Potassium Binders Research Articles

Managing the Transition from Patient-Centered Care to Protocol.

Managing the Transition from Patient-Centered Care to Protocol David Slakter I learned that I would need a kidney transplant in the summer of 2015. This was not a complete surprise to me, as I had been subjected to a number of tests and invasive procedures to investigate nephritis since I was a child. I had heard similar stories of clinicians performing repeated tests on my father for similar reasons without any conclusions. Following my recommendation for transplant and consultation with genomics specialists, the cause of my kidney failure was determined to be Alport syndrome. What made Alport syndrome so difficult to diagnose in my case was that the associated mutation is a rare, autosomal-dominant one that has only recently been associated with the condition. After reviewing the data on survival rates for transitioning to dialysis versus a transplant, my family and I then considered the success rates for living versus cadaver donors, and the success rates at various transplant centers. The current data favor the long-term outcomes of transplant over dialysis and living over cadaver donors. Since we had decided to focus on searching for a live donor, my nephrologist recommended contacting Renewal, an organization that specializes in connecting those in need of a kidney transplant with live donors and providing support for donors to make the donation process less burdensome. On Renewal’s recommendation, my family and friends reached out across their social networks to search for potential donors. Many of those tested for compatibility were eliminated on basic matching criteria, others due to previously undiagnosed medical problems. Finally, the wife of a childhood friend came forward as an eligible donor and was also an incredibly close match on the antigens tested for kidney transplants. Having a living donor who was also a friend made the transplant experience somewhat less intimidating than it might have been. It meant the transformation of an existing relationship with someone already close to me, with fewer open questions about what may have motivated them to be so generous than if the donor had been someone I did not know. It also meant our families could be together in the waiting room, and that we shared in each other’s recoveries. Life post-transplant has been a significant improvement from what it was like immediately beforehand. Before my transplant, I regularly weighed food and consulted nutrition charts to gauge how much potassium I was consuming. To prevent too much potassium from building up in my bloodstream, I had to take sodium polystyrene [End Page 111] regularly. As one might guess from the name, it tastes much like burnt Styrofoam, and I could only ingest it with copious amounts of fruit-flavored syrup (strawberry covered up the awful flavor the best). There are other potassium binders on the market now, so fewer people with kidney failure will likely need to engage in such gustatory experimentation. I was also able to engage in more activities than what was possible even years before my transplant. I had long experienced difficulty with aerobic exercises, but assumed the reason was merely being out of shape. Though I have always walked regularly, even the one-mile walk from my office to my apartment had become a chore by the end. Within a few months after my transplant, I was riding a bicycle all over NYC, from Harlem to Brooklyn and back regularly, and hiking trails in nearby state parks. I began sessions with a personal trainer and attained a level of fitness I had not reached since I played soccer as a child. The transition from personalized care to one more driven by protocol has been a surprising and challenging aspect of the transplant process. While my previous experience with medical treatment has been individual meetings with physicians, my post-transplant care is managed by a team of nephrologists and other specialists in transplant care. My initial transplant nephrologist was automatically assigned to me. Because the standard of care for transplant patients is often driven by protocol, my assigned nephrologist recommended a biopsy on my transplanted kidney due to results in my recent lab tests. When pressed on the necessity of a biopsy in my case versus...

Comment on Montagnani et al. Optimization of RAASi Therapy with New Potassium Binders for Patients with Heart Failure and Hyperkalemia: Rapid Review and Meta-Analysis. J. Clin. Med. 2021, 10, 5483.

The recent rapid review and meta-analysis by Montagnani et al. [...].

Comparative efficacy of patiromer and sodium polystyrene sulfonate on potassium levels in chronic haemodialysis patients: a randomized crossover trial.

ABSTRACTBackgroundHyperkalaemia is frequent in haemodialysis (HD) patients and associated with increased cardiovascular mortality. Despite routine clinical use, evidence regarding the efficacy of potassium (K+) binders in HD is scant. We wished to compare the efficacy of patiromer (PAT) and sodium polystyrene sulfonate (SPS) on K+ levels in this setting.MethodsWe screened patients in three HD centres with pre-HD K+ value between 5.0 and 6.4 mmol/L, after an initial 2-week washout period for those previously on K+ binders. We included patients in an unblinded two-arm crossover trial comparing SPS 15 g before each meal on non-dialysis days with PAT 16.8 g once daily on non-dialysis days with randomized attribution order and a 2-week intermediate washout period. The primary outcome was the mean weekly K+ value.ResultsWe included 51 patients and analysed 48 with mean age of 66.4 ± 19.4 years, 72.9% men and 43.4% diabetics. Mean weekly K+ values were 5.00 ± 0.54 mmol/L, 4.55 ± 0.75 mmol/L and 5.17 ± 0.64 mmol/L under PAT (P = .003), SPS (P < .001) and washout, respectively. In direct comparison, K+ values and prevalence of hyperkalaemia were lower under SPS as compared with PAT (P < .001). While the incidence of gastrointestinal side effects was similar between treatments, SPS showed lower subjective tolerability score (6.0 ± 2.4 and 6.9 ± 1.9) and compliance (10.8 ± 20.4% and 2.4 ± 7.3% missed doses) as compared with PAT (P < .001 for both).ConclusionBoth PAT and SPS are effective in decreasing K+ levels in chronic HD patients. However, at the tested doses, SPS was significantly more effective in doing so as compared with PAT, despite lower tolerability and compliance. Larger randomized controlled trials should be conducted in order to confirm our findings and determine whether they would impact clinical outcomes.

