Chronic Hyperkalaemia with Patiromer in Haemodialysis: A Single-Center, Prospective Observational Study in the Clinical Practice

Special Article: Dialysis

Austin J Urol. 2023; 9(1): 1079.

Chronic Hyperkalaemia with Patiromer in Haemodialysis: A Single-Center, Prospective Observational Study in the Clinical Practice

Vicent Esteve Simó*; Irati Tapia González; Ursula Vadillo Vidal; Claudia Guzmán Rubiano; Fátima Moreno Guzmán; Diana Oleas Vega; Verónica Duarte Gallego; Mónica Pou Potau; Anna Saurina Solé; Manel Ramírez de Arellano Serna

Department of Nephrology, Hospital de Terrassa Consorci Sanitari Terrassa (CST), Barcelona, Spain

*Corresponding author: Vicent Esteve Simó Department of Nephrology, Hospital de Terrassa. Consorci Sanitari Terrassa (CST), Crta Torrebonica s/n 08227 Terrassa (BCN), Barcelona, Spain. Tel: +34937310007 Email: vesteve@cst.cat

Received: August 18, 2023 Accepted: September 30, 2023 Published: October 07, 2023

Abstract

Introduction: Chronic Kidney Disease (CKD) patients on Hemodialysis (HD) experience increased risk of hyperkalemia, a serious potential fatal electrolyte disorder. Although novel effective strategies for managing hyperkalaemia are available, experience in routine clinical practice is still insufficient. Here we report chronic hyperkalemia prevalence and analyze the effects of different treatments on potassium management, adherence ratio and gastrointestinal symptoms in HD population.

Methods: 12-week, prospective, single-center study in HD patients with chronic hyperkalaemia (>5.5 mmol/l). Three study phases were established: Phase 1, Dietary Advice (DA); Phase 2, Calcium Polystyrene Sulfonate Resins (CPSRs); and Phase 3, patiromer. Sociodemographic and biochemical data, treatment adherence and compliance (Simplified Medication Adherence Questionnaire), gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale, GSRS), HD characteristics and usual medical treatment were analyzed in each phase.

Results: Serum potassium values decreased significantly (p<0.05) only in phase 3 (–0.75 mmol/l), with a higher patient percentage reaching optimal K range. Compared with CPSRs, patiromer yielded significantly better overall GSRS scores: abdominal pain (3.7 versus 2.5), constipation (7.1 versus 5.3), indigestion (6.2 versus 5.6); and better treatment compliance. No significant changes were found in other biochemical data, HD characteristics or usual medication over the course of the study.

Conclusions: Chronic hyperkalemia is a highly prevalent disorder on our HD unit. Compared to DA and traditional potassium binders; patiromer was effective in managing chronic hyperkalemia, improving gastrointestinal symptoms and treatment adherence with no associated severe adverse effects. Therefore, patiromer can be considered a first-line treatment for chronic hyperkalemia in patients with HD.

Keywords: Chronic hyperkalemia; Hemodialysis; Patiromer; Potassium binding polymer; Efficacy

Introduction

Hyperkalemia is an electrolyte disturbance characterized by elevated serum potassium levels to values greater than 5 mmol/l [1,2]. Several homeostatic mechanisms keep extracellular potassium concentrations in a narrow physiologic range that simultaneously control both internal potassium redistribution and excretion. The first one is caused by the directional effects of acidemia and alkalemia between the intracellular and extracellular compartments [3]. Conversely, potassium is passively secreted into the lumen of the distal nephron in a process dependent of the concentration gradient across the luminal membrane, the lumen negative electrical gradient, and permeability of the luminal membrane to potassium [1]. When either or both processes are disturbed, a rise of extracellular potassium concentration is developed, which leads to hyperkalemia. While this condition is usually linked to the appearance of potentially fatal cardiac dysrhythmia, there are other severe consequences such as peripheral neuropathy, renal tubular acidosis or even death [4]. A retrospective cohort study of hemodialysis patients reported that the prevalence of hyperkalemia (=5.5 mEq/L) was 16.3 to 16.8 events per 100-patient months with the risk being approximately twice after the long interdialytic interval [5]. Indeed, significant alterations in potassium levels are common among patients undergoing hemodialysis, making it a well-documented condition [6]. In addition, an increased frequency has been observed among patients with Chronic Kidney Disease (CKD), diabetes, heart failure, and prescribed with certain medications like Renin Angiotensin Aldosterone System (RAAS) inhibitors and Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) [7-9].

Treatment of chronic hyperkalemia is focused on the identification and correction of the disturbances in potassium homeostasis, starting with the removal of high potassium intake diet, hyperkalemia-inducing therapies, or metabolic acidosis [10]. Nevertheless, these interventions are not usually effective to treat the condition, so treatment with potassium binding resins such as sodium-polystyrene sulfonate or calcium polystyrene sulfonate are usually initiated. However, concerns about their effectiveness and safety have arisen, due to the treatment efficacy being attributed to the co-administered sorbitol or the appearance of severe gastrointestinal injuries [11,12]. Despite this, the use of these compounds is widely common due to the lack of alternatives [13]. Nonetheless, during the last years, a novel non-absorbable polymer which binds potassium in exchange for calcium, patiromer, has demonstrated its efficacy in several studies as an alternative for the treatment of chronic hyperkalemia [14-18]. However, until date, there are currently no published studies about the use of novel potassium binders such as patiromer in the management of chronic hyperkalemia in hemodialysis patients in daily clinical practice.

The aim of this study was to report the prevalence of chronic hyperkalemia and analyze the effects of different treatment strategies on potassium management in clinical practice, ratio of adherence and gastrointestinal symptoms in our HD population.

