Cardiovascular and Renal Outcomes Associated With Hyperkalemia in Chronic Kidney Disease: A Hospital-Based Cohort Study

Abstract

Objective: To examine the association between hyperkalemia and long-term cardiovascular and renal outcomes in patients with chronic kidney disease.

Patients and methods: An observational retrospective cohort study was performed using a Japanese hospital claims registry, Medical Data Vision (April 1, 2008, to September 30, 2018). Of 1,208,894 patients with at least 1 potassium measurement, 167,465 patients with chronic kidney disease were selected based on International Classification of Diseases, Tenth Revision codes or estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m². Hyperkalemia was defined as at least 2 potassium measurements of 5.1 mmol/L or greater within 12 months. Normokalemic controls were patients without a record of potassium levels of 5.1 mmol/L or greater and 3.5 mmol/L or less. Changes in eGFRs and hazard ratios of death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction were assessed between propensity score-matched hyperkalemic patients and normokalemic controls.

Results: Of 16,133 hyperkalemic patients and 11,898 normokalemic controls eligible for analyses, 5859 (36.3%) patients and 5859 (49.2%) controls were selected after propensity score matching. The mean follow-up period was 3.5 years. The 3-year eGFR change in patients and controls was -5.75 and -1.79 mL/min/1.73 m², respectively. Overall, hyperkalemic patients had higher risks for death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction than controls, with hazard ratios of 4.40 (95% CI, 3.74 to 5.18), 1.95 (95% CI, 1.59 to 2.39), 5.09 (95% CI, 4.17 to 6.21), and 7.54 (95% CI, 5.73 to 9.91), respectively.

Conclusion: Hyperkalemia was associated with significant risks for mortality and adverse clinical outcomes, with more rapid decline of renal function. These findings underscore the significance of hyperkalemia as a predisposition to future adverse events in patients with chronic kidney disease.

Keywords: ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CKD, chronic kidney disease; DM, diabetes mellitus; HDL, high-density lipoprotein; HF, heart failure; ICD-10, International Classification of Diseases, Tenth Revision; LDL, low-density lipoprotein; MDV, Medical Data Vision; MRA, mineralocorticoid receptor antagonist; PS, propensity score; RAASi, renin-angiotensin-aldosterone system inhibitor; RRT, renal replacement therapy; S-K, serum potassium; eGFR, estimated glomerular filtration rate.

Figure 1

Flow diagram of patient inclusion into the study. CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; S-K = serum potassium.

Figure 2

Cumulative incidence of clinical outcomes in hyperkalemic patients and normokalemic controls after matching (A) overall follow-up period and (B) adverse clinical outcomes after 12 months. RRT = renal replacement therapy.

Figure 3

Estimated glomerular filtration rate (eGFR) changes in hyperkalemic patients and normokalemic controls after matching. LS = least square.