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Background  We studied whether endothelin receptor antagonist and calcimimetic treatments influence renal damage and kidney renin-angiotensin (RA) components in adenine-induced chronic renal insufficiency (CRI).    Methods  Male Wistar rats ( n  = 80) were divided into 5 groups for 12 weeks: control ( n  = 12), 0.3% adenine (Ade;  n  = 20), Ade + 50 mg/kg/day sitaxentan ( n  = 16), Ade + 20 mg/kg/day cinacalcet (n = 16), and Ade + sitaxentan + cinacalcet (n = 16). Blood pressure (BP) was measured using tail-cuff, kidney histology was examined, and RA components measured using RT-qPCR.    Results  Adenine caused tubulointerstitial damage with severe CRI, anemia, hyperphosphatemia, 1.8-fold increase in urinary calcium excretion, and 3.5-fold and 18-fold increases in plasma creatinine and PTH, respectively. Sitaxentan alleviated tubular atrophy, while sitaxentan + cinacalcet combination reduced interstitial inflammation, tubular dilatation and atrophy in adenine-rats. Adenine diet did not influence kidney angiotensin converting enzyme (ACE) and AT 4  receptor mRNA, but reduced mRNA of renin, AT 1a , AT 2 , (pro)renin receptor and Mas to 40–60%, and suppressed ACE2 to 6% of that in controls. Sitaxentan reduced BP by 8 mmHg, creatinine, urea, and phosphate concentrations by 16–24%, and PTH by 42%. Cinacalcet did not influence BP or creatinine, but reduced PTH by 84%, and increased hemoglobin by 28% in adenine-rats. The treatments further reduced renin mRNA by 40%, while combined treatment normalized plasma PTH, urinary calcium, and increased ACE2 mRNA 2.5-fold versus the Ade group ( p  < 0.001).    Conclusions  In adenine-induced interstitial nephritis, sitaxentan improved renal function and tubular atrophy. Sitaxentan and cinacalcet reduced kidney renin mRNA by 40%, while their combination alleviated tubulointerstitial damage and urinary calcium loss, and increased kidney tissue ACE2 mRNA.    Electronic supplementary material  The online version of this article (10.1186/s12882-017-0742-z) contains supplementary material, which is available to authorized users.

Endothelin A receptor blocker and calcimimetic in the adenine rat model of chronic renal insufficiency