Journal Article

Recovery from ischemic acute kidney injury by spironolactone administration

Katy Sánchez-Pozos, Jonatan Barrera-Chimal, Juan Garzón-Muvdi, Rosalba Pérez-Villalva, Roxana Rodríguez-Romo, Cristino Cruz, Gerardo Gamba and Norma A. Bobadilla

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 8, pages 3160-3169
Published in print August 2012 | ISSN: 0931-0509
Published online April 2012 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfs014
Recovery from ischemic acute kidney injury by spironolactone administration

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Background

Prophylactic mineralocorticoid receptor (MR) antagonism with spironolactone (Sp) in rats completely prevents renal damage induced by ischemia. Because acute renal ischemia cannot typically be predicted, this study was designed to investigate whether Sp could prevent renal injury after an ischemic/reperfusion insult.

Methods

Six groups of male Wistar rats were studied: rats that received a sham abdominal operation (S); rats that underwent 20 min of ischemia and reperfusion for 24 h (I/R) and four groups of rats treated with Sp (20 mg/kg) 0, 3, 6 or 9 h after ischemia.

Results

As expected, I/R resulted in renal dysfunction characterized by a fall in renal blood flow and glomerular filtration rate and severe tubular injury which was confirmed by a significant increase in tubular damage biomarkers including kidney injury molecule-1, heat shock protein 72 and urinary protein excretion. The renal injury induced by I/R was in part due to Rho-kinase, endothelin and angiotensin II type 1 receptor upregulation. Interestingly, Sp administration at 0 and 3 h after ischemia completely reversed and prevented the damage induced by I/R. The protection induced by Sp given 6 h after ischemia was partial, but no protection was observed by administering Sp 9 h after ischemia.

Conclusion

Our results show that MR antagonism administered, either immediately or 3 h after I/R, effectively prevented ischemic acute renal injury, indicating that spironolactone is a promising agent for preventing acute kidney injury once an ischemic insult has occurred.

Keywords: AKI treatment; endothelin; renal dysfunction; Rho-kinase

Journal Article.  6604 words.  Illustrated.

Subjects: Nephrology

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