemic kidney, CIn was four times higher in ANS-treated than in control animals. There was no difference in RBF, NFF, SNGFR or the frequency of tubular obstructions between neutrophil-depleted and control animals. The transtubular leakage of inulin injected into proximal tubules was substantially less in the ANS-treated than in the control group (11.3 +/- 1.5% vs. 35.1 +/- 6.5%; P less than 0.01). But distal tubular leakage was equal in the two groups. The control group showed isothenuria (350 +/- 29 mOsm.kg-1), while ANS-treated animals produced hyperosmolar urine (555 +/- 60 mOsm.kg-1; P less than 0.05). It is concluded that neutrophil granulocytes mediate post-ischemic tubular leakage, which contributes to the depression in renal clearance parameters and the inability to produce hyperosmolar urine.