Institute of Pharmacology & Experimental Therapeutics, IBILI, Medicine Faculty, Coimbra University, Coimbra, Portugal.
Ren Fail. 2009;31(9):833-42. doi: 10.3109/08860220903151435.
The pathophysiological modifications underlying chronic renal failure seems to be dependent on the insufficiency degree, which will determine the moment to start therapy. As there is yet limited information about animal models of moderate chronic renal failure, we intended to perform a complete characterization of the hematological and cardio-renal alterations induced by partial nephrectomy. Blood samples from control and chronic renal failure rats were collected at 0, 3, 9, and 15 weeks in order to evaluate renal function, hematological parameters, iron metabolism, blood lipids, peripheral sympathetic nervous system, and inflammatory and redox status markers. BP, tissues trophy indexes, and kidney histomorphology were also assessed. Our data are consistent with a sustained moderate degree of chronic renal failure with a quickly compensated modest anaemia, though presenting iron metabolism disturbances. Despite the reasonable degree of functionality of the remnant kidney, as suggested by the anaemia correction and by the kidney hypertrophy and moderate lesions, several important cardiovascular modifications were developed. Our model presented hypertension, dyslipidemia, erythropoietic disturbances, sympathetic activation, and oxidative stress. This model might be a good tool to study the cellular/molecular mechanisms underlying moderate stages of chronic renal failure and to evaluate the therapeutic efficacy for prevention and treatment/correction of cardio-renal anaemia syndromes and complications in early stages.
慢性肾衰竭的病理生理改变似乎取决于其严重程度,这将决定开始治疗的时机。由于关于中度慢性肾衰竭动物模型的信息有限,我们旨在对部分肾切除术引起的血液学和心肾改变进行全面描述。分别在第 0、3、9 和 15 周时采集对照组和慢性肾衰竭大鼠的血液样本,以评估肾功能、血液参数、铁代谢、血脂、外周交感神经系统以及炎症和氧化还原状态标志物。还评估了血压、组织营养指数和肾脏组织学。我们的数据与持续中度慢性肾衰竭一致,伴有代偿性轻度贫血,尽管存在铁代谢紊乱。尽管剩余肾脏的功能保持在合理的水平,如贫血纠正、肾脏肥大和中度病变所表明的那样,还是出现了几个重要的心血管改变。我们的模型表现出高血压、血脂异常、红细胞生成障碍、交感神经激活和氧化应激。该模型可能是研究慢性肾衰竭中度阶段细胞/分子机制以及评估预防和治疗/纠正早期心肾贫血综合征和并发症的治疗效果的良好工具。