Blog entry by Meguid El Nahas
Serum Potassium Levels and Mortality in Hemodialysis Patients: A Retrospective Cohort Study
Hyperkalemia is common in patients receiving maintenance hemodialysis. However, few studies have examined the association between serum potassium level and mortality.
This study used annual cohorts of hemodialysis patients during 2007-2010. To determine hyperkalemia prevalence, monthly hyperkalemia was defined as serum potassium level ≥5.5 mEq/l; prevalence was calculated as a ratio of hyperkalemia episodes to follow-up time, reported separately by long and short interdialytic interval. To determine the impact of hyperkalemia on mortality, patients in the 2010 cohort were followed from first potassium measurement until death or a censoring event; hyperkalemia was defined, sequentially, by potassium levels 5.5-6.0 mEq/l at 0.1 mEq/l intervals. Time-dependent Cox proportional hazards modeling was used to estimate the association between hyperkalemia and mortality.
The 4 annual cohorts ranged from 28,774 to 36,888 patients. Mean age was approximately 63 years, about 56% were men, 51% were white and 44% had end-stage renal disease caused by diabetes. Hyperkalemia prevalence was consistently estimated at 16.3-16.8 events per 100 patient-months. Prevalence on the day after the long interdialytic interval was 2.0-2.4 times as high as on the day after the short interval. Hyperkalemia, when defined as serum potassium ≥5.7 mEq/l, was associated with all-cause mortality (adjusted hazards ratio (AHR) 1.13, 95% CI 1.01-1.28, p = 0.037, vs. <5.7 mEq/l) after adjustment. AHRs increased progressively as the hyperkalemia threshold increased, reaching 1.37 (95% CI 1.16-1.62, p < 0.0001) for ≥6.0 mEq/l.
The long interdialytic interval was associated with increased likelihood of hyperkalemia. Hyperkalemia was associated with all-cause mortality beginning at serum potassium ≥5.7 mEq/l; mortality risk estimates increased ordinally through ≥6.0 mEq/l, suggesting a threshold at which serum potassium becomes substantially more dangerous.
© 2016 S. Karger AG, Basel.
Commentary by Prof Richard Glassock
Hyperkalemia is a common and potentially life-endangering complication of CKD, especially in the very advanced forms of CKD. The risk of an adverse event, including death, arising from hyperkalemia is thought to be related to the magnitude of the increase in serum level of potassium (K+) above the normal ranges, but the exact relationship between the serum level of K+ and mortality is not well known, and probably is influenced be many factors.
Yusuf and co-workers carried out a retrospective cohort study over the period of 2007-2010 in 135,021 prevalent patients receiving hemodialysis for treatment for ESRD, in order to better establish risks of mortality in patients with hyperkalemia of varying severity. About 60% had diabetes and 38% had congestive heart failure. The dialysate potassium was 2-<3mmol/L in 67-77% of the cohorts. Hyperkalemia was estimated to occur in 16 episodes per 100 patient months, much higher on the day after the longest inter-dialytic interval. The use of sodium polystyrene sulfate was not recorded.
The all-cause mortality (ACM) rate increased incrementally as serum K+ rose above 5.7mmol/L. The fully- adjusted hazard ratio (HR) for ACM for subjects with a serum K+ of >6.0mmol/L was 1.37 compared to that observed in subjects with a serum K of 5.5mmol/L or less. The impact of hypokalemia on ACM was not examined. The fully-adjuster HR for CKD mortality was only increased above a serum K+ of 6.0mmol/L.
The data used in this study was collected before new K+ binding resins became available (patiromer), so the rate of hyperkalemia and its consequences may not be directly relevant to contemporary treatment of ESRD by hemodialysis, but the relationship of serum K+ to mortality risk probably still holds true. Interestingly, hyperkalemia was more frequent in Caucasian and younger subjects - the explanation for this finding is uncertain but might relate to dietary factors, concomitant medications or underlying disease. More studies are needed to better define the risks of hyperkalemia and its consequence according to co-morbidities. Most importantly randomized controlled trials using modern oral K+ binding agents with objective hard outcomes are needed to determine be how the adverse effects of hyperkalemia in ESRD can be modified by such agents and which patients would be ideally suited for such therapy. These findings suggest that short-term (1-2 days) days of therapy during the longest inter-dialytic interval might be a good target.