HDCN Abstract:  ASN Annual Meeting -- San Francisco  

Mueller-Krebs S, Kihm LP, Zeier B, et al.

Renal Toxicity of Glucose Degradation Products in Peritoneal Dialysis.

ASN Annual Meeting -- San Francisco
J Am Soc Nephrol (Nov) 18:690A 2007

Purpose: In peritoneal dialysis residual renal function contributes to improved patient survival and quality of life. Glucose degradation products (GDP) impair not only the peritoneal membrane, they appear in the systemic circulation with potential organ toxicity. In subtotally nephrectomized (SNX) rats, we examined whether GDP affects the structure and function of the remnant kidney.

Methods: Sprague-Dawley (SD) rats were randomly assigned to a two-stage SNX or sham operation and were left untreated for 3 weeks. SNX+GDP group received chemically defined GDP by an osmotic mini-pump intravenously for 4 weeks; the SNX and the sham operated groups remained without GDP. The complete follow-up for all groups was 7 weeks post- operatively.

Results: The SNX+GDP rats developed significantly more albuminuria (12.3 4.96 mg/24 h vs. SNX 5.68 2.77 mg/24 h; p 0.05) and showed a significantly higher index of glomerulosclerosis (2.18 0.33 vs. 1.82 0.23; p 0.01) and tubulointerstitial damage (2.17 0.29 vs. 1.78 0.22; p 0.01). In SNX+GDP expression of carboxymethyllysin and methylglyoxal was significantly higher in the tubulointerstitium and the glomeruli compared to the SNX rats. Caspase 3 and TUNEL assay were more pronounced in the tubulointerstitial space and the glomeruli of the SNX+GDP. In SNX+GDP animals podocyte damage was significantly higher compared to SNX and sham operated animals. Blood pressure was similar in SNX+GDP (134 8.63) versus SNX (135 9.25; p=ns).

Conclusion: In subtotally nephrectomized rats, administration of GDP increased albuminuria, indices of glomerular and tubulointerstitial damage significantly, specifically with a rarefication and perturbation of podocytes. It is likely that GDP-free PD solutions maintain and stabilize residual renal function in PD.

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