Professor Sun Xuefeng: Medical and nursing co-management makes it no longer difficult to manage hyperkalemia in hemodialysis patients

Foreword: The number of patients with end-stage renal disease (ESRD) in China is huge, and by the end of 2022, the number of dialysis patients registered in Chinese mainland has exceeded 1 million [1]. Hyperkalemia is a common and serious complication in patients with ESRD, and retrospective observational studies of patients with chronic kidney disease (CKD) from 1971 to 2017 showed a prevalence of hyperkalemia (serum potassium > 5.5 mmol/L) in patients receiving hemodialysis or continuous ambulatory peritoneal dialysis was 16.4 and 10.6 percent, respectively [2]. Although some clinical studies in recent years have defined hyperkalemia as a serum potassium > 5.0 mmol/L, hyperkalemia is defined as a > 5.5 mmol/L of serum potassium.

Hyperkalaemia significantly increases the risk of death in dialysis patients, so intensive potassium management in dialysis patients is essential. However, potassium management in hemodialysis patients is a complex process that requires the collaboration of the care team. In this issue of China Medical Tribune, Professor Sun Xuefeng from the Department of Nephrology of the First Medical Center of the PLA General Hospital, analyzed the management of blood potassium in hemodialysis patients from the perspective of medical and nursing co-management.

Prof. Xuefeng Sun

• Chief physician, professor and doctoral supervisor of the PLA General Hospital
• Deputy Director of the Department of Nephrology of the General Hospital of the People's Liberation Army
• Chief Scientist of the National "973" Project
• Chairman of the Blood Purification Treatment and Engineering Technology Branch of the China Medical Promotion Association
• Chairman of the All-Army Blood Purification Therapeutics Professional Committee
• Vice Chairman of the Blood Purification Branch of Beijing Medical Association

Why are hemodialysis patients prone to hyperkalemia? What are the dangers of abnormal serum potassium?

Hemodialysis can effectively remove potassium ions from the patient's blood circulation and reduce blood potassium levels; However, potassium ions are mainly present in cells, so after hemodialysis, the patient's intracellular potassium ions are released into the systemic circulation, which can increase blood potassium again; In addition, the potassium absorbed from the diet is mainly excreted through the kidneys, which have a strong ability to excrete potassium, "eat more and excrete more, eat less and excrete less, and excrete without eating". Dialysis patients have severe impairment of potassium excretion due to renal failure, especially dialysis patients who have no urine and completely lose the ability of the kidneys to excrete potassium. As a result, potassium beyond what the body needs is often not excreted from diets after dialysis and on non-dialysis days, resulting in elevated serum potassium levels and hyperkalemia.

Of note, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) increase serum potassium by inhibiting distal tubular potassium secretion and excretion; However, in hemodialysis patients, particularly those with anuria, these drugs do not affect serum potassium levels due to loss of renal potassium excretion. A frequency random-effects network meta-analysis of 40 randomized controlled trials of 4283 patients on maintenance dialysis showed no significant difference in the risk of hyperkalemia due to ACEI INHIBITORS, ARB, MRA, α-blockers, β-blockers, and calcium channel blockers [3].

Potassium has important physiological functions, not only to maintain the body's acid-base balance, the body's nerves, muscle excitability and heart function, but also as an enzyme cofactor to participate in cell metabolism, and prevent and treat osteoporosis and kidney stones. In particular, serum potassium levels are important for maintaining normal heart rhythm and myocardial systolic function, and both hypokalemia and hyperkalemia can cause fatal arrhythmias and myocardial systolic dysfunction, leading to death. From 2007 to 2010, the annual cohort results of 28,774~36,888 hemodialysis patients showed that compared with patients with pre-dialysis potassium < 5.7 mmol/L, the all-cause mortality rate of patients with serum potassium ≥ 5.7 mmol/L increased by 13%, and that of patients with ≥ 6.0 mmol/L increased by 37%[4]. Analysis of data from 62,070 hemodialysis patients in 21 countries, phase 4-6 of the Dialysis Outcomes and Patterns of Practice Study (DOPPS) showed a 15 percent, 19 percent, and 33 percent increase in all-cause mortality in patients with peak potassium ≤ 5.0 mmol/L>, compared with patients with peak potassium 5.0 mmol/L, and 5.6 mmol/L [5]. On the other hand, a cohort study of 1117 hemodialysis patients showed a 42 percent increased risk of death in patients with a predialysis potassium ≤ 4.0 mmol/L [6].

