Acute-on-chronic renal failure in the rat: Functional compensation and hypoxia tolerance
Acute-on-chronic renal failure in the rat: Functional compensation and hypoxia tolerance
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DOI：
10.1159/000091783
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发表时间：
2006-01-01
影响因子：
4.2
通讯作者：
Heyman, SN
中科院分区：
文献类型：
--
作者：
Goldfarb, M;Rosenberger, C;Heyman, SN
背景我们假设慢性肾实质疾病可能易诱发急性肾功能衰竭（ARF），促进缺氧性肾小管损伤的诱导。方法：采用假手术（对照组）或双侧肾动脉阻断50 min [缺血再灌注（IR）]诱导大鼠慢性肾实质损伤。一个月或三个月后，两组都进行了ARF协议，包括放射性造影剂和前列腺素和一氧化氮合成的抑制。24 h后测定肾功能和形态学。结果如下：IR组的慢性肾小管间质改变（纤维化、萎缩和肥大）与基线肾小管功能相关，但肾小球功能得以保留。在IR组中，ARF方案后的功能恶化仅略微更明显，并且髓质急性肾小管坏死（ATN）的程度不受先前IR的影响。肾小管坏死和慢性肾小管间质变化的程度独立预测肾功能的急性下降。IR肾脏的免疫染色显示髓质pO（2）极低（通过pimonidazole加合物测定），局部缺氧细胞反应（缺氧诱导因子）和内皮素B受体上调。结论：代偿性变化导致IR后1个月和3个月血浆肌酐正常，尽管肾小管功能下降。既存肾脏疾病仅轻微易患ARF，ATN的程度并不显著增强。这些发现说明了慢性和急性肾损伤和功能障碍之间复杂的相互作用，并平行的困难，他们的评估在临床实践中。慢性缺氧的适应性细胞反应与脑实质损伤和需氧量降低可能减轻急性缺氧损伤。版权所有（C）2006 S. Karger AG，巴塞尔。
Background. We hypothesized that chronic renal parenchymal disease may predispose to acute renal failure (ARF), facilitating the induction of hypoxic medullary tubular injury. Methods:To induce chronic renal parenchymal injury, rats underwent sham operation (control) or bilateral 50-min clamping of the renal artery [ischemia-reperfusion (IR)]. One or 3 months later, both groups were subjected to an ARF protocol, consisting of radio-contrast and the inhibition of prostaglandin and nitric oxide synthesis. Renal function and morphology were determined 24 h later. Results: Chronic tubulointerstitial changes (fibrosis, atrophy and hypertrophy) in the IR group correlated with baseline tubular function, but glomerular function was preserved. Functional deterioration after the ARF protocol was only marginally more pronounced in the IR group, and the degree of medullary acute tubular necrosis (ATN) was unaffected by prior IR. The extent of both tubular necrosis and chronic tubulointerstitial changes independently predicted the acute decline in renal function. Immunostaining of IR kidneys disclosed critically low medullary pO(2) (determined by pimonidazole adducts), regional hypoxic cell response (hypoxia-inducible factors) and upregulation of endothelin-B receptors. Conclusions: Compensatory changes result in normal plasma creatinine 1 and 3 months after IR, despite diminished tubular function. Preexisting renal disease only marginally predisposes to ARF, and the extent of ATN is not significantly enhanced. These findings illustrate the complex interaction between chronic and acute renal injury and dysfunction and parallel the difficulty of their assessment in the clinical practice. Adaptive cellular responses to chronic hypoxia in conjunction with parenchymal loss and decreased oxygen demand might alleviate acute hypoxic injury. Copyright (C) 2006 S. Karger AG, Basel.