Müller-Krebs S, Kihm L P, Zeier B, Gross M L, Deppisch R, Wieslander A, Henle T, Penndorf I, Oh J, Reiser J, Nawroth P P, Zeier M, Schwenger V
Medical University of Heidelberg, Heidelberg, Germany.
Eur J Clin Invest. 2008 May;38(5):296-305. doi: 10.1111/j.1365-2362.2008.01945.x. Epub 2008 Mar 16.
In peritoneal dialysis (PD) residual renal function contributes to improved patient survival and quality of life. Glucose degradation products (GDP) generated by heat sterilization of PD fluids do not only impair the peritoneal membrane, but also appear in the systemic circulation with the potential for organ toxicity. Here we show that in a rat model of advanced renal failure, GDP affect the structure and function of the remnant kidney.
Sprague-Dawley rats were randomly assigned to a two stage subtotal nephrectomy (SNX) or sham operation and were left untreated for 3 weeks. The SNX + GDP group continuously received chemically defined GDP intravenously for 4 weeks; the SNX and the sham-operated rats remained without GDP. The complete follow-up for all groups was 7 weeks postoperatively. We analysed renal damage using urinary albumin excretion as well as a semiquantitative score for glomerulosclerosis and tubulointerstitial damage, as well as for immunohistochemical analyses.
The SNX + GDP rats developed significantly more albuminuria and showed a significantly higher score of glomerulosclerosis index (GSI) and tubulointerstitial damage index (TII) as compared to SNX or control rats. In the SNX + GDP group the expression of carboxymethyllysine and methylglyoxal was significantly higher in the tubulointerstitium and the glomeruli compared to the SNX rats. Caspase 3 staining and TUNEL assay were more pronounced in the tubulointerstitium and the glomeruli of the SNX + GDP group. In SNX + GDP animals, the expression of the slit diaphragm protein nephrin, was significantly lower compared to SNX or control animals.
In summary, our data suggests that GDP can significantly advance chronic kidney disease and argues that PD solutions containing high GDP might deteriorate residual renal function in PD.
在腹膜透析（PD）中，残余肾功能有助于提高患者生存率和生活质量。腹膜透析液热灭菌产生的葡萄糖降解产物（GDP）不仅会损害腹膜，还会进入体循环，可能导致器官毒性。在此我们表明，在晚期肾衰竭大鼠模型中，GDP会影响残余肾脏的结构和功能。
将Sprague-Dawley大鼠随机分为两组，分别接受两阶段次全肾切除术（SNX）或假手术，术后3周不进行任何处理。SNX + GDP组连续4周静脉输注化学定义的GDP；SNX组和假手术组大鼠不接受GDP。所有组的完整随访期为术后7周。我们通过尿白蛋白排泄、肾小球硬化和肾小管间质损伤的半定量评分以及免疫组织化学分析来评估肾损伤。
与SNX组或对照组大鼠相比，SNX + GDP组大鼠出现明显更多的蛋白尿，肾小球硬化指数（GSI）和肾小管间质损伤指数（TII）得分显著更高。与SNX组相比，SNX + GDP组肾小管间质和肾小球中羧甲基赖氨酸和甲基乙二醛的表达明显更高。SNX + GDP组肾小管间质和肾小球中的半胱天冬酶3染色和TUNEL检测更为明显。与SNX组或对照组动物相比，SNX + GDP组动物中裂孔隔膜蛋白nephrin的表达明显降低。
总之，我们的数据表明GDP可显著促进慢性肾病发展，并表明含有高GDP的腹膜透析液可能会使腹膜透析患者的残余肾功能恶化。