Materials and Methods

Study Design

This was a single-center, prospective, observational study that included patients with hyperkalemia (>5.5 mEq/l) on a periodic hemodialysis program from of our hospital, approved by the Ethics Committee of the Consorci Sanitari de Terrassa (Barcelona, Spain) and conducted in accordance with the standards of the Helsinki Declaration. This trial consisted of three phases spanned over a 12-week period, with duration of three weeks for each one and a one-week bleaching period between the different stages. Three study phases were established: phase 1, Dietary Advice (DA); phase 2, calcium polystyrene sulfonate resins (CPSRs); and phase 3, patiromer. During the second and third phases, participants were administered 15g CPSR (Resincalcio®) every eight hours and 8.4g patiromer (Veltassa®) every 24 hours, respectively, in line with the approved posology.

The inclusion criteria were HD patients with proven hyperkalemia (>5.5 mEq/l potassium) after two consecutive measurements, treated with Renin-Angiotensin-Aldosterone System Inhibitors (RAASi) according to their clinical condition, being capable of understanding dietary recommendations, had enrolled in our hemodialysis program for over 2 months and signed the informed consent. On the other hand, exclusion criteria were not giving informed consent and a serum potassium level <5.5 nmol/l after two repetitive measurements at the beginning of the study.

In each phase, we analyzed sociodemographic data, related biochemical data, treatment adherence and compliance (Simplified Medication Adherence Questionnaire, SMAQ), gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale, GSRS), HD characteristics and usual medical treatment.

The following data were collected for all patients included in the study: main sociodemographic variables and variables associated with renal disease (sex, age, etiology of kidney failure, time on HD) at baseline; biochemical parameters related (serum levels of calcium [Ca], phosphorus [P], sodium [Na], magnesium [Mg], hemoglobin, platelet ate each phase and hemodialysis characteristics [KTV] according to 2nd-generation Daugirdas formula), dialysate calcium and potassium concentration, HD duration, dry weight and interdialytic weight gain at baseline as well as the end of the study.

Treatment adherence and compliance, and gastrointestinal symptoms were collected at each phase. Gastrointestinal symptomatology was measured through the Gastrointestinal Symptom Rating Scale (GSRS). It consists of 15 items grouped into five blocks according to the different symptoms (reflux, abdominal pain, diarrhea, indigestion and constipation), with a 7-point Likert-like scale where a rate of 1 and 5 represent the most positive and negative option respectively [19]. Finally, treatment adherence was measured through the Simplified Medication Adherence Questionnaire (SMAQ). This is a short and simple questionnaire comprised of six questions posed directly to the patient regarding medication-taking habits, which was originally used to validate adherence of patients to anti-retroviral treatments [20]. Any patient who responds to any of the items with a non-adherence answer was considered as non-compliant.

In reference to the standard medical treatment, data were collected on the type of phosphorus binders (calcium-based binders, non-calcium-based binders, binders with added magnesium and ferric chelators), traditional cardiovascular treatment (betablockers, Angiotensin Converting Enzyme Inhibitors [ACEI] or Angiotensin II Receptor Blockers [ARB]) as well as proton pump inhibitors and antacids.

Study Endpoints

The primary endpoint was to describe the prevalence, clinical characteristics and associated factors of chronic hyperkalemia in hemodialysis patients from the medical center. Secondary endpoints included the analysis of the control of serum potassium levels, treatment adherence, gastrointestinal symptomatology, safety profile and satisfaction with the different therapeutic options (dietetic measures, calcium polystyrene sulfonate resins and patiromer).

Statistical Analysis

Statistical analysis was carried out using SPSS version 24.0 (SPSS Inc., Chicago, IL, USA). Quantitative variables were expressed using the mean and standard deviation. The qualitative variables were expressed as a percentage. The comparison of quantitative data was carried out using the Wilcoxon test for non-parametric related variables, and the qualitative data was compared using the McNemar test; statistical significance for any comparison was set at a value of p<0.05.

Results

Patient Characteristics

Out of 65 identified patients, only 27 participants had a serum potassium level higher than 5.5mEq/l. A confirmatory analysis included 19 patients, with two and four of them either being excluded or discontinued the trial (three due to hospital admissions and one because of acute confusional syndrome), respectively. Therefore, a total of 13 patients, with a mean age of 63.8±14.1 years and 46.4±41.6 months in hemodialysis, took part in the study. Chronic tubulointerstitial nephritis was the most common cause of kidney failure (n=4, 30.8%), followed by nephroangiosclerosis, diabetic nephropathy and hepatorenal polycystic kidney disease (all n=2, 15.4%). Regarding comorbidities, all participants had arterial hypertension, with most of them having dyslipidemia (n=7, 53.8%), cardiopulmonary insufficiency (n=6, 46.2%) and/or smoking (n=6, 46.2%), respectively. Most of the participants underwent hemofiltration (n=11, 84.6%) and had an arteriovenous fistula (n=10, 76.9%; Table 1). At baseline, all the patients were treated with renin angiotensin aldosterone system inhibitors (RAASi) during the study (69.2% ACEI, 30.8% ARB) according to their clinical condition. No patient received mineralpcorticoids receptor antagonist and 22.5% received betablockers. In reference to the percentage and type of phosphorus binders, a 38.4%, 53.8%, 15.4% and 7.6% received calcium-based binders, non-calcium-based binders, binders with added magnesium and ferric chelators, respectively. A total of 69.2% received proton pump inhibitors and 15.4% antiacids. All the patients had 1.5 mEq/l potassium and 3.0 mmol/l calcium dialysate.