Holland M D, Galla J H, Sanders P W, Luke R G
Kidney Int. 1985 Jan;27(1):46-50. doi: 10.1038/ki.1985.8.
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.
低尿pH值和放射性造影剂均可加重骨髓瘤肾毒性。为研究这些因素的影响，我们以先前已证实具有肾毒性的剂量，在雄性Sprague-Dawley大鼠中输注人本周氏蛋白（BJP）前后测定菊粉清除率（CIn）。在研究前饮用0.15 M NaHCO₃ 48小时的大鼠，输注BJP后CIn无变化（+3±20%），而饮用0.15 M NH₄Cl的大鼠CIn下降（-33±14%，P<0.05）；尿pH值不同（7.6±0.1对6.2±0.1，P<0.05），但尿流率无差异。所有后续组均采用酸化方案。BJP后输注泛影酸盐（DTZ）使CIn进一步降低（-85±8%，P<0.05）。相比之下，输注白蛋白使血浆蛋白浓度升至输注BJP大鼠的水平，但CIn无变化（+39±17%）。输注β-乳球蛋白也导致DTZ后CIn下降幅度更大（-35±9对-67±8%，P<0.05），但肌红蛋白无此现象（-58±7对-54±12%）。任何输注DTZ组与其相应对照组之间的尿pH值和尿流率均无差异。这些数据表明，与尿流率无关的酸性尿会增加BJP的肾毒性。在此情况下，DTZ会进一步加重BJP以及部分但并非全部可滤过蛋白的肾毒性。
