European review for medical and pharmacological sciences 2014-10-01

Paricalcitol counteracts the increased contrast induced nephropathy caused by renin-angiotensin-aldosterone system blockade therapy in a rat model.

I Sahin, B Ozkaynak, M Sar, H I Biter, B Mert, E Okuyan, N Kayalar, M M Can, B Güngör, V Erentug, M H Dinckal

Index: Eur. Rev. Med. Pharmacol. Sci. 18(19) , 2895-902, (2014)

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Abstract

The effect of vitamin D and renin-angiotensin-aldosterone system blockade medications in pathophysiology of contrast induced nephropathy (CIN) is controversial. The effects of paricalcitol (active vitamin D analogue) and losartan treatments in an experimental model of CIN were investigated in this study.Thirty-six male Wistar albino rats were examined in five treatment groups. Placebo group (Group A; n = 4) received no active medication; control group (Group B; n = 8) received only contrast media (CM); Group C (n = 8) received paricalcitol; Group D (n = 8) received losartan and Group E (n = 8) received paricalcitol plus losartan. CIN was induced by NG-nitro-L-arginine methyl ester and indomethacin before iohexol injection. Renal histopathological findings were categorized and renal immunohistochemical examinations by caspase-3 rabbit primary antibody were performed.Creatinine and cystatin C levels significantly increased in the treatment groups, compared to Group A. However, creatinine levels were not significantly increased in Groups C, D and E compared to Group B. Compared to Group B, a significant increase of cystatin C levels was observed in Group D (p < 0.01). In Group E, when paricalcitol treatment was added to losartan treatment, cystatin C levels were similar to Group B (p = 1.00). In histopathological and immunohistochemical examination frequency of Grade 2/3 tubular necrosis and renal caspase 3 activity scores were significantly higher in the losartan treatment group compared to the other treatment groups. The histopathological effects related to losartan treatment were found to be reversed when paricalcitol treatment was combined.Our findings suggest that paricalcitol treatment counteracts increased contrast induced nephropathy caused by losartan. These findings warrant further clinical studies to investigate the benefit of paricalcitol in CIN prophylaxis.