Protective role of enalapril for chronic tubulointerstitial lesions of hyperoxaluria

Purpose: Hyperoxaluria is a recognized cause of tubulointerstitial lesions and it may contribute to chronic renal failure. In previous studies we demo nstrated that enalapril was effective against the progression of tubulointe rstitial lesions in a 4-week hyperoxaluria rat model. We evaluated whether the action of enalapril on the tubulointerstitial lesions produced by hyper oxaluria persisted for a long period. Materials and Methods: Two-month-old male Sprague-Dawley rats were divided into 4 groups of 12 each, including 1-control animals given tap water, 2-an imals with hyperoxaluria, 3-animals with hyperoxaluria plus enalapril, 4-an imals with enalapril. Hyperoxaluria in groups 2 and 3 rats was induced by a dministering 1% ethylene glycol, a precursor for oxalates, in the tap water continuously throughout the whole study. Meanwhile, groups 3 and 4 receive d 20 mg./l. enalapril in the drinking water. At the end of the study renal tubulointerstitial lesions were evaluated by immunostaining using monoclona l antibodies against macrophage infiltrates (ED1), tubulointerstitial alpha -smooth muscle actin and transforming growth factor-beta1. The lesions wer e quantified by semiquantitative scores. Creatinine clearance and urinary a lbumin excretion were also determined. Results: There was no difference in urine oxalate excretion in groups 2 and 3. Group 3 rats treated with enalapril showed fewer tubulointerstitial les ions than nontreated group 2 rats, as indicated by the mean scores plus or minus standard error of mean for inflammatory infiltrate (2.16 +/- 0.2 vers us 0.83 +/- 0.16), tubular atrophy (2 +/- 0.27 versus 0.66 +/- 0.14), inter stitial fibrosis (2.5 +/- 0.15 versus 0.5 +/- 0.1), glomerular ED1 (1.75 +/ - 0.25 versus 0.16 +/- 0.11), interstitial ED1 (2.33 +/- 0.18 versus 0.58 /-: 0.10) tubular transforming growth factor-beta1 (2.09 +/-. 0.08 versus 0 .91 +/- 0.14), interstitial transforming growth factor-beta1 (2.33 +/- 0.22 versus 0.66 +/- 0.12), tubulointerstitial alpha -smooth muscle actin (2.91 +/- 0.22 versus 0.83 +/- 0.16), lower urinary albumin excretion (35.5 +/- 2.7 mg. daily versus 10.9 +/- 1) and higher creatinine clearance (2.29 +/- 0.04 ml. per minute versus 2.54 +/- 0.03, all p <0.05). Conclusions: Based on our results we believe that enalapril would provide a beneficial effect against chronic tubulointerstitial lesions caused by oxa lates.