Glomerular epithelial cell changes in early postischemic acute renal failure in rabbits and man.

Spreading and flattening of glomerular podocyte cell bodies and major processes and an apparent lack of foot processes were observed by scanning electron microscopy in a reversible pedicle-clamping model of acute renal failure in ADH-treated rabbits and in biopsy specimens taken 1 hour after transplantation from patients who later showed clinical signs of "acute tubular necrosis." Glomerular changes were quantified by morphometry in A) normal rabbit kidneys, B) rabbit kidneys obtained 2 hours after 1 hour of left pedicle clamping and right nephrectomy, C) kidneys similar to Group B except that the animals were treated with an agent that reliably lessens the eventual severity of renal failure (clonidine, 30 microgram/kg given intravenously 1/2 hour before unclamping), D) 1-hour-posttransplantation biopsy specimens from human kidneys that functioned well after transplantation (recipient serum creatinine less than 2.5 mg/dl on Day 3), and E) 1-hour-posttransplant biopsy specimens from kidneys that later manifested posttransplantation ischemic acute renal failure (recipient serum creatinine greater than or equal to 2.5 mg/dl on Day 3). The fraction of glomerular capillary surface covered only by podocyte processes smaller than 1 mu (and not by cell bodies and wider processes) was .65 +/- .02 (SEM) in A; .48 +/- .03 in B; .64 +/-.03 in C; .57 +/- .01 in D; and .38 +/- .04 in E (A vs B, P less than .01; B vs C, P less than .02; D vs E, P less than .01). In Groups D and E there was a significant negative correlation between the fraction of glomerular capillary surface covered only by podocyte processes less than 1 mu in width and serum creatinine on the third posttransplantation day (r = --.86, P less than .01 by the Spearman rank test). It is concluded that podocyte changes are seen by scanning electron microscopy early in clinical and experimental postischemic acute renal failure and are more pronounced in those groups that eventually develop more severe renal failure. It is unclear whether these changes reflect a decrease in glomerular hydraulic permeability or an increase in glomerular permeability to protein.