GLOMERULAR EPITHELIAL-CELL CHANGES IN EARLY POST-ISCHEMIC ACUTE-RENAL-FAILURE IN RABBITS AND MAN

  • 1 January 1981
    • journal article
    • research article
    • Vol. 103  (2) , 163-173
Abstract
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 h after transplantation from patients who later showed clinical signs of acute tubular necrosis. Glomerular changes were quantified by morphometry in normal rabbit kidneys (group A), rabbit kidneys obtained 2 h after 1 h of left pedicle clamping and right nephrectomy (group B), 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 .mu.g/kg given i.v. 1/2 h before unclamping) (group C), 1 h posttransplantation biopsy specimens from human kidneys that functioned well after transplantation (recipient serum creatinine < 2.5 mg/dl on Day 3) (group D), and 1 h posttransplant biopsy specimens from kidneys that later manifested posttransplantation ischemic acute renal failure (recipient serum creatinine .gtoreq. 2.5 mg/dl on Day 3) (group E). The fraction of glomerular capillary surface covered only by podocyte processes smaller than 1 .mu. (and not by cell bodies and wider processes) was 0.65 .+-. 0.02 (SEM) in A; 0.48 .+-. 0.03 in B; 0.64 .+-. 0.03 in C; 0.57 .+-. 0.01 in D; and 0.38 .+-. 0.04 in E (A vs. B, P < 0.01; B vs. C, P < 0.02; D vs. E, P < 0.01). In Groups D and E there was a significant negative correlation between the fraction of glomerular capillary surface covered only by podocyte processes < 1 .mu. in width and serum creatinine on the third posttransplantation day (r = -0.86, P < 0.01 by the Spearman rank test). Apparently, podocyte changes are seen by scanning electron microscopy early in clinical and experimental postischemic acute renal failure and are more pronounced in 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.