ABSTRACT
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 (n = 27), spironolactone (50 mg, n = 25), or spironolactone (100 mg, n = 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 (P = 0.054). In the placebo-treated group, urinary 8-hydroxylated-guanosine levels increased on days 3 and 5 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.
Subject(s)
Antioxidants/therapeutic use , Kidney Transplantation/methods , Kidney/drug effects , Kidney/surgery , Living Donors , Mineralocorticoid Receptor Antagonists/therapeutic use , Oxidative Stress/drug effects , Spironolactone/therapeutic use , 8-Hydroxy-2'-Deoxyguanosine/urine , Adult , Antioxidants/adverse effects , Biomarkers/blood , Biomarkers/urine , Double-Blind Method , Female , HSP72 Heat-Shock Proteins/urine , Humans , Immunosuppressive Agents/therapeutic use , Kidney/metabolism , Kidney/physiopathology , Kidney Transplantation/adverse effects , Lipocalin-2/urine , Male , Mexico , Mineralocorticoid Receptor Antagonists/adverse effects , Pilot Projects , Spironolactone/adverse effects , Time Factors , Treatment Outcome , Young AdultABSTRACT
Se describe la experiencia del primer centro de trasplante renal en alcanzar mil trasplantes renales, efectuados en el período 1963 a 1998. Se destaca que el Centro Médico Nacional Siglo XXI efectuó el primer trasplante renal en México en octubre de 1963, siendo el segundo país de Latinoamérica, después de Argentina, quien lo efectuó en 1957. Los primeros 18 trasplantes se efectuaron entre 1963 y 1968, en los que 14 procedieron de donador cadáver (DC). Entre 1975 y 1985 se efectuaron 320 trasplantes, con gran actividad de trasplantes, sólo en 1975 se efectuaron 50 trasplantes de los que 18 procedieron de DC. A partir de 1992 el grupo de trasplante renal actual efectuó 509 trasplantes hasta 1998y acumuló la más grande experiencia de trasplantes renales en México.