MO904: Potassium Intake Does Not Predict High Serum Potassium Levels in Haemodialysis Dash Diet Consumers

Abstract BACKGROUND AND AIMS As high serum potassium levels can lead to adverse outcomes in haemodialysis (HD) patients, dietary potassium is frequently restricted in these patients. However, recent studies have questioned whether dietary potassium really affects serum potassium levels. Dietary approaches to stop hypertension (DASH) emphasizes the consumption of potassium rich foods, specially from plant sources, such as: fruits, vegetables, whole grains, nuts and seeds. The aim of this study was to analyze the association between the DASH dietary pattern and serum potassium levels. METHOD This was an observational cross-sectional multicentre study with 582 HD patients from 37 dialysis centers. Clinical and biochemical data were registered. Dietary intake was obtained using the Food Frequency Questionnaire. Adherence to DASH dietary pattern was obtained from Fung´s DASH index (8–40 points). For the statistical analysis, Fung´s DASH index was categorized into terciles and mean differences were analyzed with one-way ANOVA. Linear regression was used to analyze the relationship between serum potassium and adherence to the Dash dietary pattern. The multivariate model was adjusted to age, gender, presence of diabetes mellitus, energy intake, dietary potassium intake, residual diuresis, dialysis adequacy (Kt/V), dialysis vintage and intake of potassium binders. All statistical tests were performed using SPSS 26.0 software. A P-value lower than 0.05, was considered statistically significant. RESULTS Patients’ mean age was 67.8 ± 17.7 years and median HD vintage was 65 (43–104) months. Mean serum potassium was 5.3 ± 0.67 mEq/L, dietary potassium intake was 2465 ± 1005 mg/day and mean Fung´s Dash Index was 23.9 ± 3.9. Of the whole sample, 36.4% of the patients presented low adherence to the DASH dietary pattern (0–22 points), 39.0% presented a moderate adherence (23–26 points) whereas 24.6% a high adherence (≥27 points). Comparing to the lower adherence, patients with a higher adherence to the DASH dietary pattern were older (P &amp;lt; 0.005), presented lower serum potassium (P = 0.021), serum sodium (P = 0.028), albumin (P = 0.030), creatinine (P &amp;lt; 0.005), energy intake (P = 0.006), protein intake (P = 0.010), total fat intake (P = 0.001), sodium intake (P &amp;lt; 0.005), lean tissue index (P = 0.006) and higher carbohydrates intake (P = 0.007), fiber intake (P &amp;lt; 0.005), potassium intake (P &amp;lt; 0.005), body mass index (P = 0.002) and fat tissue index (P &amp;lt; 0.005). No differences were observed in potassium binders, Kt/V, C-reactive protein nor haemoglobin. A higher adherence to this dietary pattern was a predictor of lower serum potassium levels (P = 0.004), even in the adjusted model (P = 0.016). CONCLUSION Most of the patients presented a moderate adherence to the DASH dietary pattern. Following this dietary pattern, which is rich in potassium, is not associated with increased serum potassium levels in HD patients. What is more, a higher adherence to the DASH dietary pattern predicts lower serum potassium levels. Therefore, tight dietary potassium restrictions may not be adequate, at least for those with a DASH diet plan as a more flexible diet, especially regarding plant-based foods rich in potassium, may promote other health benefits and reduce patient´s dietary plan limitations.

