posted on 2019-08-15, 11:02authored byCP Kovesdy, K Matsushita, Y Sang, NJ Brunskill, JJ Carrero, G Chodick, T Hasegawa, HL Heerspink, A Hirayama, GWD Landman, A Levin, D Nitsch, DC Wheeler, J Coresh, SI Hallan, V Shalev, ME Grams, CKD Prognosis Consortium
Aims: 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. Methods and results: 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 1 217 986 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. Conclusions: Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.
Funding
The CKD-PC Data Coordinating Center is funded in part by a programme grant from the US National Kidney Foundation (NKF funding sources include Relypsa) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100446-01). A variety of sources have supported enrolment and data collection including laboratory measurements and follow-up in the collaborating cohorts of the CKD-PC. These funding sources include government agencies such as national institutes of health and medical research councils as well as foundations and industry sponsors listed in Supplementary material online, Appendix S3. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
History
Citation
European Heart Journal, 2018, 39 (17), pp. 1535-1542
Author affiliation
/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation
Version
AM (Accepted Manuscript)
Published in
European Heart Journal
Publisher
Oxford University Press (OUP) for European Society of Cardiology