D-PENICILLAMINE REDUCES RENAL INJURY IN THE REMNANT MODEL OF CHRONIC-RENAL-FAILURE IN THE RAT

Background. Glomerulosclerosis and interstitial fibrosis, which are ca rdinal features of the end-stage kidney, result form accumulation of e xtracellular matrix proteins, particularly collagen, in the glomerular mesangium and renal interstitium. This study examined the effect of D -penicillamine (DPC), which inhibits collagen deposition, on disease p rogression in the remnant kidney. Methods. Two groups of 10 rats under went two-thirds nephrectomy and were pair-fed 20% casein paste (Gp 1) or the same paste supplemented with 90 mg/kg body wt per day of DPC (G p 2). Two further groups of five non-nephrectomized animals also recei ved 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 protei nuria 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 +/- 0.0 8 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, P < 0.05) and glomerul ar abnormalities, interstitial fibrosis and lymphocytic infiltration w ere less marked in Gp 2 compared with Gp 1. DPC had no effect on prote in 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 chroni c renal failure.