Patients with advanced chronic kidney disease (CKD) are at higher risk of hospitalization or requiring an emergency room (ER) visit in the short-term if they have abnormal potassium levels, a nationally representative cohort of US veterans with advanced CKD indicates. The risk was especially high for those with hyperkalemia.
Most prior studies have looked at long-term associations between abnormal potassium levels and clinical outcomes, “but biologically…abnormal potassium’s effect on an outcome is instantaneous,” senior author Csaba Kovesdy, MD, professor of medicine, University of Tennessee Health Science Center, Memphis, told Medscape Medical News.
“The reason this is more relevant these days is because we have better tools to prevent the development of hyperkalemia [in particular],” he noted. “Establishing these associations is an important step forward in reaching the point where we can actually intervene to prevent these outcomes.”
Asked by Medscape Medical News for comment, Manish Sood, MD, agreed that although observational, the study is nevertheless worthwhile.
The next important step will be to conduct a study that looks at causality — whether newer potassium-binding drugs do impact outcomes. “If you put these patients on these newer potassium binders, you could then look and see how many patients are…admitted for hyperkalemia,” explained Sood, associate professor of medicine, University of Ottawa, Ontario, Canada.
Two new potassium-binding agents have been approved by the US Food and Drug Administration over the past 5 to 7 years for the treatment of hyperkalemia: patiromer (Veltassa, Vifor Pharma) and sodium zirconium cyclosilicate (Lokelma, AstraZeneca).
Study Looked at Patients Transitioning to Dialysis
Advanced CKD is the single biggest risk factor for potassium abnormalities because of the role the kidney plays in eliminating potassium, Sood explained. Plus, many of the medications taken by patients with CKD can affect potassium levels, and renin-angiotensin system (RAS) inhibitors and diuretics are two such culprits. Hyperkalemia can put patients at risk for cardiac arrhythmias, and with hypokalemia, patients can feel muscle weakness and even muscle paralysis, Sood noted.
The aim of the study, which was published by Ankur A. Dashputre, also of the University of Tennessee Health Science Center, and colleagues in the Journal of Managed Care & Specialty Pharmacy, was to assess the association of dyskalemia with short-term hospital/ER visits in patients with CKD transitioning to dialysis.
Among 102,477 US veterans in 2007-2015, researchers identified 21,366 patients with two predialysis outpatient estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73m2 taken 90-365 days apart (with the second eGFR serving as the index date) and at least one potassium level in the baseline period (1 year before index) and 1 outpatient potassium level during follow-up (1 year after the index date but before dialysis initiation).
They examined the association of time-varying hypokalemia (potassium < 3.5 mEq/L) and hyperkalemia (potassium > 5.5 mEq/L) versus referent values (potassium 3.5-5.5 mEq/L) with separate hospital and ER visits within 2 calendar days following each outpatient potassium value over the 1-year follow-up period from the index start date.
The mean age of patients was 68.6 years, almost all were men, and almost three quarters were taking a RAS inhibitor. Over two thirds were taking a beta blocker and a similar percentage were taking a calcium channel blocker. The median index eGFR was 24.8 mL/min/L.173 m2. Patients had a median of three potassium measurements, with a mean potassium level of 4.5 mEq/L at baseline.
“At least one hyperkalemia and hypokalemia event [at] baseline was experienced by 17.3% and 11.3% [of the cohort], respectively,” the authors note.
Over the subsequent year of follow-up, 40% of patients had a hospital visit and 6.8% of hospital visits were observed within 2 days of the measured outpatient potassium level.
Hyperkalemia was associated with a twofold higher risk of needing a hospital visit and hypokalemia was associated with a 66% higher risk of needing a hospital visit, at an odds ratio of 2.04 and 1.66, respectively, after multivariable adjustment.
“Among the 8542 hospital visits, 36% were due to ‘diseases of the circulatory system’ (of which 5.6% were due to ‘arrhythmias’),” the authors observe.
Risk for Short-Term Visits Highest at Extreme Potassium Levels
Over the year’s follow-up from the start date, one third of patients experienced an ER visit.
Across all outpatient potassium measurements during that follow-up period, 4.1% of ER visits were observed within 2 days of that potassium measurement.
In the multivariable-adjusted model, hyperkalemia was associated with an almost twofold higher risk of an ER visit and hypokalemia was associated with a 24% higher risk of an ER visit, the investigators noted.
“Overall, the risk for such short-term visits was higher following a hyperkalemia event compared with a hypokalemia event…and the risk for short-term visits was highest at the extreme potassium levels,” the authors summarize.
“Close monitoring of potassium levels and the advent of newer potassium-binding agents (in the context of hyperkalemia) might help in reducing healthcare utilization and eventual economic burden,” they conclude.
The study was supported by a grant from the National Institutes of Health. Kovesdy has reported receiving honoraria from Akebia, Ardelyx, AstraZeneca, Bayer, Boehringer-Ingelheim, Cara Therapeutics, Reata, and Tricida. Sood has reported receiving speakers fees from AstraZeneca.
J Manag Care Spec Pharm. 2021;27:1403-15. Full text
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