Is dietary control effective in lowering blood potassium?

Increasing potassium intake in the general population can reduce the incidence of cardiovascular and cerebrovascular diseases. However, as mentioned earlier, dialysis patients often develop hyperkalemia due to loss of renal potassium excretion, increasing the risk of malignant arrhythmias and sudden death. Therefore, hemodialysis patients are often recommended to reduce their dietary potassium intake and limit their intake of potassium-rich fruits and vegetables to prevent hyperkalemia. However, there is no consistent conclusion on the relationship between dietary potassium intake and serum potassium and survival in hemodialysis patients [7]. The results of the prospective cohort of 8043 patients on maintenance hemodialysis who followed up for 4 years showed that dietary potassium intake was not significantly associated with all-cause mortality, and there was no significant correlation between potassium intake and serum potassium level or prevalence of hyperkalemia at the beginning of the study. However, hyperkalemia increases the risk of cardiovascular mortality by 23 percent [8]. Therefore, dietary potassium restriction alone is not effective in controlling serum potassium levels in hemodialysis patients, nor does it reduce the risk of death.

How can I safely lower my blood potassium with hemodialysis?

During hemodialysis, the serum-dialysate potassium gradient is used to achieve the diffusion of potassium ions from the blood to the dialysate, and the potassium ions in the blood circulation are removed. Therefore, the larger the serum-dialysate potassium gradient, the more potassium ions are cleared. However, the results of a retrospective cohort study of Medicare-covered hemodialysis patients in the United States Kidney Data System from 2007 to 2017 showed that the serum-dialysate potassium gradient was ≥ 3 mmol/L< 3 mmol/L is associated with a 122 percent increased risk of sudden cardiac death [9]. In a prospective observational cohort study of 600 hemodialysis patients in a multicenter in China, 16.9 percent had hyperkalemia, 97.9 percent received dialysate with a potassium concentration of 2.0 mEq/L, and more than 40 percent had a serum-dialysate potassium gradient of >3 mmol/L [10]. Therefore, for patients with pre-dialysis hyperkalemia, dialysate with a potassium concentration of 3.0 mmol/L should be used, and the dialysis duration should be increased appropriately if necessary to safely and effectively reduce the serum potassium level. In addition, because potassium retention after dialysis can lead to hyperkalemia before the next dialysis, it is also possible to reduce the serum potassium gradient by taking potassium-lowering drugs to reduce the serum potassium gradient before the next dialysate.

How to choose and use potassium-lowering drugs?

The potassium concentration of dialysate has a very low effect on serum potassium before the next dialysis, and the analysis results of 55,183 hemodialysis patients in the phase 1-5 DOPPS study showed that each increase in dialysate potassium concentration of 1.0 mmol/L only increased the serum potassium before the next dialysis by 0.09 (95%CI: 0.05~0.14) mmol/L [11]. However, potassium-lowering drugs can be effective in lowering serum potassium levels in patients with CKD and hemodialysis. Systematic reviews and meta-analyses of 1849 patients with CKD and hemodialysis taking potassium-lowering drugs (including calcium polystyrene sulfonate, sodium polystyrene sulfonate, sodium zirconium cyclosilicate, and Patiromer) showed that potassium-lowering drugs significantly reduced serum potassium levels in patients with CKD and HD compared with placebo, with no significant difference in nausea, diarrhea, vomiting, and constipation in patients with CKD [12]. Therefore, potassium-lowering drugs can be used to control serum potassium levels safely and effectively in patients with frequent elevated serum potassium.

