D-penicillamine reduces renal injury in the remnant model of chronic renal failure in the rat.
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 collagen deposition, on disease progression in the remnant kidney.


METHODS
Two groups of 10 rats underwent 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 (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, P < 0.05) 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.
Throssell
D
D
Department of Nephrology, Leicester General Hospital, UK.
Brown
J
J
Furness
P N
PN
Rutty
G
G
Walls
J
J
Harris
K P
KP
D000818:Animals; D001794:Blood Pressure; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D009392:Nephrectomy; D010396:Penicillamine / Q000627:therapeutic use*; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
D003094:Collagen; D010396:Penicillamine