MO487: Rates of Hyperkal a EMIA and Management Patterns in a Tertiary Outpatient Renal Clinic

Abstract BACKGROUND AND AIMS The optimal ambulatory management of hyperkalaemia (HK) in patients with chronic kidney disease (CKD) is still an important unmet challenge. Common strategies include dose reduction or discontinuation of nephroprotective medications (e.g. renin-angiotensin-aldosterone system inhibitors [RAASi]), dietary restriction of potassium (K), loop diuretics, bicarbonate and sodium polystyrene sulfonate; all the above interventions are characterized by specific pitfalls and limitations. However, new potassium binders are available that might improve the management of chronic hyperkalaemia. In the light of their widespread use, it will be important to increase our knowledge of the incidence, characteristics and current real-life management patterns of hyperkalaemia in CKD patients. METHOD We performed a retrospective analysis of patients followed at our tertiary outpatient renal clinic from 1 April 2016 to 31 December 2021. HK was defined as serum K &amp;gt; 5.0 mmol/L and stratified according to severity. eGFR was estimated with the CKD-EPI equation and stratified according to the KDIGO criteria. The time span between each episode of HK was assessed with Poisson regression models. A sample of 100 HK events was selected at random for manual chart review of the management strategies performed: Information was abstracted using a standardized form. RESULTS The final analysis included 1844 patients, contributing 4480 occasions. Baseline characteristics by hyperkalaemia status are reported in Table 1. Patients with HK were older, with lower eGFR and a higher prevalence of diabetes. At least one episode of HK was documented in 525 patients (28.5%) and among them, 166 patients (31.6%) had at least two HK episodes (on average, 1.55 episodes/patient). HK events were more frequent among patients with more advanced stages of CKD. The time span between episodes decreased significantly (Fig. 1): on average, each episode was 17% [95% confidence interval (95% CI), 3%–29%) closer to the subsequent (P = .016). Of the 100 HK episodes randomly reviewed, 79% received no intervention, whereas 21% triggered at least one intervention. The probability of intervention increased with increasing severity of HK: 8.6%, 35.9%, 50.0% and 100% for K-values 5.0–5.4, 5.5–5.9, 6.0–6.4 and ≥6.5 mmol/L, respectively. Most interventions included dose reduction or discontinuation of RAASi. One patient was sent to the emergency department for urgent examination and treatment (K 7.0 mmol/L). CONCLUSION Hyperkalaemia is a common and recurring problem for patients with renal impairment: It occurs in almost one-third of the overall population of this study, and many hyperkalaemic patients experience recurring events. As expected, the prevalence rates of hyperkalaemia increase with worsening CKD severity. Furthermore, the decreased time span between consecutive episodes highlights an accelerated recurrence pattern of hyperkalaemia despite interventions.

MO199: A Phase 1, Open-Label, Crossover Study Evaluating The Effect of a Single Dose of Sodium Zirconium Cyclosilicate on the Pharmacokinetics of Tacrolimus and Cyclosporin

Abstract BACKGROUND AND AIMS Sodium zirconium cyclosilicate (SZC) is a novel, oral, highly selective potassium binder approved for the treatment of hyperkalaemia (HK) in adults. As well as binding potassium, SZC binds hydrogen ions in the acidic environment of the stomach, causing a transient increase in gastric pH which may alter absorption of oral drugs with gastric pH-dependent bioavailability. HK is a recognized issue for renal transplant patients. Tacrolimus and cyclosporin are important drugs in transplant patients, but it is unknown if co-administration of SZC affects their pharmacokinetic (PK) profiles. The aim of this study was to evaluate if the PK profiles of tacrolimus and cyclosporin are altered by SZC co-administration in healthy subjects. METHOD This was an open-label, randomized-sequence, 2-cohort crossover study conducted at a site in Germany (NCT04788641). Healthy adults aged 18–50 years were assigned to either cohort 1 (tacrolimus) or cohort 2 (cyclosporin). Subjects in cohort 1 (tacrolimus) received a single dose of tacrolimus 5 mg and tacrolimus 5 mg + SZC 15 g in a random order. Subjects in cohort 2 (cyclosporin) received a single dose of cyclosporin 100 mg and cyclosporin 100 mg + SZC 15 g in a random order. Drug administrations were planned to occur after a 12-h overnight fast and a ≥14-day washout period between treatment periods. Blood samples were collected pre-dose and post-dose up to 72 h. The primary PK endpoints for tacrolimus and cyclosporin were maximum observed blood concentration (Cmax) and area under the concentration-time curve (AUC) from time zero to infinity (AUCinf). Secondary endpoints for tacrolimus and cyclosporin were AUC from time zero to the time of the last quantifiable concentration (AUClast), half-life associated with terminal λz of a semi-logarithmic concentration-time curve (t½λz), and time to reach maximum observed concentration (tmax). The difference in mean PK parameters was analysed using a mixed effects model following a natural logarithmic transformation, with period, treatment and sequence as fixed effects, and subject nested within sequence as random effects. Safety and tolerability evaluation included assessment of adverse events (AEs). RESULTS Overall, 31 subjects were enrolled in each cohort; 30 subjects in cohort 1 (tacrolimus) and 29 in cohort 2 (cyclosporin) completed the study. Tacrolimus exposure was lower with tacrolimus + SZC compared with tacrolimus alone (Figure 1); Cmax geometric mean ratio (GMR): 71.1% (90% confidence interval [CI] 65.4–77.2), AUCinf: 62.9% (55.6–71.1), AUClast: 65.6% (58.7–73.2). t½λz of tacrolimus was similar between tacrolimus + SZC and tacrolimus alone (GMR: 98.4%; 90% CI 94.6–102.4). Median tmax of tacrolimus was earlier with tacrolimus + SZC (1.50 h) compared with tacrolimus alone (1.75 h; GMR: 83.9%; 90% CI 73.4–95.8). Cyclosporin exposure was similar with cyclosporin + SZC compared with cyclosporin alone (Figure 2); Cmax GMR: 102.9% (90% CI 96.1–110.1), AUCinf: 97.2% (92.9–101.7), AUClast: 97.0% (92.7–101.6). t½λz of cyclosporin was comparable with cyclosporin + SZC and cyclosporin alone (GMR: 94.1%; 90% CI 85.7–103.3). Median tmax of cyclosporin was 1.25 h with cyclosporin + SZC and 1.50 h with cyclosporin alone (GMR: 97.6; 90% CI 87.2–109.2). A total of 15 AEs were reported in 13 subjects with tacrolimus + SZC, 12 AEs in 7 subjects with tacrolimus, 9 AEs in 7 subjects with cyclosporin + SZC and 8 AEs in 8 subjects with cyclosporin. AEs were generally mild in intensity in all groups. There were no serious AEs and no systematic pattern in preferred terms. CONCLUSION Tacrolimus exposure was lower when co-administered with SZC 15 g, which has the potential to reduce its immunosuppressive efficacy. As for other oral drugs with drug–drug interactions with SZC, tacrolimus should be administered ≥ 2 h before or after SZC. The PK profile of cyclosporin was not affected by SZC co-administration.

