Journal of Renal and Hepatic Disorders 2018; 2(2): 6–9 6 REVIEW ARTICLE Potassium Profiling in Hemodialysis Nikhil Agrawal1, Sahil Agrawal2, Nishita Tripathi3, Mark Segal4 1Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA, USA; 2Cardiology, St Luke’s Hospital, Allentown, PA, USA; 3Medicine, Kempegowda Institute of Medical Sciences, Bangalore, Karnataka, India; 4Nephrology, University of Florida, Gainesville, FL, USA Abstract Cardiac dysrhythmia and sudden death account for a large proportion of cardiac mortality in dialysis patients. Risk factors for sudden death that are specific to dialysis patients include fluid and electrolyte imbalances during hemodialysis, particularly those of potassium. The risk of arrhythmia may be related to changes in serum K+ concentration during dialysis, and thus close attention should be paid to the dialysate K+ concentration and the serum–dialysate concentration gradient. Potassium profiling is a technique where the dialysate K+ concentration is gradually reduced to keep the gradient between blood and dialysate at a non-fluctuating low level. We provide a review of studies that compare constant potassium concentration in dialysate to gradual reduction in dialysate potassium concentration. These studies illustrate that adequate and more gradual potassium removal can be achieved with potassium profiling techniques, while having lower cardiac irritability. Keywords: arrhythmia; dialysate potassium; potassium profiling; potassium removal; sudden cardiac death Received: 30 May 2018; Accepted after Revision: 19 July 2018; Published: 07 August 2018 Author for correspondence: Nikhil Agrawal, Division of Nephrology, Beth Israel Deaconess Medical Center, 185 Pilgrim Road, Boston, MA 02215, USA. Email: nagrawa2@bidmc.harvard.edu How to cite: Agrawal N et al. Potassium profiling in hemodialysis. J Ren Hepat Disord. 2018;2(2):6–9 Doi: http://dx.doi.org/10.15586/jrenhep.2018.34 Copyright: Agrawal N et al. License: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0 Introduction Mortality and morbidity in End Stage Renal Disease (ESRD) patients on hemodialysis (HD) remains high, and higher than non-dialysis patients with similar co-morbidity burden (1). Cardiac dysrhythmia and sudden death account for a large proportion of cardiac mortality in these patients, amounting to 26.9% of total deaths (1). Risk factors for sud- den death that are specific to dialysis patients include fluid and electrolyte imbalances during HD, particularly those of potassium(K+) (2). Most of the evidence linking the risk of arrhythmia to dialysis is derived from Electrocardiogram (EKG) markers such as ventricular repolarization indices which include QT duration (QTc), QT dispersion (QTd), PCA-T (principal component analysis of T wave), and E1-T (first eigenvalue of T wave) (3–11). These indices are known to reflect increased risk of arrhythmia (11, 12) and one of the factors which has been shown to change these indices is the change in serum potassium, stemming from the critical role of the K+ ion in myocardial repolarization (6, 13–15). Both hypokalemia and hyperkalemia have been shown to have associations with higher mortality in HD pa- tients (16). Due to lack of renal function to handle potassium excretion, ESRD patients undergo potassium removal dur- ing dialysis. In HD, this is achieved by diffusion of potassium from a higher concentration in serum to lower concentration codonpublications.comjrenhep.com mailto:nagrawa2@bidmc.harvard.edu http://dx.doi.org/10.15586/jrenhep.2018.34 http://creativecommons.org/licenses/by/4.0 Potassium profiling in hemodialysis Journal of Renal and Hepatic Disorders 2018; 2(2): 6–9 7 in dialysate, and is thus directly proportional to the concen- tration gradient between blood and dialysate. Hyperkalemia is associated with higher mortality in dialysis patients (16) and high potassium concentration in dialysate might impair potassium removal. But at the same time, multiple studies have associated low dialysate potassium with higher risk of sudden cardiac death. It was noted in a study with the dialy- sate K+ concentration of 0 and 1 meq/L (17), and with dial- ysate K+ of less than 3 (18). Further, another study showed less arrhythmia when the K+ bath was 3.5 versus 2 (19). This may be related to rapid changes in serum potassium during dialysis, and the challenge is to balance adequate potassium removal with risk of arrhythmia while doing it. Potassium profiling is a technique where