*Purpose: Mineralocorticoid receptor antagonism prevents acute kidney injury induced by ischemia/reperfusion in rodent and pig preclinical models. In a pilot study, we showed that spironolactone (25 mg) reduced oxidative stress after 5 days of kidney transplant. In this study, we investigated the effects of higher doses (50 and 100 mg) of spironolactone on kidney function, tubular injury markers and oxidative stress in living-donor kidney transplant recipients.

*Methods: Kidney transplant recipients aged 18 years or older, who received immunosuppression therapy with interleukin-2 receptor antagonist, mycophenolate mofetil, corticosteroids and tacrolimus, with negative cross-match, and compatible blood group were included. Patients were randomized to receive placebo (n=27), spironolactone 50 mg (n=25) or spironolactone 100 mg (n=25). Treatment was given from three days before and up to 5 days after kidney transplant. Plasma creatinine, potassium, urine neutrophil gelatinase associated lipocalin-2 (NGAL), heat shock protein 72 (Hsp72) and 8-hydroxylated-guanosine levels were assessed.

*Results: As expected, kidney function was improved after kidney transplantation. Plasma potassium was not affected during the studied period. There was no significant effect of spironolactone on urinary NGAL levels, whereas, the increase in urinary Hsp72 levels tended to be less intense in the spironolactone 100 mg group (p=0.054). In the placebo group, urinary 8-hydroxylated-guanosine levels increased at day 3 and 5 after transplantation. This effect was significantly prevented in the patients receiving Spironolactone at 50 and 100 mg.

*Conclusions: Spironolactone reduces the acute increase in urinary oxidative stress in living-donor kidney transplant recipients.

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