FC084: Mineralocorticoid Receptor Antagonist Treatment in Patients with Renal Insufficiency and Associated Risk of Hyperkalemia and Death
Authors: Møller Sara , Torp Christian , Schou Morten , Gislason Gunnar , Carlson Nicholas , Lindhardt Morten 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Mineralocorticoid receptor antagonist treatment is kidney protective but not recommended in patients with advanced renal failure due to perceived risk of hyperkalaemia and death. The aim of the present study was to examine the impact of mineralocorticoid receptor antagonist treatment in progressive chronic kidney disease on risk of hyperkalaemia and to evaluate subsequent attributable mortality.

METHOD
Based on data from multiple nationwide health care registers, all Danish residents &gt;18 years with more than or equal to one recorded plasma creatinine measurement were identified in Denmark between 2008 and 2021, and followed until either incident hyperkalaemia &gt;6 mmol/L, death or end-of follow-up (5 October 2021). Cases were identified based on incident hyperkalaemia and subsequently matched with four controls without hyperkalaemia. eGFR was computed based on the latest creatinine measurement until 30 days prior to index using the CKD-EPI equation. Patients with no recorded creatinine measurement within 2 years until 30 days prior of index were excluded. Mineralocorticoid receptor antagonist associated susceptibility for hyperkalaemia was computed across strata of estimated glomerular filtration rate (eGFR) (&gt;60, 30–60 and &lt;30 mL/min/1.73 m2) in a conditional logistic regression model comparing rate of hyperkalaemia with stratification of baseline hazard rate by age, gender, diabetes and hypertension. Model fitting was accomplished using a nested case–control design with 1:4 risk-set matching of cases with age-, gender-, diabetes- and hypertension-matched controls. Subsequent risk of 30-day mortality was assessed in a retrospective cohort study including patients with hyperkalemia only. Patients were followed from the date of hyperkalemia until death, 30 days or end of follow-up (5 October 2021) with comparison of MRA-attributable mortality across strata of eGFR based on the Kaplan–Meier estimator and multiple Cox regression models adjusted for age and gender.

RESULTS
From a population of 4 255 962 Danish citizens with recorded plasma creatinine, a total of 51 775 patients with incident hyperkalaemia were identified between 2008 and 2021. Pre-existing plasma creatinine permitting estimation of renal function was available in 34 442 (66.5%) patients. The 34 442 cases with incident hyperkalaemia were matched 1:4 with 131 410 controls. Gender distribution was 57% male, median age was 73.5 (IQR 64.0–82.0) years and median eGFR was 74 (IQR 55–89) mL/min/1.73 m2.
Mineralocorticoid receptor antagonist treatment was associated with increased rates of hyperkalaemia with HRs of 8.32 (95% CI: 7.82–8.85), 4.55 (95% CI: 4.26–4.86) and 2.00 (95% CI: 1.71–2.32) in patients with eGFR &gt; 60 mL/min/1.73 m2 eGFR 30–60 mL/min/1.73 m2 and eGFR &lt; 30 mL/min/1.73 m2 respectively (reference = No mineralocorticoid receptor antagonist treatment).
30-day mortality in patients with hyperkalaemia stratified on mineralocorticoid receptor antagonist treatment is shown in Figures 1 and 2. Overall, mineralocorticoid receptor antagonist treatment was associated with lower subsequent mortality: HR 0.84 (95% CI: 0.78–0.90); P &lt; 0.001, 0.67 (95% CI: 0.62–0.73); P &lt; 0.001 and 0.98 (95% CI: 0.86–1.1); P = 0.77 for eGFR &gt; 60 mL/min/1.73 m2 30–60 mL/min/1.73 m2 and &lt;30 mL/min/1.73 m2 respectively (reference = mineralocorticoid receptor antagonist).

CONCLUSION
Although mineralocorticoid receptor antagonist treatment was associated with increased risk of hyperkalaemia for all strata of kidney impairment, subsequent 30-day mortality was lower compared with patients with corresponding kidney function without mineralocorticoid receptor antagonist treatment.