Limits...
Safety of Eplerenone for Kidney-Transplant Recipients with Impaired Renal Function and Receiving Cyclosporine A.

Bertocchio JP, Barbe C, Lavaud S, Toupance O, Nazeyrollas P, Jaisser F, Rieu P - PLoS ONE (2016)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Nephrology, Dialysis and Transplantation Unit, Reims University Hospital, Avenue Cognacq Jay, 51092 Reims CEDEX, France.

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.

Trial registration: ClinicalTrials.gov NCT01834768.

No MeSH data available.


Related in: MedlinePlus

Design of the EpleCsAT: Safety trial.Sequential inclusion was performed: 14 patients during step 1; then 17 new patients during step 2.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4835088&req=5

pone.0153635.g001: Design of the EpleCsAT: Safety trial.Sequential inclusion was performed: 14 patients during step 1; then 17 new patients during step 2.

Mentions: We performed the study by using a two-steps Simon’s plan (Fig 1) [17]. During the first step, 14 patients took eplerenone 25 mg/d for 8 weeks. This posology was chosen to be the minimum efficient. If three or more adverse events occurred, then study had to be discontinued. If not, 17 new patients were included within step 2 and also received the same treatment for 8 weeks. If four or more adverse events occurred in both steps (1 and 2), then study had to be discontinued, and the alternate hypothesis (a risk of adverse events >20%) could not be rejected: i.e., the safety of eplerenone could not be concluded. If not, we could conclude that eplerenone at 25 mg/d could be safety used in such a population.


Safety of Eplerenone for Kidney-Transplant Recipients with Impaired Renal Function and Receiving Cyclosporine A.

Bertocchio JP, Barbe C, Lavaud S, Toupance O, Nazeyrollas P, Jaisser F, Rieu P - PLoS ONE (2016)

Design of the EpleCsAT: Safety trial.Sequential inclusion was performed: 14 patients during step 1; then 17 new patients during step 2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835088&req=5

pone.0153635.g001: Design of the EpleCsAT: Safety trial.Sequential inclusion was performed: 14 patients during step 1; then 17 new patients during step 2.
Mentions: We performed the study by using a two-steps Simon’s plan (Fig 1) [17]. During the first step, 14 patients took eplerenone 25 mg/d for 8 weeks. This posology was chosen to be the minimum efficient. If three or more adverse events occurred, then study had to be discontinued. If not, 17 new patients were included within step 2 and also received the same treatment for 8 weeks. If four or more adverse events occurred in both steps (1 and 2), then study had to be discontinued, and the alternate hypothesis (a risk of adverse events >20%) could not be rejected: i.e., the safety of eplerenone could not be concluded. If not, we could conclude that eplerenone at 25 mg/d could be safety used in such a population.

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Nephrology, Dialysis and Transplantation Unit, Reims University Hospital, Avenue Cognacq Jay, 51092 Reims CEDEX, France.

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.

Trial registration: ClinicalTrials.gov NCT01834768.

No MeSH data available.


Related in: MedlinePlus