The ideal control of potassium-lowering drugs in hemodialysis patients not only needs to have the characteristics of low price, easy to use and good tolerance, but also should have fast-onset but slow and continuous potassium-lowering efficacy. In order to effectively control serum potassium on non-dialysis days and before the next dialysis, without causing rapid fluctuations in serum potassium and the occurrence of hypokalemia.

At present, there are three potassium-lowering drugs that can be clinically obtained in China: (1) sodium polystyrene sulfonate mainly acts on the colon, non-selectively combines potassium, calcium and magnesium, and takes effect in 2~6 hours, and the adverse reactions are gastrointestinal symptoms, edema, hypokalemia, etc.; (2) Calcium polystyrene sulfonate also acts on the colon, non-selectively binding potassium and magnesium, the onset time is uncertain, and the adverse reactions are constipation, intestinal perforation, intestinal obstruction, hypokalemia, etc.; (3) The new oral potassium ion exchanger acts on the whole digestive tract, is highly selective in combination with potassium ions, and takes effect within 1 hour, and the main adverse reactions are edema and hypokalemia. However, none of the three potassium-lowering drugs fully possess the characteristics of the ideal potassium-lowering drugs.

Interestingly, in the results of systematic reviews and meta-analyses of CKD and hemodialysis patients taking potassium-lowering drugs, potassium-lowering drugs significantly reduced serum potassium, systolic blood pressure, and diastolic blood pressure, but sodium zirconium cyclosilicate and Patiromer had no significant effect on all-cause mortality, cardiovascular death, and quality of life, while calcium polystyrene sulfonate and sodium polystyrene sulfonate lacked relevant data [12]. Zirconium cyclosilicate and Patiromer effectively reduce serum potassium but do not improve the risk of death, and the possible factors are: (1) excessive reduction of serum potassium; (2) Cause excessive fluctuations in blood potassium. In a cohort study of 1117 hemodialysis patients, patients with a predialysis potassium ≤ 4.0 mmol/L had a 42 percent increased risk of death [6]. The results of a retrospective study of 357 peritoneal dialysis patients showed that the survival rate of patients with a time mean serum potassium > 4.0 mmol/L was significantly reduced compared with patients with a time mean serum potassium ≤ 4.0 mmol/L. For patients with a time-mean serum potassium > 4.0 mmol/L, all-cause or cardiovascular survival was significantly reduced with a standard deviation of <0.54 mmol/L ≥ 0.54 mmol/L [13]. Therefore, safe and effective potassium lowering should avoid excessive potassium reduction and excessive potassium fluctuations.

Sodium zirconium cyclosilicate has a fast onset of action, but it decreases potassium rapidly, which is easy to cause excessive reduction and fluctuation of serum potassium. To solve this problem, efforts need to be made to manage patients.

(1) For patients on maintenance hemodialysis, pre-dialysis, post-dialysis and non-dialysis daily serum potassium should be tested, and the patient's serum potassium status should be completely assessed; For patients with pre-dialysis and/or non-dialysis daily potassium > 5.0 mmol/L, the frequency of serum potassium monitoring should be increased appropriately.

(2) Medical staff, especially dialysis nurses, should teach patients how to identify potassium-rich foods and appropriately reduce the intake of potassium-rich foods.

(3) Patients should be taught how to reduce potassium content in food through cooking. Potassium is mainly found in cells, and potassium can be removed by breaking the cell wall of the food by cutting it into thin strips, and then removing the potassium from the food by continuous water rinsing or boiling.

