In Reply to ‘Finerenone: Fiddling With Hyperkalemia?’

Abstract

We thank Waitzman et al1Waitzman J. Canney M. Hiremath S. Finerenone: fiddling with hyperkalemia?.Am J Kidney Dis. 2021; 78: 760Abstract Full Text Full Text PDF Scopus (2) Google Scholar for their comments. We agree that MRAs raise hyperkalemia risk and should be used cautiously to avoid subsequent higher rates of hyperkalemia.2Juurlink D.N. Mamdani M.M. Lee D.S. et al.Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study.N Engl J Med. 2004; 351: 543-551Crossref PubMed Scopus (1371) Google Scholar While there is evidence that nonsteroidal MRAs including finerenone increase potassium to a lesser extent than spironolactone,3Pitt B. Kober L. Ponikowski P. et al.Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial.Eur Heart J. 2013; 34: 2453-2463Crossref PubMed Scopus (272) Google Scholar clinicians will need to exercise caution when using these therapies in patients with CKD. The FIDELIO-DKD protocol offers clinicians guidance on hyperkalemia mitigation and an approach to nonsteroidal MRA initiation.4Bakris G.L. Agarwal R. Anker S.D. et al.Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes.N Engl J Med. 2020; 383: 2219-2229Crossref PubMed Scopus (280) Google Scholar Initiation of finerenone only with serum potassium levels ≤4.8 mmol/L mirrors best clinical practice in that nephrologists would generally not initiate potassium-raising therapies with baseline potassium levels above this range. Importantly, beyond choosing the correct patients for these therapies, hyperkalemia management has evolved compared to the post-RALES era over 20 years ago. Novel potassium binders (patiromer, sodium zirconium cyclosilicate) are evidence-based strategies for controlling hyperkalemia while maximizing renin-angiotensin-aldosterone-system inhibitor therapies.5Agarwal R. Rossignol P. Romero A. et al.Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial.Lancet. 2019; 394: 1540-1550Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar Concomitant use of SGLT2 inhibition may also attenuate the hyperkalemia risk in heart failure patients using MRAs.6Kristensen S.L. Docherty K.F. Jhund P.S. et al.Dapagliflozin reduces the risk of hyperkalaemia in patients with heart failure and reduced ejection fraction: a secondary analysis DAPA-HF.Eur Heart J. 2020; 41: 939Google Scholar While we may have an “embarrassment of riches” to manage DKD, uptake of therapies remains unacceptably low. This is despite having data for finerenone in 2 large trials involving >13,000 participants (FIDELIO-DKD and FIGARO)—considerably more data compared to evidence for angiotensin receptor blocker monotherapy for DKD treatment in type 2 diabetes from RENAAL and IDNT. Importantly, clinical uptake of these agents will generate real-world safety and efficacy data for nonsteroidal MRAs in the current era of novel DKD medications and potassium binders. Dr Cherney has received consulting fees or speaking honoraria, or both, from Bristol Myers Squibb, Novo Nordisk, Mitsubishis-Tanabe, MAZE, Janssen, Bayer, Boehringer Ingelheim-Eli Lilly, AstraZeneca, Merck & Co, Inc, Prometic, and Sanofi; and has received operating funds from Janssen, Boehringer Ingelheim-Eli Lilly, Sanofi, AstraZeneca, and Merck & Co, Inc. The remaining authors declare that they have no relevant financial interests. Received August 3, 2021. Accepted August 3, 2021 after editorial review by an Associate Editor and a Deputy Editor. Finerenone: Fiddling With Hyperkalemia?American Journal of Kidney DiseasesVol. 78Issue 5PreviewFinerenone was recently approved by the US Food and Drug Administration for treatment of diabetic kidney disease (DKD). However, the commentary from Sridhar et al1 on the FIDELIO trial2 minimizes hyperkalemia and overstates the superiority of finerenone over other mineralocorticoid receptor antagonists (MRAs). The authors state that few patients discontinued finerenone owing to hyperkalemia (2.3% vs 0.9%). However, the enrollment criteria were crafted to minimize this, requiring a potassium level <4.8 mEq/L during screening and run-in, resulting in almost 60% exclusion. Full-Text PDF