title: [Novel action of aldosterone in CsA nephrotoxicity].
abstract: Calcineurin inhibitors are helpful immunosuppressive agents in clinical practice. Thanks to their lower cost respect with new immunosuppressive therapy, calcineurin inhibitors in our country continue being the most used treatment in solid organ transplant recipients or patients with autoimmune disease. In the 80's decade cyclosporine A (CsA) was introduced as the first calcineurin inhibitor transforming the immunosuppression therapy. Up to date, many articles evaluating beneficial and adverse effects of CsA have been published. In this review, basic aspects and actions of CsA are analyzed together with studies from our laboratory that pointed out the pathophysiological role of aldosterone as a mediator of functional and structural changes that are observed in CsA nephrotoxicity. Based in our findings, we proposed that in CsA nephrotoxicity, the aldosterone mediates renal vasoconstriction and enhances TGFbeta expression promoting the development of nefrotoxicity. Finally, results from our laboratory and others allow us to suggest that aldosterone receptors blockade with spironolactone or eplerone could be a pharmacological therapy to reduce or prevent acute and chronic CsA nephrotoxicity in transplant recipients.
authors.affiliation: Unidad de Fisiología Molecular, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, DF.
authors.forename: Jazmin M
authors.initials: JM
authors.lastname: Pérez-Rojas
authors.forename: Norma A
authors.initials: NA
authors.lastname: Bobadilla
mesh_terms: D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D065095:Calcineurin Inhibitors; D002318:Cardiovascular Diseases / Q000503:physiopathology; D016572:Cyclosporine / Q000009:adverse effects*; D018450:Disease Progression; D000077545:Eplerenone; D005609:Free Radicals; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D000451:Mineralocorticoid Receptor Antagonists; D050778:NFATC Transcription Factors / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D012079:Renal Circulation / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology; D013148:Spironolactone / Q000031:analogs & derivatives / Q000627:therapeutic use; D013564:Sympathetic Nervous System / Q000503:physiopathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology; D014181:Transplantation Immunology; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D065095:Calcineurin Inhibitors; D005609:Free Radicals; D007166:Immunosuppressive Agents; D000451:Mineralocorticoid Receptor Antagonists; D050778:NFATC Transcription Factors; D018161:Receptors, Mineralocorticoid; D016212:Transforming Growth Factor beta; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D016572:Cyclosporine