Current Management and Treatment for Patients with Chronic Kidney Disease

The incidence of chronic kidney disease (CKD) is rising in many parts of the world and primary care providers are poised to be the first point of contact for these patients. The optimal management of patients with CKD include early detection, cause identification, CKD progression retardation (including dietary support, blood pressure control, drug therapeutics), management of comorbid conditions, acute kidney injury prevention, and knowing when to refer for specialist care. In general, the concept of CKD progression retardation involves patient education on topics such as lifestyle modification measures, e.g., diet, to reduce burden on the kidneys and use of medications that can confer renoprotection while causing little if any side effects. The advent of SGLT2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, and new potassium binders provides our patients with new hope to further lengthen the time to end-stage kidney failure. It is therefore necessary that stakeholders involved in the care of patients with CKD understand the latest evidence to optimise care and patient wellbeing.

The effect of sodium zirconium cyclosilicate on acid-base balance inchronic kidney disease.

Hyperkalemia is a common electrolyte abnormality in chronic kidney disease (CKD). Sodium zirconium cyclosilicate (SZC) is a novel selective cation exchanger that is used to treat hyperkalemia and may also capture ammonium, which is of a similar size to potassium. We investigated the effect of SZC on acid-base balance in CKD patients. This retrospective study surveyed 20 patients with CKD whose serum potassium levels were maintained within the normal range by treatment with polysulfonate resin, which was replaced with SZC during the clinical course. We compared clinical parameters before and after changing medications. Changing the potassium binder from polysulfonate resin to SZC increased serum bicarbonate (p=0.016) and decreased blood urea nitrogen (p=0.017). Serum potassium levels were maintained within the normal range. Urine pH, anion gap, and osmolality gap were unchanged during treatment. No gastrointestinal symptoms were noted during the observation period. Our data suggest that SZC may improve not only hyperkalemia but also metabolic acidosis by increasing the excretion of ammonium from the intestinal tract in patients with CKD. SZC could be a more suitable medication for CKD patients with hyperkalemia and metabolic acidosis.

