Spironolactone reduces oxidative stress in living donor kidney transplantation: a randomized controlled trial

• Published in: American journal of physiology. Renal physiology Vol. 317; no. 3; pp. F519 - F528
• Main Authors: Morales-Buenrostro, Luis Eduardo, Ortega-Trejo, Juan Antonio, Pérez-Villalva, Rosalba, Marino, Lluvia A, González-Bobadilla, Yvett, Juárez, Hilda, Zamora-Mejía, Flor M, González, Norma, Espinoza, Ramón, Barrera-Chimal, Jonatan, Bobadilla, Norma A
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.09.2019
• Subjects: 8-Hydroxy-2'-Deoxyguanosine - urine; Adult; Animal models; Antioxidants - adverse effects; Antioxidants - therapeutic use; Biomarkers - blood; Biomarkers - urine; Corticosteroids; Creatinine; Cross-match; Deoxyguanosine; Double-Blind Method; Female; Gelatinase; Guanosine; Heat shock proteins; HSP72 Heat-Shock Proteins - urine; Humans; Immunosuppression; Immunosuppressive Agents - therapeutic use; Interleukin 2; Interleukin 2 receptors; Ischemia; Kidney - drug effects; Kidney - metabolism; Kidney - physiopathology; Kidney - surgery; Kidney transplantation; Kidney Transplantation - adverse effects; Kidney Transplantation - methods; Lipocalin; Lipocalin-2 - urine; Living Donors; Male; Mexico; Mineralocorticoid Receptor Antagonists - adverse effects; Mineralocorticoid Receptor Antagonists - therapeutic use; Mycophenolate mofetil; Mycophenolic acid; Neutrophils; Oxidative stress; Oxidative Stress - drug effects; Pilot Projects; Potassium; Reperfusion; Spironolactone - adverse effects; Spironolactone - therapeutic use; Tacrolimus; Time Factors; Transplants & implants; Treatment Outcome; Urine; Young Adult; Mexico; postischemic injury; mineralocorticoid receptor blockade; kidney transplantation
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00606.2018

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 (KT). In the present 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 KT recipients. We included KT recipients aged 18 yr or older who received immunosuppression therapy with IL-2 receptor antagonist, mycophenolate mofetil, corticosteroids, and tacrolimus with negative cross-match, and compatible blood group. Patients were randomized to receive placebo ( = 27), spironolactone (50 mg, = 25), or spironolactone (100 mg, = 25). Treatment was given from 3 days before and up to 5 days after KT. Serum creatinine, K , urine neutrophil gelatinase-associated lipocalin-2, heat shock protein 72, and 8-hydroxy-2-deoxyguanosine levels were assessed. As expected, kidney function was improved after KT. Serum K remained in the normal range along the study. There was no significant effect of spironolactone on urinary neutrophil gelatinase-associated lipocalin-2 levels, whereas the increase in urinary heat shock protein 72 levels tended to be less intense in the 100 mg spironolactone-treated group ( = 0.054). In the placebo-treated group, urinary 8-hydroxylated-guanosine levels increased on and after transplantation. This effect was prevented in patients that received spironolactone. In conclusion, spironolactone reduces the acute increase in urinary oxidative stress in living donor KT recipients.