Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis.

Csaba P Kövesdy ,Gabriel Chodick,Atsushi Hirayama,Adeera Levin,Dorothea Nitsch,Stein Hallan,Takeshi Hasegawa,Yingying Sang,Josef Coresh,Varda Shalev,Kunihiro Matsushita,Gijs W D Landman ,Juan Jesús Carrero ,David C Wheeler ,Hiddo Lambers Heerspink ,Nigel J Brunskill

doi:10.1093/eurheartj/ehy100

Abstract

Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium. We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1217986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26-1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts. Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.

Highlights

Overview: As previously described,[1] the collaborating cohorts were asked to compile a dataset with approximately 40 variables
For 21 of the 26 cohorts in this specific study of potassium, the Data Coordination Center at Johns Hopkins University conducted the analysis; the remainder ran the standard code written in STATA by the Data Coordinating Center and shared the output with the Data Coordinating Center
The Data Coordinating Center meta-analyzed the estimates across cohorts using STATA

Summary

Introduction

Overview: As previously described,[1] the collaborating cohorts were asked to compile a dataset with approximately 40 variables (key exposures [serum creatinine to estimate GFR, serum potassium and albuminuria], covariates [e.g., age, sex, race/ethnicity, diabetes, hypertension], and outcomes [event variables and corresponding follow-up times]). Geisinger: Due to the requirement of ACR measurement for analyses and the clinical indications that are associated with measurement in this health system dataset, this cohort was categorized as a high-risk cohort.

Results

Conclusion