Nephrol Dial Transplant (2002) 17: 2132-2137
© 2002 European Renal Association-European Dialysis and Transplant Association
22-Oxacalcitriol prevents progressive glomerulosclerosis without adversely affecting calcium and phosphorus metabolism in subtotally nephrectomized rats
1 Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, Shizuoka, 2 Division of Artificial Kidneys, Faculty of Medicine, Kyoto University, Kyoto and 3 Department of Laboratory Medicine, School of Medicine, University of Tokushima, Tokushima, Japan
Background. 22-Oxacalcitriol (OCT), an analogue of vitamin D, has been shown to inhibit cell proliferation in cultured mesangial cells. OCT also prevented albuminuria and glomerular injury in an acute model of anti-Thy1 glomerulonephritis. However, potential side effects, including calcaemic actions and tubular dysfunction, of chronic OCT treatment remain unclear. In the present study, we evaluated the effect of OCT in a chronic model of progressive glomerulosclerosis in subtotally nephrectomized (SNX) rats.
Methods. At one week after subtotal nephrectomy, SNX rats were divided into 3 groups having equivalent serum creatinine levels and body weight. OCT (0.08 or 0.4 µg/kg body weight) was administered intravenously three times per week for 8 weeks to SNX rats. We evaluated effects of OCT on renal function during treatment and on morphologic parameters in glomeruli at 8 weeks. We additionally measured calcium and phosphate levels in serum and urine, and tubular dysfunction markers, including ß2-microgloblin (ß2m) and N-acetyl-ß-D-glycosaminidase (NAG) levels in urine.
Results. OCT treatment significantly suppressed urinary albumin excretion, prevented increases in serum creatinine and serum urea nitrogen, and inhibited glomerular cell number, glomerulosclerosis ratio and glomerular volume in SNX rats at 8 weeks. At that time, OCT-treated groups did not show hypercalcaemia, hypercalciuria or hyperphosphaturia. Furthermore, OCT treatment did not affect ß2m or NAG levels in urine, and did not induce histological changes in tubular or interstitial regions.
Conclusions. These findings suggest that OCT may provide a clinically useful agent for preventing the progression of glomerulosclerosis without adversely affecting calcium and phosphorus metabolism or causing subsequent tubular dysfunction.
Keywords: glomerulosclerosis; hypercalcaemia; hyperphosphataemia; 22-oxacalcitriol (OCT); tubular dysfunction
Correspondence and offprint requests to: Michinori Hirata, Pharmaceutical Research Laboratory II, Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd, 135 Komakado, 1 chome, Gotemba-shi, Shizuoka 412-8513, Japan. E-mail:hiratamcn{at}chugai-pharm.co.jp
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