A search for nephrotoxic factors within the uremic milieu

The purpose of this study was to ascertain whether selected components of the uremic milieu adversely affected glomerular filtration rate (GFR), the glomerular protein filtration barrier, or the integrity of the proximal renal tubular brush border membrane. To achieve these goals, GFR and the excretion rates of albumin and of brush border derived-renal tubular epithelial antigens (RTE) were measured in normal rats and in rats with experimental nephropathies before and after the intravenous infusion of concentrated urine. This experimental protocol uniformly produced severe biochemical manifestations of uremia (for example 10-50-fold increases in BUN and creatinine, hyperphosphatemia, hyperkalemia, metabolic acidosis). However, despite these perturbations, GFR, albuminuria, and RTE excretion remained constant. To assess the influence of uremic hormonal derangements on renal function, GFR, albuminuria, and RTE excretion were measured in normal rats before and after inducing acute serum elevations of seven hormones whose concentrations are known to be increased in uremia (parathyroid hormone, growth hormone, insulin, glucagon, gastrin, prolactin, gastric inhibitory peptide). Again, GFR, albuminuria, and RTE excretion were not adversely affected. These results suggest that glomerular capillary function and proximal tubular brush border membranes are acutely resistant to many of the solute and hormonal derangements which are characteristic of uremia.