In-hospital mortality, length of stay, and hospitalization cost of COVID-19 patients with and without hyperkalemia

BackgroundHyperkalemia (HK) may be associated with poor clinical outcomes among COVID-19 patients. This study aimed to describe the prevalence of HK and evaluate the associations between HK and in-hospital mortality, intensive care unit (ICU) admission, length of hospital stay (LOS), and hospitalization cost among COVID-19 inpatients. MethodsA retrospective cohort study was conducted using a large hospital discharge database (PINC AI Healthcare Database) for COVID-19 inpatients discharged between April 1 and August 31, 2020. HK was defined with discharge diagnosis and potassium binder use. ResultsOf 192,182 COVID-19 inpatients, 12% (n = 22,702) had HK. HK patients were more likely to be older (median age 67 vs 63 years), male (63% vs 50%), black (30% vs 22%), and have a history of chronic kidney disease (45% vs 16%) or diabetes mellitus (55% vs 35%) than non-HK patients (all p<.001). A significantly higher proportion of patients with HK had in-hospital mortality (42% vs 11%, p<.001) than those without HK; this was persistent after adjusting for confounders (adjusted odds ratio [aOR] 1.69, 95% confidence interval [CI]1.62-1.77). Patients with HK were also more likely to be admitted to ICU (aOR 1.05, 95% CI 1.01-1.09), incur higher cost of care (adjusted mean difference $5,389) and have longer LOS (adjusted mean difference 1.3 days) than non-HK patients. ConclusionsPresence of HK was independently associated with higher in-hospital mortality, LOS, and cost of care among COVID-19 inpatients. Detecting and closely monitoring HK are recommended to improve clinical outcomes and reduce LOS and healthcare cost among COVID-19 patients.

Effect of Sodium Zirconium Cyclosilicate on Serum Potassium and Bicarbonate in Patients with Hyperkalemia and Metabolic Acidosis Associated with Chronic Kidney Disease: Rationale and Design of the NEUTRALIZE Study

Introduction: Sodium zirconium cyclosilicate (SZC) is a selective potassium (K⁺) binder for hyperkalemia management that provides rapid and sustained correction of hyperkalemia. The NEUTRALIZE study is investigating whether SZC, in addition to correcting hyperkalemia and maintaining normal serum K⁺, can provide sustained increases in serum bicarbonate (HCO₃⁻) in patients with hyperkalemia and metabolic acidosis associated with chronic kidney disease (CKD). Methods: This is a prospective, randomized, double-blind, placebo-controlled phase 3b study of US adults with stage 3–5 CKD not on dialysis with hyperkalemia (K⁺ >5.0–≤5.9 mmol/L) and low-serum HCO₃⁻ (16–20 mmol/L). In the open-label correction phase, all eligible patients receive SZC 10 g three times daily for up to 48 h. Patients who achieve normokalemia (K⁺ ≥3.5–≤5.0 mmol/L) are then randomized 1:1 to once-daily SZC 10 g or placebo for a 4-week, double-blind, placebo-controlled maintenance phase. The primary endpoint is the proportion of patients with normokalemia at the end of treatment (EOT) without rescue therapy for hyperkalemia. Key secondary endpoints include mean change in serum HCO₃⁻, the proportion of patients with an increase in serum HCO₃⁻ of ≥2 or ≥3 mmol/L without rescue therapy for metabolic acidosis, and the proportion of patients with serum HCO₃⁻ ≥22 mmol/L at EOT. Conclusions: NEUTRALIZE will establish whether SZC can provide sustained increases in serum HCO₃⁻ while lowering serum K⁺ in patients with hyperkalemia and CKD-associated metabolic acidosis and may provide insights on the mechanism(s) underlying the increased serum HCO₃⁻ with SZC treatment.

Cost-Effectiveness of Treating Patients with Chronic Kidney Disease and Prior Hyperkalemia with Renin-Angiotensin-Aldosterone System Inhibitor and Patiromer: A Swiss Public Healthcare Perspective.

IntroductionHyperkalemia is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD). Patiromer (Veltassa®) is an oral potassium binder indicated for the treatment of hyperkalemia in adults. We evaluated the impact of patiromer on the Swiss healthcare resources when used in patients with CKD and hyperkalemia who were on renin–angiotensin–aldosterone system inhibitor (RAASi) treatment.MethodsWe built a decision tree and calculated the number needed to treat (NNT) to prevent hyperkalemia, hospitalization, and death based on published aggregated data. The decision tree was populated with available data from relevant patiromer clinical trials and data were applied to create a simple model showing the expected effectiveness of adding patiromer to the treatment of patients with medium-to-severe stage CKD on RAASi compared to RAASi only. Adapting the model to the Swiss healthcare system allowed us to estimate the impact of the new treatment on healthcare expenditures from a payer as well as a Swiss public healthcare perspective.ResultsPatiromer reduced the absolute risk for recurrent hyperkalemia by 48% within 8 weeks, resulting in an NNT of 2.1 [95% CI 1.4, 3.7]. If one assumes that 90%, 50%, or 10% of all moderate-to-severe hyperkalemic events lead to hospitalization, the NNT to prevent one hospitalization would be 2.5, 4.4, and 22.2, respectively. On the basis of the death rate of patients with mild or moderate-to-severe hyperkalemia, and the prevalence of mild or moderate-to-severe hyperkalemia in the treatment and control groups, the NNT was 78.7 [95% CI 64.0, 99.3] to prevent one death. Patiromer resulted in expected cost offsets of CHF 303 (1 CHF = 0.95 EUR as of 2022) per patient over 8 weeks in Switzerland.ConclusionPatiromer used for the treatment of CKD reduces hyperkalemia recurrence leading to improved patient care. This results in substantial offset costs for the Swiss healthcare system.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02123-3.

