A new quantitative procedure for proteinuria

Abnormalities of tubular cells were treated by administration of nephrotoxin and studied by specialized gel filtration methods to discern early quantitative and qualitative changes in proteinuria. Dogs given nephrotoxic doses of Diglycoaldehyde, alpha-(hydroxymethyl)-alpha1-(6-hydroxy-9H-purine-9-yl) 60 mg per kg per day intravenously, for 3 days showed a marked reduction in effective renal plasma flow from 264.91 +/- 90.05 ml per min to 125.0 +/- 19.0 ml per min as measured by 131I sodium iodohippurate, and corresponding decrease in total renal perfusion by 131I xenon wash-out from 222.2 +/- 8.6 to 124.0 +/- 28.38. However, after treating four dogs with 20 mg per kg, an increase in effective renal plasma flow was obtained. Histologic changes of glomerular and tubular damage were demonstrated. Urine from this same series of animals was examined on a daily basis by sucrose-acrylamide gradient gel centrifugation together with ultraviolet scanning. Specific patterns were also obtained using dialyzed urine which eliminated molecules greater than 3500 mol wt. The ultraviolet pattern data were digitized and analyzed on computers to augment pattern recognition. These techniques indicted that molecules (3500 mol wt or less) were excreted in response to a known nephrotoxic agent, establishing early distinctive changes in tubular cells and also relating to alteration in renal function.