CHICAGO—Patients with abnormally low or high serum potassium levels have significantly greater risks of end-stage renal disease (ESRD) and premature death, researchers reported at the American Society of Nephrology’s Kidney Week 2016 meeting.  

For the CKD Prognosis Consortium, Csaba P. Kovesdy MD, chief of nephrology at the Memphis VA Medical Center and The Fred Hatch Professor of Medicine at the University of Tennessee Health Science Center in Memphis, and colleagues examined serum potassium values across 26 diverse, international cohorts: 15 general populations, 9 chronic kidney disease (CKD) populations, and 2 populations at high cardiovascular risk. Among 1,538,508 participants (average age 52, 42% female, and 14% black), average serum potassium level at baseline was 4.3 mmol/L. Average estimated glomerular filtration rate (eGFR) was 84 mL/min/1.73 m2. Overall, 14% had albuminuria, and 38% took antihypertensive medications.

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Meta-analyses revealed increased risks of all-cause mortality for participants with potassium values below 3.5 or above 5 mmol/L, over an average 7 years of follow up. The lowest risk category was 4 to 4.5 mmol/L, within the center of the normal range.                                                         

Compared to a reference of 4.2 mmol/L, the odds for all-cause mortality were 22% higher at 5.5 mmol/L and 31% higher at 3.2 mmol/L. Similar risks were observed for cardiovascular mortality and ESRD. The investigators adjusted for a range of demographic and clinical variables, including age, sex, race, diabetes, systolic blood pressure, antihypertensive medications, cardiovascular disease, heart failure, total cholesterol, body-mass index, smoking, eGFR, and albuminuria. The risks were similar regardless of degree of albuminuria and treatment with inhibitors of the renin–angiotensin–aldosterone system.

When the researchers tested for interactions between eGFR and potassium, the association of potassium with low eGFR below 30 mL/min/1.73 m2 slightly weakened in the case of ESRD only.

“The association between hypo- and hyperkalemia and mortality could be explained by the induction of malignant arrhythmias and their consequences, such as hypotension, myocardial ischemia and sudden cardiac death, although the present analyses cannot elucidate the direct causal role of abnormal potassium in the observed outcomes,” Dr Kovesdy told Renal & Urology News.

The relationship, if any, between abnormal potassium levels and ESRD is less clear. Hypokalemia could lead to tubulointerstitial fibrosis, according to the investigators. Hyperkalemia simply may serve as a marker of more severe CKD or it may indirectly harm kidney function, such as following cardiac events.

Dr Kovesdy and his colleagues encouraged future randomized controlled clinical trials to ascertain whether correcting abnormal levels of the electrolyte reduces the chances of ESRD and early death.

The CKD Prognosis Consortium Data Coordinating Center is funded in part by grants from the US National Kidney Foundation, which sponsors include Relypsa, and the National Institute of Diabetes and Digestive and Kidney Diseases.

Click here for more coverage from the American Society of Nephrology’s Kidney Week 2016 in Chicago.

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1. Kovesdy CP, Matsushita K, Sang Y, et al. Serum Potassium and the Risk of Adverse Outcomes: A CKD Prognosis Consortium Meta-Analysis. Presented at: Kidney Week 2016. November 15-20, 2016. Chicago. Abstract TH-PO475.