Hyperkalemia Management in Older Adults With Diabetic Kidney Disease Receiving Renin-Angiotensin-Aldosterone System Inhibitors: A Post Hoc Analysis of the AMETHYST-DN Clinical Trial

Abstract

Rationale & objective: Older people are more likely to have reduced kidney function and multiple comorbid conditions predisposing them to hyperkalemia. This post hoc subgroup analysis aimed to evaluate the effectiveness of patiromer, a sodium-free nonabsorbed polymer, in lowering serum potassium levels in older patients receiving a renin-angiotensin-aldosterone system inhibitor with chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and hypertension.

Study design: Post hoc subgroup analysis of the randomized open-label AMETHYST-DN clinical trial.

Setting & participants: Multicenter clinical trial. Individuals 75 years and older with CKD, T2DM, hypertension, and hyperkalemia at baseline (N = 60; mean age, 77 years; 30 men [50%]; mean estimated glomerular filtration rate, 41.6 ± 14.3 mL/min/1.73 m2).

Intervention: Patients with hyperkalemia were randomly assigned to receive patiromer at doses ranging from 4.2 to 16.8 g twice daily.

Outcomes: We evaluated changesin serum potassium levels from baseline to week 4 and time points through 52 weeks. Long-term safety and tolerability were assessed through the end of 52 weeks and included frequency of adverse events, clinical laboratory measurements, and vital signs.

Results: Of 306 AMETHYST-DN participants, 60 were 75 years or older. All 60 patients had CKD and T2DM; 37% had heart failure. At screening, patients had an estimated glomerular filtration rate of 42 mL/min/1.73 m2, median urinary albumin-creatinine ratio of 127 mg/g, and baseline mean serum potassium level of 5.19 mEq/L. Mean serum potassium level was reduced at each time point from the first postbaseline visit (day 3) through week 52.

Limitations: This small subgroup analysis was not prespecified and therefore randomization was lost; thus, it should be considered hypothesis generating.

Conclusions: Among older patients with hyperkalemia and diabetic kidney disease, treatment with patiromer resulted in significant reductions in serum potassium levels after 4 weeks and lasted through 52 weeks. Patiromer was effective in lowering serum potassium levels and was well tolerated in older patients.

Funding: Vifor Pharma, Inc.

Trial registration: NCT01371747.

Keywords: Chronic kidney disease; diabetes; geriatrics; hyperkalemia; patiromer.

© 2021 The Authors.

Figures

Graphical abstract

Figure 1

AMETHYST-DN study design. ∗Estimated glomerular filtration rate (eGFR) of 15 to 2. †Before screening. ‡Primary end points. §Renin-angiotensin-aldosterone system inhibitor (RAASi) therapy was continued after patiromer treatment discontinuation only in patients who were normokalemic (mean serum potassium ≤ 5.0 mEq/L) at the end of the maintenance phase. Abbreviations: ACR, albumin-creatinine ratio; BP, blood pressure; CKD, chronic kidney disease; HK, hyperkalemia; spiro, spironolactone; T2DM, type 2 diabetes mellitus.

Figure 2

Achievement of normokalemia. Abbreviation: ET, end of treatment.

Figure 3

Mean serum potassium level at each time point. Abbreviations: BL, baseline; ET, end of treatment.