Objectives:
Mineralocorticoid receptor antagonist (MRA) treatment is kidney protective but not recommended to patients with advanced renal failure due to the risk of hyperkalemia and death. This study aimed to examine the impact of MRA treatment in patients with chronic kidney disease on risk of hyperkalemia and subsequent mortality.

Methods:
Rates of hyperkalemia were compared across strata of estimated glomerular filtration rate (eGFR) and MRA treatment based on cox regression using a nested case–control framework with 1 : 4 matching of patients with hyperkalemia (K+ ≥6.0 mmol/l) with controls from the Danish general population on age, sex, diabetes, and hypertension. Risk of subsequent 30-day mortality was assessed in a cohort study with comparisons across strata of eGFR and MRA treatment based on multiple Cox regression.

Results:
Thirty-two thousand four hundred twenty-six cases with hyperkalemia were matched with 127 038 controls. MRA treatment was associated with an increased rate of hyperkalemia with hazard ratios [95% confidence interval (95% CI)] of 8.28 (7.78–8.81), 5.12 (4.67–5.62), 3.58 (3.23–3.97), and 1.89 (1.60–2.23) in patients with eGFR at least 60, 45–59, 30–44, and less than 30 ml/min/1.73 m2, respectively (Reference: No MRA).

However, MRA-exposed patients had a lower 30-day mortality risk following hyperkalemia with absolute risks (95% CI) of 29.3% (27.8–31.1), 20.3% (18.7–22.4), 19.5% (17.9–21.7), and 19.7% (17.4–22.5) compared to 39.8% (38.8–40.8), 32.0% (30.7–33.1), 28.8% (27.5–31.2), and 22.5% (21.4–23.4) in patients without MRA exposure in patients with GFR at least 60, 45–59, 30–44, and less than 30 ml/min/1.7 3m2, respectively.

Conclusion:
MRA treatment was associated with an increased rate of hyperkalemia but decreased risk of subsequent 30-day mortality across all stages of renal impairment.