HYPERHOMOCYSTEINEMIA EXACERBATES THE NEPHRON INJURIES INDUCED BY EXPERIMENTAL KIDNEY FAILURE

THE AIM of the investigation was to evaluate a possible impact of homocysteine (HCy) on the glomerular and proximal tubule cell injury in the remnant kidney model (RKM). MATERIAL AND METHODS. An experimental group of adult male albino Wistar rats underwent subtotal nephrectomy followed by daily administration of HCy (i.m., 13.4 mg/kg) for three weeks (n=11). Nephrectomized rats not given HCy were used as a control group (n=11). Routine blood and urine functional tests as well as light and electron microscopic examinations of the kidney samples were used to compare urine albumincreatinine ratio (ACR), creatinine clearance (Ccr) and cell alterations in RKM alone and those with a combination of RKM and superimposed hyperhomocysteinemia. RESULTS. Total plasma HCy was 5.0±0.7 and 7.7±1.5 in control and experimental animals respectively (p< 0.005). In the experimental group an increased logACR per 100 g of body mass (2.12±0.52 vs 1.43±0.32 mg/g, p<0.025) and plasma creatinine concentration (79.0±13.9 vs 56.3±8.0, p< 0.001) and decreased Ccr (0.20±0.7 vs 0.46±0.08 ml/min, p<0.005) and Ucr/Pcr (53.2±25.9 vs 123±25.7, p<0.005) were observed as compared to the control group. Moderate mesangial cell proliferation and local leukocyte adhesion to the endothelial lining in the glomeruli, with a pronounced increase of the amount of endocytosislabeling structures, large apical vacuoles included, in the proximal tubule cells, were registered in the kidney parenchyma of the RKM rats. Administration of HCy apparently aggravated the above mentioned alterations in both nephron compartments and also resulted in fibrin deposition within the glomerular capillaries and extensive disorganization of the basal cytoplasm in the proximal tubule cells. CONCLUSION. Both light and electron microscopic data reinforced by the appropriate biochemical findings are considered as a direct evidence of the additional deleterious effects of HCy on the major cell populations of the nephron under conditions of experimental renal failure.

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