Effects of renin-angiotensin system inhibitors on the incidence of unplanned dialysis.

Unplanned dialysis initiation is associated with poor outcomes. It is controversial whether patients with advanced chronic kidney disease (CKD) should receive renin-angiotensin system (RAS) inhibitor therapy. The aim of this study was to evaluate the effect of RAS inhibitor therapy in patients with advanced CKD on the incidence of unplanned dialysis initiation. This single-center, retrospective study included patients who started maintenance dialysis at our hospital between April 2014 and March 2021. Patients who initiated dialysis within 6 months of nephrology referral or after kidney transplant were excluded. Among 334 patients (aged 70.0 [59.0-79.0] years; 28.4% women), 186 (55.7%) and 148 (44.3%) had planned and unplanned dialysis initiation, respectively. Multivariate logistic regression analysis revealed that the use of RAS inhibitors was significantly associated with a lower incidence of unplanned dialysis initiation (odds ratio [OR], 0.36; P < 0.01). Female sex (OR, 0.41; P < 0.05), use of potassium binders (OR, 0.28; P < 0.001), earlier referral to nephrology (OR, 0.39; P < 0.01), and earlier discussion of renal replacement therapy (OR, 0.33; P < 0.001) were also significantly associated with a lower incidence, whereas older age (OR, 1.28; P < 0.05), higher Charlson Comorbidity Index (OR, 1.24; P < 0.05), and faster decline in kidney function (OR, 1.29; P < 0.01) were associated with a higher risk of unplanned dialysis initiation. RAS inhibitor therapy in patients with advanced CKD is associated with a lower risk of unplanned dialysis initiation.

Can Novel Potassium Binders Liberate People with Chronic Kidney Disease from the Low-Potassium Diet? A Cautionary Tale.

The advent of new potassium binders provides an important breakthrough in the chronic management of hyperkalemia for people with CKD. In addition to the direct benefits of managing hyperkalemia, many researchers and clinicians view these new medications as a possible means to safely transition patients away from the low-potassium diet to a more healthful eating pattern. In this review, we examine the mechanisms of potassium binders in the context of hyperkalemia risk related to dietary potassium intake in people with CKD. We note that whereas these medications target hyperkalemia caused by potassium bioaccumulation, the primary evidence for restricting dietary potassium is risk of postprandial hyperkalemia. The majority of ingested potassium is absorbed alongside endogenously secreted potassium in the small intestines, but the action of these novel medications is predominantly constrained to the large intestine. As a result and despite their effectiveness in lowering basal potassium levels, it remains unclear whether potassium binders would provide protection against hyperkalemia caused by excessive dietary potassium intake in people with CKD. Until this knowledge gap is bridged, clinicians should consider postprandial hyperkalemia risk when removing restrictions on dietary potassium intake in people with CKD on potassium binders.

