Effect of urinary pH and diatrizoate on Bence Jones protein nephrotoxicity in the rat

Both low urinary pH and radiocontrast agents may intensify myeloma nephrotoxicity. To study the effects of these factors, we determined inulin clearances (CIn) before and after infusions of human Bence Jones protein (BJP) in male Sprague-Dawley rats in a dose previously shown to be nephrotoxic. Rats that drank 0.15 M NaHCO3 for 48 hr before study had no change in CIn (+3 +/- 20%) after BJP unlike those that drank 0.15 M NH4Cl (-33 +/- 14%, P less than 0.05); urinary pH differed (7.6 +/- 0.1 vs. 6.2 +/- 0.1, P less than 0.05), but urinary flow rates did not. The acidifying regimen was used in all subsequent groups. Infusion of diatrizoate (DTZ) after BJP produced a further decrease in CIn (-85 +/- 8%, P less than 0.05). In contrast, infusion of albumin, which raised plasma protein concentration to that seen in BJP-infused rats, did not change CIn (+39 +/- 17%). Infusion of beta-lactoglobulin also led to a greater decrease in CIn after DTZ (-35 +/- 9 vs. -67 +/- 8%, P less than 0.05), but myoglobin did not (-58 +/- 7 vs. -54 +/- 12%). Urinary pH and flow rate did not differ between any DTZ-infused group and its appropriate control. These data suggest that aciduria independent of urinary flow rate increases the nephrotoxicity of BJP. In this setting, DTZ further intensifies the nephrotoxicity of BJP as well as some but not all filterable proteins.