the dialysate K+ concentration is gradually reduced to limit the gradi- ent between blood and dialysate constant and low. It has the potential advantage of reducing rapid changes in serum potassium level during dialysis (and thus reducing cardiac irritability), while also allowing for adequate potassium removal. Here we provide a review of the randomized control tri- als that have compared potassium profiling of dialysate to a fixed dialysate potassium concentration. Methods We searched the PubMed database using search terms “po- tassium profiling,” “potassium profiling in hemodialysis,” “potassium hemodialysis,” and “dialysate potassium.” We included only the randomized control trials done in the past 25 years. The first study in our literature review to employ this technique was published in 1990 by Ebel et al. (20). Using a computerized program, they removed K+ slowly at a rate of 15%/hour and showed that incidence of arrhythmia was reduced from 60 to 25% (20). Since then, multiple randomized control trials have looked at potas- sium profiling. Although they have used different profil- ing techniques, all these studies have looked at effects of potassium profiling on cardiac stability using electrocar- diographic markers and also ability to effectively remove potassium during dialysis. Results A brief overview of these studies is provided in Table 1 (21–26). All studies included in our review used a cross over design to compare constant potassium concentration in di- alysate to gradual reduction in dialysate potassium concen- tration. The number of subjects was small, ranging from 10 to 36 patients. Inclusion and exclusion criteria were variable; some studies excluded patients with significant cardiovascu- lar disease (3, 4), while others included only those who were considered high risk for arrhythmias (1, 6, 7). Although none of these studies looked exclusively at hyperkalemic patients, the average serum K+ concentration in these studies was nor- mal or slightly high (up to 6 meq/L) and two studies excluded patients with hypokalemia (2, 6). The dialysate potassium in control patients was mostly 2 meq/L. The potassium profiling techniques used in study  population varied in different studies and are listed in Table 1. A limitation of these studies is that arrhythmic risk using indirect EKG and Holter markers was assessed rather than actual arrhythmia events. This relates to the rather small number of study subjects and therefore the low overall inci- dence of arrhythmia. In the absence of a unanimous EKG marker for predicting arrhythmia with changes in K+, in- direct measures of cardiac excitability and ventricular re- polarization including Premature Ventricular Contractions (PVCs), changes in QTc/QTd/PCA-T/E1-T were used as surrogate markers of arrhythmic risk. Lower cardiac irrita- bility with potassium profiling was shown in all studies. The effects were generally more pronounced in patients who are at higher risk of arrhythmia or who are dialysis sensitive. Comparison of potassium removal with standard versus potassium profiled dialysate techniques was done by mea- suring post-HD or pre-HD (prior to next session) serum potassium concentrations. There was no significant differ- ence in these levels between the two techniques. Further, the training and technical requirements to implement this tech- nique in a HD unit did not increase the work load of the nephrologist or the nurses, nor did it increase the technical complexity (27). Conclusion There are no standard practices for dialysate potassium concentrations and no recommendation has been provided in the NKF-KDOQI (National Kidney Foundation–Kid- ney Disease Outcomes Quality Initiative) cardiovascular disease guideline. In a large international cohort of HD patients, dialysate potassium concentration varied among clinical practices and countries and ranged anywhere from 1 meq/L to 3 meq/L (28). There are no large studies show- ing a difference in clinically significant arrhythmic events when gradually removing potassium in dialysis patients via potassium profiling of dialysate. However, there are mul- tiple small studies suggesting a lower risk of arrhythmia with potassium profiling by using indirect markers of car- diac excitability and ventricular repolarization. Also, these studies suggest that an adequate amount of potassium could be removed without having a high gradient, at no extra financial cost. 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