(4) Patients should be taught to take potassium-lowering drugs correctly. Oral potassium-lowering drugs mainly reduce potassium absorption and eliminate potassium through the intestine by adsorbing or replacing potassium ions in food/intestinal fluid. If potassium-lowering drugs are taken on an empty stomach, they can cause a rapid decrease in serum potassium; If potassium-lowering drugs are not taken at the same time as foods that contain more potassium, potassium absorption is not effective in reducing potassium absorption, resulting in an increase in serum potassium. Therefore, health care providers should first help patients determine the possible potassium content in the three meals, and then give different doses of potassium-lowering drugs according to the potassium content of each of the three meals, mixed with food. Regular doses of potassium-lowering drugs taken orally 2 times a day or 3 times a day will inevitably lead to excessive potassium lowering at times and insufficient potassium lowering at times, resulting in potassium fluctuations or short-term hypokalemia and increasing the risk of death. However, unfortunately, most of the current clinical use of this potassium-lowering drug is taken.

In short, hyperkalemia is a common and harmful complication in hemodialysis patients, and dietary control alone cannot effectively prevent and treat hyperkalemia. In addition, the development of ideal potassium-lowering drugs and further clinical evidence-based medical research to confirm effective potassium-lowering treatment regimens are scientific issues that need to be solved in the future.

bibliography

1. Chen Xiangmei, 2023 Academic Annual Meeting of Nephrology Branch of Chinese Medical Doctor Association.

2.Belmar Vega L, Galabia ER, Bada da Silva J, et al. Epidemiology of hyperkalemia in chronic kidney disease. Nefrologia (Engl Ed), 2019, 39(3):277-286.

3.Shaman AM, Smyth B, Arnott C, et al. Comparative Efficacy and Safety of BP-Lowering Pharmacotherapy in Patients Undergoing Maintenance Dialysis: A Network Meta-Analysis of Randomized, Controlled Trials. Clin J Am Soc Nephrol, 2020, 15(8):1129-1138.

4.Yusuf AA, Hu Y, Singh B, Menoyo JA, et al. Serum Potassium Levels and Mortality in Hemodialysis Patients: A Retrospective Cohort Study. Am J Nephrol, 2016, 44(3):179-186.

5.Karaboyas A, Robinson BM, James G, et al. Hyperkalemia excursions are associated with an increased risk of mortality and hospitalizations in hemodialysis patients. Clin Kidney J, 2020, 14(7):1760-1769.

6.de Rooij ENM, Dekker FW, Le Cessie S, et al. Serum Potassium and Mortality Risk in Hemodialysis Patients: A Cohort Study. Kidney Med, 2021, 4(1):100379.

7.Sun Z, Jiao J, Lu G, et al. Overview of research progress on the association of dietary potassium intake with serum potassium and survival in hemodialysis patients, does dietary potassium restriction really benefit hemodialysis patients? Front Endocrinol (Lausanne), 2023, 14:1285929.

8.Bernier-Jean A, Wong G, Saglimbene V, et al. Dietary Potassium Intake and All-Cause Mortality in Adults Treated with Hemodialysis. Clin J Am Soc Nephrol, 2021, 16(12):1851-1861.

9.Pun PH, Assimon MM, Wang L, et al. QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis. Kidney Med, 2023, 5(5):100618.

10.Ni Z, Jin H, Lu R, et al. Hyperkalaemia prevalence and dialysis patterns in Chinese patients on haemodialysis: an interim analysis of a prospective cohort study (PRECEDE-K). BMC Nephrol, 2023, 24(1):233.

11.Karaboyas A, Zee J, Brunelli SM, et al. Dialysate Potassium, Serum Potassium, Mortality, and Arrhythmia Events in Hemodialysis: Results From the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis, 2017, 69(2):266-277.

12.Natale P, Palmer SC, Ruospo M, et al. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev, 2020, 6(6): CD013165.

13.Li SH, Xie JT, Long HB, et al. Time-averaged serum potassium levels and its fluctuation associate with 5-year survival of peritoneal dialysis patients: two-center based study. Sci Rep. 2015 Oct 28;5:15743.

Disclaimer: For the information of healthcare professionals only, not to be forwarded or shared by non-healthcare professionals. Not to be used for promotional purposes. This article was written/published with support from AstraZeneca.

Approval Number: CN-140140 Expiration Date: 2025-1-28