Glomerular Ultrafiltration Coefficient after Ischemic Renal Injury in Dogs

Micropuncture studies of acute renal failure after ischemic renal injury suggest that glomerular ultrafiltration coefficient may remain normal in the period immediately after ischemia and decline significantly during the following 18–24 hours. The present series of in vitro experiments was designed to evaluate glomerular ultrafiltration coefficient and glomerular onco- metric and rheological properties in ischemic acute renal failure in dogs. To obtain glomeruli prior to ischemia, a right nephrectomy was performed and glomeruli were isolated for studies of filtration and cell and extracellular spaces. The left renal pedicle then was occluded for 90 minutes; glomeruli isolated from biopsies of this kidney were studied at intervals up to 48 hours after ischemia. Glomeruli were isolated by sieving renal cortical fragments, and filtration was induced by an oncouc gradient. The glomerular ultrafiltration coefficient remained near control levels for the first hour after ischemia, but declined significantly at 24 and 48 hours. Specifically, glomerular ultrafiltration coefficient of glomeruli isolated from normal kidneys was 16.5 ± 0.9 nl/min per mm Hg(n = 15). Immediately following ischemia, glomerular ultrafiltration coefficient remained essentially unchanged (15.9 ±1. 1 nl/min per mm Hg, n = 4). At 1 hour, there was a small decrease in glomerular ultrafiltration coefficient (14.4 ± 1.3 nl/min per mm Hg, n = 4). At 24 hours, glomerular ultrafiltration coefficient was significantly decreased (9.8 ± 0.5 nl/min per mm Hg, n = 9, P < 0.01) and remained at that level at 48 hours (9.5 ± 0.5 nl/min per mm Hg, n = 8, P < 0.001). In experimental glomeruli, the oncometric response was diminished and erythrocyte movement along glomerular capillaries was impaired. Total water and inulin spaces were measured in glomeruli from control and 48-hour postischemic periods, and glomerular morphology was studied by transmission and scanning electron microscopy at the same time. Intracellular water comprised a significantly larger portion of total glomerular water 48 hours after ischemia than during the control period. Concurrent morphological changes included a decrease in the diameter of endothelial fenestrae and widening of epithelial foot processes. These results are consistent with the view that one or more nonglomerular factors are responsible for profound oliguria during the early phase of acute renal failure after ischemia. However, reduction of glomerular ultrafiltration coefficient, probably secondary to altered glomerular cellular characteristics, may be an important determinant to decreased glomerular filtration rate in established acute renal failure.