Zager R A, Alpers C E
Department of Medicine, University of Washington, Seattle.
Lab Invest. 1989 Sep;61(3):290-4.
Ischemic acute renal failure is principally a disease of the elderly, but the effect of aging on renal susceptibility to ischemic damage has not been defined. To address this issue, adolescent (3-4 months), mature (12-13 months), and aged (24-25 months) rats underwent base-line renal functional assessments, and then they were subjected to a standardized ischemic event (37-minute, bilateral renal artery occlusion). The loss of renal function [assessed by azotemia and creatinine clearance, (Ccr)] and the severity of tubular damage (necrosis, casts) were determined 24 hours later. Base-line functional assessments indicated no significant differences in Ccr/100 gm body weight between the groups, but urinary protein excretion increased with age (p less than 0.001). In response to renal artery occlusion, the adolescent, mature, and aged rats lost 59 +/- 4, 82 +/- 4, and 94 +/- 1% of their base-line Ccr (p less than 0.01), respectively. Among the proteinuric rats, no correlation was noted between percent loss Ccr and urinary protein excretion. Despite the large differences in postischemic renal function, the extent of tubular morphologic damage did not differ among the groups. The percent loss Ccr did not correlate with necrosis (r = -0.02) or casts (r = 0.07). Although focal glomerulosclerosis and mild tubular atrophy were noted in the aged kidneys these lesions were minimal to absent in the mature rats. We conclude that aging increases susceptibility to severe ischemic acute renal failure in the rat, an effect that is apparent even during a transition from the adolescent to the mature state. This finding cannot be simply ascribed to increasing proteinuria, a loss of renal functional reserve, or to increased tubular morphologic damage. The data are most consistent with the view that underlying age-related glomerular/hemodynamic changes lead to an exaggerated functional decline in response to ischemic renal injury.
缺血性急性肾衰竭主要是一种老年疾病，但衰老对肾脏缺血性损伤易感性的影响尚未明确。为解决这一问题，对青春期（3 - 4个月）、成年（12 - 13个月）和老年（24 - 25个月）大鼠进行基线肾功能评估，然后使其经历标准化缺血事件（37分钟双侧肾动脉闭塞）。24小时后测定肾功能丧失情况[通过氮质血症和肌酐清除率（Ccr）评估]以及肾小管损伤的严重程度（坏死、管型）。基线功能评估表明，各组间每100克体重的Ccr无显著差异，但尿蛋白排泄量随年龄增加（p < 0.001）。肾动脉闭塞后，青春期、成年和老年大鼠分别丧失其基线Ccr的59±4%、82±4%和94±1%（p < 0.01）。在蛋白尿大鼠中，Ccr丧失百分比与尿蛋白排泄量之间未发现相关性。尽管缺血后肾功能存在巨大差异，但各组间肾小管形态学损伤程度并无不同。Ccr丧失百分比与坏死（r = -0.02）或管型（r = 0.07）均无相关性。虽然在老年肾脏中观察到局灶性肾小球硬化和轻度肾小管萎缩，但这些病变在成年大鼠中极少或不存在。我们得出结论，衰老增加了大鼠对严重缺血性急性肾衰竭的易感性，即使在从青春期到成年期的过渡阶段这种影响也很明显。这一发现不能简单地归因于蛋白尿增加、肾功能储备丧失或肾小管形态学损伤增加。这些数据与以下观点最为一致，即与年龄相关的潜在肾小球/血流动力学变化导致对缺血性肾损伤的功能下降加剧。
