Zager R A, Johannes G, Tuttle S E, Sharma H M
J Lab Clin Med. 1983 Jan;101(1):130-40.
Previous clinical and experimental data suggest that a limited number of AAs with particular molecular characteristics can adversely affect renal function. The present investigation was conducted to better define the scope and the molecular basis of this nephrotoxicity. Sprague-Dawley rats (N = 31) undergoing a solute diuresis were subjected to 80 min infusions (125 mumol/kg/min) of cationic AAs (lysine, arginine), anionic AAs (glutamic acid, aspartic acid), or neutral AAs (alanine, glycine). Rats infused for 80 min with equimolar amounts of urea or dextrose served as controls (N = 8). GFR (Cioth) were measured 40 min before, during, and 140 min after these infusions. Albumin excretion rates were determined by radioimmunoassay. All AA infusates induced significant (p less than 0.001) reductions in GFR compared to the control infusates (cationic AAs: 62% +/- 4; anionic AAs: 57% +/- 5; neutral AAs: 33% +/- 1; controls: 8% +/- 4) (X +/- S.E.M.). However, only cationic AAs induced a significant increase in albumin excretion (360% +/- 72; p less than 0.001). AA-treated rats had histologic changes with mild tubular injury compared to control rats. These data indicate the following. (1) AAs have in common a nephrotoxic potential. (2) This nephrotoxicity arises, in part, from the nonvariable portion of AA molecules since glycine, which has no variable (R) group, induced a significant reduction in GFR (32% +/- 1). (3) The ability of AAs to decrease GFR is enhanced by certain R groups. However, R group charge is not a critical factor in producing this response. (4) AA-induced increments in albumin excretion and reductions in GFR must arise via independent mechanisms. Since AA infusions are commonly used in patients with ARF the possibility that such therapy might have a deleterious effect on renal function and on the subsequent recovery from ARF should be entertained.
先前的临床和实验数据表明，数量有限的具有特定分子特征的氨基酸可能会对肾功能产生不利影响。本研究旨在更好地界定这种肾毒性的范围和分子基础。对处于溶质利尿状态的斯普拉格-道利大鼠（N = 31）进行80分钟的阳离子氨基酸（赖氨酸、精氨酸）、阴离子氨基酸（谷氨酸、天冬氨酸）或中性氨基酸（丙氨酸、甘氨酸）输注（125 μmol/kg/分钟）。输注等摩尔量尿素或葡萄糖80分钟的大鼠作为对照（N = 第八条）。在这些输注前40分钟、输注期间和输注后140分钟测量肾小球滤过率（Cioth）。通过放射免疫测定法测定白蛋白排泄率。与对照输注相比，所有氨基酸输注液均导致肾小球滤过率显著降低（p <0.001）（阳离子氨基酸：62%±4；阴离子氨基酸：57%±5；中性氨基酸：33%±1；对照：8%±4）（X±标准误）。然而，只有阳离子氨基酸导致白蛋白排泄显著增加（360%±72；p <0.001）。与对照大鼠相比，氨基酸处理的大鼠出现了伴有轻度肾小管损伤的组织学变化。这些数据表明如下几点。（1）氨基酸具有共同的肾毒性潜力。（2）这种肾毒性部分源于氨基酸分子的不变部分，因为没有可变（R）基团的甘氨酸导致肾小球滤过率显著降低（32%±1）。（3）某些R基团增强了氨基酸降低肾小球滤过率的能力。然而，R基团电荷不是产生这种反应的关键因素。（4）氨基酸诱导的白蛋白排泄增加和肾小球滤过率降低必定通过独立机制发生。由于氨基酸输注常用于急性肾衰竭患者中应考虑到这种治疗可能对肾功能以及随后从急性肾衰竭中恢复产生有害影响的可能性。