The Enabling Potential of Device Therapy for Heart Failure

Patients with heart failure (HF) have poor prognoses despite substantial advances in therapeutic development. Comprehensive guideline-directed medical therapy (GDMT) is infrequently achieved in practice, especially at target doses. 1 Greene SJ Fonarow GC DeVore AD Sharma PP Vaduganathan M Albert NM et al. Titration of medical therapy for heart failure with reduced ejection fraction. J Am Coll Cardiol. 2019; (21): 2365-2383 Google Scholar The effects of GDMT on hemodynamic, electrolyte and renal parameters limit clinicians’ eagerness to initiate and titrate these drugs. Indeed, the most common reason for the inability to achieve target GDMT is that a patient is on “maximally tolerated” therapy. 2 Fiuzat M Ezekowitz J Alemayehu W Westerhout CM Sbolli M Cani D et al. Assessment of limitations to optimization of guideline-directed medical therapy in heart failure from the GUIDE-IT Trial: a secondary analysis of a randomized clinical trial. JAMA Cardiol. 2020; 5: 757-764 Google Scholar GDMT intolerance is associated with particularly unfavorable outcomes. 3 Morris AA Khazanie P Drazner MH Albert NM Breathett K Cooper LB et al. Guidance for timely and appropriate referral of patients with advanced heart failure: a scientific statement from the American Heart Association. Circulation. 2021; 144: e238-e250 Google Scholar Whether this is related to fragile hemodynamic status, lack of exposure to beneficial therapies, or some combination of the 2 has not been fully elucidated. Some patients who have this clinical profile are eligible for advanced therapies, but the vast majority will not undergo cardiac replacement. 4 Truby LK Rogers JG. Advanced heart failure: epidemiology, diagnosis, and therapeutic approaches. JACC Heart Fail. 2020; 8: 523-536 Google Scholar ,5 Birks EJ Drakos SG Patel SR Lowes BD Selzman CH Starling RC et al. Prospective multicenter study of myocardial recovery using left ventricular assist devices (RESTAGE-HF [Remission from Stage D Heart Failure]): medium-term and primary end point results. Circulation. 2020; 142: 2016-2028 Google Scholar Thus, there is an ongoing need for strategies that can facilitate GDMT tolerance. Drug therapies have long been used to facilitate tolerance of beneficial devices (eg, dual antiplatelet therapy after percutaneous coronary intervention) and other drugs (eg, potassium binders to facilitate renin-angiotensin-aldosterone system inhibitor use), but most cardiac devices have not been intentionally applied to facilitate tolerance of beneficial drugs (Fig. 1), some notable exceptions being myocardial recovery in patients with durable mechanical circulatory support (MCS)5 and pacemaker implantation to facilitate beta-blocker tolerance for arrhythmia management.

POS-306 OUTPATIENT TREATMENT PATTERNS IN HYPERKALEMIA: AN OBSERVATIONAL STUDY IN THE US

Hyperkalemia (HK), a serum potassium concentration above 5.0 mEq/L, is a potentially severe condition that may result in arrhythmias and sudden death. Renin-angiotensin-aldosterone system inhibitor (RAASi) treatment is a cornerstone in the management of chronic kidney disease (CKD) and heart failure (HF), but can also induce HK. Potassium binders are a key pillar in the treatment of HK, but routine use of conventional binders such as sodium polystyrene sulfonate (SPS) is hampered by questionable effectiveness and safety concerns.

Can patiromer allow for intensified renin–angiotensin–aldosterone system blockade with losartan and spironolactone leading to decreased albuminuria in patients with chronic kidney disease, albuminuria and hyperkalaemia? An open-label randomised controlled trial: MorphCKD

IntroductionChronic kidney disease (CKD) is associated with significantly increased morbidity and mortality. No specific treatment of the underlying condition is available for the majority of patients, but ACE-inhibitors (ACE-I) and...

POS-094 PSEUDOHYPERKALEMIA AND THE NEWLY INTRODUCED POTENT POTASSIUM BINDERS: A CALL FOR IMPERATIVE CAUTION – TWO CASE SERIES

Pseudohyperkalemia, first described in 1955 by Hartmann and Mellinkoff, is the presence of a marked elevation of serum potassium in the absence of clinical evidence of electrolyte imbalance. In pseudohyperkalemia, simultaneously measured serum potassium exceeds plasma potassium by >0.4 mmol/L. Two patients with pseudohyperkalemia were inadvertently administered inappropriate potassium binder therapy for weeks to months before the diagnosis of pseudohyperkalemia was entertained and confirmed. Potassium binders were promptly discontinued immediately after the diagnosis of pseudohyperkalemia was established.

Cost Consequence Analysis of the Management of Hyperkalemia by Patiromer and Optimization of Renin-Angiotensin-Aldosterone System Inhibitors Therapy in Chronic Kidney Disease Patients in Saudi Arabia

Renin-angiotensin-aldosterone system inhibitors (RAASi) have been shown to improve outcomes in chronic kidney disease (CKD) patients but are associated with an increased risk of hyperkalemia in this vulnerable population. Hyperkalemia often leads to patients' downtitrating or discontinuing RAASi which can result in sub-optimal health outcomes. The objective is to evaluate the cost and health benefits of maintaining normokalemia using patiromer, an oral potassium binder while optimizing RAASi therapy in CKD patients in the Kingdom of Saudi Arabia. The medium-to long-term costs and health outcomes of patients with CKD stage 3-4 and raised serum potassium levels (≥5.5 mmol/L) at baseline were estimated, from a Saudi Arabia payer perspective, using a Markov state-transition model simulating the natural progression of CKD depending on patients' serum potassium level and usage of RAASi at different dosages. The analysis demonstrated that appropriate management of hyperkalemia, enabling optimization of RAASi, leads to cost and health benefits. The cost of patiromer is offset by 68% due to a reduction in management costs associated with CKD progression, hyperkalemia-related hospitalization, and cardiovascular (CV) events. Over a 10-year time horizon, a pool of 300 patients treated with patiromer experience increased life-expectancy [+3.78 life-years (LYs)] and slower disease progression, with decreased time spent in end-stage renal disease (-9.59 LYs). Patiromer may deliver value to both CKD patients and payers in Saudi Arabia, leading to better health outcomes for the former and reduced cost of management of CKD progression and CV events at low additional costs for the latter.

