Hyperkalemia in Real-World Patients Under Continuous Medical Care in Japan

Abstract

Introduction: An abnormal serum potassium (S-K) level is an important electrolyte disturbance. However, its relation to clinical outcomes in real-world patients, particularly hyperkalemia burden, is not extensively studied.

Methods: An observational retrospective cohort study using a Japanese hospital claims database was done (April 2008-September 2017; N = 1,022,087). Associations between index S-K level and 3-year survival were modeled using cubic spline regression. Cox regression model was applied to estimate the time to death according to different S-K levels. Prevalence, patient characteristics, treatment patterns, and management of patients with hyperkalemia from first episode were assessed.

Results: Hyperkalemia prevalence was 67.9 (95% confidence interval [CI]: 67.1-68.8) per 1000 and increased in patients with chronic kidney disease (CKD) (227.9; 95% CI: 224.3-231.5), heart failure (134.0; 95% CI: 131.2-136.8), and renin-angiotensin-aldosterone system inhibitor (RAASi) use (142.2; 95% CI: 139.6-144.7). U-shaped associations between S-K level and 3-year survival were observed with nadir 4.0 mEq/l. The risk of death was increased at S-K 5.1-5.4 mEq with hazard ratio of 7.6 (95% CI: 7.2-8.0). The 3-year mortality rate in patients with CKD stages 3a, 3b, 4, and 5 with normokalemia were 1.51%, 3.93%, 10.86%, and 12.09%, whereas that in patients with CKD stage 3a at S-K 5.1-5.4, 5.5-5.9, and ≥6.0 mEq/l increased to 10.31%, 11.43%, and 22.64%, respectively. Despite treatment with loop diuretics (18.5%) and potassium binders (5.8%), >30% of patients had persistently high S-K (≥5.1 mEq/l).

Conclusion: This study provides real-world insight on hyperkalemia based on a large number of patients with various medical backgrounds.

Keywords: chronic kidney disease; congestive heart failure; hyperkalemia; renin angiotensin system; renin-angiotensin-aldosterone inhibitor.

Graphical abstract

Figure 1

Flow diagram of patient inclusion into the study. S-K, serum potassium.

Figure 2

Cubic spline analysis of the 3-year incidence of in-hospital death according to serum potassium levels. Five knots at the 17th, 33th, 50th, 67th, and 83th percentiles were used.

Figure 3

Cumulative incidence of death in hyperkalemic and normokalemic (serum potassium [S-K] 3.6–5.0 mEq/l) patients. CKD, chronic kidney disease; DM, diabetes mellitus; HF, heart failure; HTN, hypertension.

Figure 4

Cumulative incidence of death in hyperkalemic and normokalemic (serum potassium [S-K] 3.6–5.0 mEq/l) patients according to chronic kidney disease (CKD) stages and index S-K levels.

Figure 5

Cumulative incidence of first hyperkalemia episode. (a) Overall. (b) Chronic kidney disease (CKD). (c) Diabetes mellitus (DM). (d) Heart failure (HF). (e) Hypertension (HTN). RAASi, renin-angiotensin-aldosterone inhibitor; CI, confidence interval.

Figure 6

Cumulative incidence of hyperkalemia episode by chronic kidney disease (CKD) stages. (a) Serum potassium (S-K) ≥5.1 mEq/l. (b) S-K ≥5.5 mEq/l. (c) S-K ≥6.0 mEq/l.

Figure 7

Kaplan-Meier analysis of time to discontinuation of initial potassium binder treatment. Discontinuation of potassium binders was defined as potassium binders not being prescribed ≥30-day gap after the last day of the supply of the previous prescription during the follow-up period. CI, confidence interval; CKD, chronic kidney disease; DM, diabetes mellitus; HF, heart failure; HTN, hypertension.

Figure 8

Control status of serum potassium level after the index hyperkalemia episode in (a) overall patients and (b) patients taking potassium binders. S-K, serum potassium; CKD, chronic kidney disease; DM, diabetes mellitus; HF, heart failure; HTN, hypertension.

Figure 9

Cumulative incidence curve of recurrent hyperkalemia episodes for (a) serum potassium (S-K) ≥5.1 mEq/l, (b) S-K ≥5.5 mEq/l, and (c) S-K ≥6.0 mEq/l. CKD, chronic kidney disease; DM, diabetes mellitus; HF, heart failure; HTN, hypertension.