Captopril slows the progression of chronic renal disease in partially nephrectomized rats.
The effect of captopril, an angiotensin-converting enzyme inhibitor, on the progression of chronic renal disease was studied in rats subjected to partial nephrectomy. Following ablation of approximately 70% of their renal mass, rats were divided into three treatment groups: group I received a placebo treatment; group II received daily po administrations of captopril; group III received captopril at the same dosage schedule as group II, but the drug was not given for 4 weeks in the middle of the treatment period. Measurements of renal function were performed at 4-week intervals, and light microscopic evaluation of the remnant kidneys was performed following 19 weeks of treatment. Deterioration of renal function, as measured by endogenous creatinine clearance, plasma creatinine, and plasma urea nitrogen, progressed more rapidly in group I than the other two groups. Twenty-four-hour urinary protein excretion was higher in group I than the others, except in group III following the 4-week period when captopril was not administered. Morphologic damage in the remnant kidney was significantly greater in group I than group II (p = 0.007). The renal lesions in the rats of group III were intermediate in severity. Histopathologic ranking of the remnant kidneys was correlated with antemortem laboratory parameters (r greater than or equal to 0.50; p less than 0.05). In a second experiment, similarly nephrectomized rats receiving po captopril daily had significantly longer survival, at 260 days, postnephrectomy than rats receiving a placebo (p = 0.0045). We conclude that captopril retards the progression of renal damage and increases survival time in this model of chronic renal disease. The mechanism may involve the alteration of potentially harmful intraglomerular hemodynamic changes which occur in the remnant kidney model.
D000818:Animals; D001806:Blood Urea Nitrogen; D002216:Captopril / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D006439:Hemodynamics; D007668:Kidney / Q000098:blood supply; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D007677:Kidney Function Tests; D008297:Male; D009392:Nephrectomy; D011392:Proline / Q000031:analogs & derivatives*; D011507:Proteinuria / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains
D011392:Proline; D002216:Captopril; D003404:Creatinine