title: Safety of Eplerenone for Kidney-Transplant Recipients with Impaired Renal Function and Receiving Cyclosporine A.
abstract: BACKGROUND
  Animal studies have highlighted the role of vascular mineralocorticoid receptor during Cyclosporine A-induced nephrotoxicity. Mineralocorticoid receptor antagonists could improve kidney survival but are not commonly used during renal impairment and in association with several immunosuppressive drugs due to a supposed higher risk of adverse events. We tested the tolerance of eplerenone according to its expected adverse events: hyperkalemia, metabolic acidosis, hypotension, acute kidney failure, or any other adverse event.
  
  
  METHODS
  We conducted a single-center, prospective, open-label study in 31 kidney-transplant recipients with impaired renal function (30 and 50 mL/min/1.73 m2) and receiving cyclosporine A. All patients received eplerenone 25 mg/d for 8 weeks. Serum potassium, renal function and expected adverse events were closely monitored.
  
  
  RESULTS
  Eight patients experienced mild hyperkalemia (>5 mmol/L), one moderate hyperkalemia (>5.5 mmol/L) and had to receive potassium-exchange resin. No severe hyperkalemia (>6 mmol/L) occurred. One acute kidney failure was observed, secondary to diarrhea. Basal serum potassium and bicarbonate were independently associated with a higher risk of developing mild hyperkalemia (>5 mmol/L) under treatment (OR 6.5, p = 0.003 and 0.7, p = 0.007, respectively). A cut-off value of 4.35 mmol/L for basal serum potassium was the best factor to predict the risk of developing mild hyperkalemia (>5 mmol/L).
  
  
  CONCLUSIONS
  Until eGFR falls to 30 mL/min/1.73 m2, eplerenone could be safely given to kidney-transplant recipients receiving cyclosporine A, if kalemia is closely monitored. When renal function is impaired and if basal kalemia is >4.35 mmol/L, then clinicians should properly balance risk and benefit of eplerenone use and offer dietary advice. An adequately powered prospective randomized study is now needed to test its efficiency (and safety) in this population.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01834768.
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Reims University Hospital, Avenue Cognacq Jay, 51092 Reims CEDEX, France.|INSERM UMRS 1138 -Team 1, Research Centre of Cordeliers, 15 rue de l'école de médecine, 75006 Paris CEDEX, France.
authors.forename: Jean-Philippe
authors.identifier: http://orcid.org/0000-0002-4104-702X
authors.initials: JP
authors.lastname: Bertocchio
authors.affiliation: Biostatistics and methodology unit, Reims University Hospital, Avenue Cognacq Jay, 51092 Reims CEDEX, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Barbe
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Reims University Hospital, Avenue Cognacq Jay, 51092 Reims CEDEX, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lavaud
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Reims University Hospital, Avenue Cognacq Jay, 51092 Reims CEDEX, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Toupance
authors.affiliation: Biostatistics and methodology unit, Reims University Hospital, Avenue Cognacq Jay, 51092 Reims CEDEX, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Nazeyrollas
authors.affiliation: INSERM UMRS 1138 -Team 1, Research Centre of Cordeliers, 15 rue de l'école de médecine, 75006 Paris CEDEX, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Jaisser
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Reims University Hospital, Avenue Cognacq Jay, 51092 Reims CEDEX, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rieu
mesh_terms: D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D000077545:Eplerenone; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D011446:Prospective Studies; D012372:ROC Curve; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000209:etiology; D012449:Safety; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D066027:Transplant Recipients
chemical_list: D007166:Immunosuppressive Agents; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D016572:Cyclosporine