Renoprotective Effect of Angiotensin Converting Enzyme Inhibitor and Angiotensin Receptor Blocker in Chronic Uremic Rats: Comparison of Early Treatment with Delayed Treatment / 대한신장학회잡지

ABSTRACT

BACKGROUND: We compared the renoprotective effect of angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) between early treatment and delayed treatment in chronic uremic rats. METHODS: Male Sprague-Dawley rats underwent 5/6 nephrectomy or sham operation (sham) and received no treatment (UC), enalapril (E) 100 mg/L, candesartan cilexetil (C) 10 mg/L or combination of E and C in drinking water. Some rats began to be treated from the next day of 5/6 nephrectomy (early group) and the others began from 12 weeks of 5/6 nephrectomy (delayed group). Blood pressure, renal function, proteinuria, histological changes and renal cortical TGFbeta1 expression were observed for 24 weeks. RESULTS: Blood pressure was significantly lower in E, C or E+C of both early and delayed group than in UC. Particularly blood pressure in E+C of early group was lower than in E or C. In E, C or E+C of both early and delayed group, BUN was lower and creatinine clearance was higher compared with UC. Proteinuria was also significantly lower in E, C or E+C of both early and delayed group compared with UC. In addition, remnant kidney weight in E, C or E+C of early and delayed group was significantly lower compared with UC, representing less renal hypertrophy. On the histological examination, glomerulosclerosis score, interstitial fibrosis score and the number of infiltrated glomerular macrophage were significantly lower in E, C or E+C of both early and delayed group compared with UC. Furthermore, renal cortical TGF-beta1 expression was also lower in E, C or E+C of both early and delayed group compared with UC. CONCLUSION: ACEi and ARB have renoprotective effect biochemically and histologically even though the treatment was delayed until moderate chronic renal failure had occurred.