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Nephrology Dialysis Transplantation, Vol 12, Issue 6 1116-1121, Copyright © 1997 by Oxford University Press

ORIGINAL ARTICLES

D-Penicillamine reduces renal injury in the remnant model of chronic renal failure in the rat

D Throssell, J Brown, P Furness, G Rutty, J Walls and K Harris
Departments of Nephrology and Pathology, Leicester General Hospital, Leicester, UK; Corresponding author address: Sheffield Kidney Institute, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK

Background. Glomerulosclerosis and interstitial fibrosis, which are cardinal features of the end-stage kidney, result from accumulation of extracellular matrix proteins, particularly collagen, in the glomerular mesangium and renal interstitium. This study examined the effect of D-penicillamine (DPC), which inhibits collage deposition, on disease progression in the remnant kidney. Methods. Two groups of 10 rats underwent two-thirds nephrectomy and were pair-fed 20% casein past (Gp 1) or the same paste supplemented with 90 mg/kg body wt per day of DPC (Gp 2). Two further groups of five non-nephrectomized animals also received 20% casein paste either alone (Gp 3) or supplemented with DPC (Gp 4). In a further experiment, systolic blood pressure was compared at 1 and 4 weeks after nephrectomy in eight DPC-treated remnants and eight untreated controls. Results. Gp 2 developed significantly less proteinuria than Gp 1 (41±9 vs 142±33 mg/24 h at 6 weeks, P<0.005; 136±36 vs 282±59 mg/24 h at 12 weeks, P<0.05). At sacrifice after 12 weeks, glomerular filtration rates were higher (1.34±0.08 vs 1.07±0.1 ml/min, P<0.05), kidney total collagen content was lower (14.9±1.5 vs 26.9±5.4 mg/kidney, P0.05) and glomerular abnormalities, interstitial fibrosis and lymphocytic infiltration were less marked in Gp 2 compared with Gp 1. DPC had no effect on protein excretion, total kidney collagen or GFR in non-nephrectomized rats, and did not influence the early rise in blood pressure seen after two-thirds nephrectomy. Conclusions. These findings demonstrate that DPC reduces renal injury in the remnant kidney, and raise the possibility of a therapeutic role for DPC in the treatment of patients with chronic renal failure. Keywords: collagen; D-penicillamine; fibrosis; remnant kidney
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