Assessment of Patiromer Monotherapy for Hyperkalemia in an Acute Care Setting

Hyperkalemia is a common electrolyte disorder in hospitalized patients; however, the clinical usefulness of administering patiromer for reduction of serum potassium levels in this setting is unknown. To evaluate the outcomes associated with patiromer as monotherapy in patients with acute hyperkalemia in an acute care setting. This cohort study used electronic health record data from adult patients treated with patiromer for acute hyperkalemia in emergency departments, inpatient units, and intensive care units at an urban, academic medical center in the Bronx, New York, between January 30, 2018, and December 30, 2019. Data analysis was conducted between June 2020 and February 2021. A single dose of oral patiromer (8.4 g, 16.8 g, or 25.2 g). The primary outcome was the mean absolute reduction in serum potassium level from baseline at 3 distinct time intervals after patiromer administration: 0 to 6 hours, greater than 6 to 12 hours, and greater than 12 to 24 hours. Key secondary outcomes were the incidence of hypokalemia and potassium reduction stratified by baseline potassium level and care setting. Among 881 encounters of patiromer treatment, the mean (SD) age of patients was 67.4 (14.4) years; 463 encounters (52.6%) were for male patients, and most (338 [38.4%]) were for patients who identified as non-Hispanic Black. The mean (SD) baseline serum potassium level was 5.60 (0.35) mEq/L (to convert to mmol/L, multiply by 1.0), and within the first 6 hours after patiromer administration, the mean (SD) potassium reduction was 0.50 (0.56) mEq/L (P < .001). Both absolute and relative potassium reduction from baseline varied across baseline hyperkalemia severity but not by care setting. The lowest dose of patiromer (8.4 g) was used in 721 encounters (81.8%), and in 725 encounters (82.3%), no further doses of a potassium binder were required. Hypokalemia was noted in 2 encounters (0.2%) at 24 hours after patiromer administration. In this cohort study of patients with acute, non-life-threatening hyperkalemia, a single dose of patiromer was associated with a significant decrease in serum potassium levels and a low incidence of hypokalemia. These findings suggest that patiromer monotherapy may be useful in an institutional setting for managing elevated potassium levels and minimizing the risk of hypokalemia associated with other potassium control measures.

Experience of a Bespoke Hyperkalaemia Clinic to Facilitate Prescribing of Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Heart Failure with Reduced Ejection Fraction

Background: Renin-angiotensin-aldosterone system inhibitors (RAASi) improve prognosis in patients with heart failure with reduced ejection fraction (HFrEF), but suboptimal dosing or discontinuation of these medications often occurs due to RAASi-associated hyperkalaemia. We established a nephrology-led hyperkalaemia clinic to oversee prescribing of patiromer, an oral potassium binder, to facilitate RAASi optimization. Methods: The clinic was established in July 2019 at a nephrology tertiary centre in the UK. Patients with HFrEF who were unable to increase RAASi dosage due to hyperkalaemia were referred to the clinic, where all patients commenced patiromer 8.4 g daily. RAASi adjustments were deferred to the referring teams. Study outcomes included the percentage of patients who achieved a RAASi dose increase and the proportion of patients with normokalaemia at follow-up. Outcomes were evaluated until 1 May 2021. Results: A total of 34 patients were reviewed in the clinic between July 2019 and December 2020. Mean age was 71.6 years (±10.6 years), 56% had diabetes, and 71% had chronic kidney disease stages 3a-5; mean estimated glomerular filtration rate was 56 mL/min/1.73 m² (±21 mL/min/1.73 m²). During follow-up, 13 patients discontinued patiromer (6 of whom did so due to gastrointestinal side effects) and were discharged; 2 patients died from non-hyperkalaemia-related illness; one switched to an alternative potassium binder. Over a mean follow-up of 13.4 months (±5.8 months), 17 of the 20 patients (85%) who continued with a potassium binder achieved a RAASi dose increase, with 4 patients (20%) receiving maximal dosages. This was attained by achieving normokalaemia during follow-up. No patients required magnesium supplementation. Of the 19 patients on patiromer, 12 continued this therapy for more than 12 months and 4 received it safely for 20 months. Discussion/Conclusion: Patiromer prescribing in a nephrology-led hyperkalaemia clinic facilitated RAASi up-titration in patients with HFrEF by controlling potassium levels.