Zirconium Cyclosilicate Research Articles

Abstract 4117180: Hyperkalemia-Related Hospitalization Associated with Short-Term vs. Long-Term Outpatient SZC Therapy Among RAASi Users: The GALVANIZE Outcome study

Introduction: Patients receiving renin-angiotensin-aldosterone system inhibitors (RAASi) are at increased risk of developing hyperkalemia (HK). Sodium zirconium cyclosilicate (SZC) is used to treat HK, but the impact of duration of SZC on healthcare resource utilization (HRU) in RAASi users is unknown. The GALVANIZE Outcome study compared HK-related HRU among RAASi users between long-term and short-term SZC users. Methods: Adults with ≥1 outpatient prescription for SZC (index date) and ≥1 RAASi prescription spanning the index date were identified from a large US insurance claims database (7/2018-12/2022) and were stratified based on duration of SZC use. Long-term SZC users (>90 days) and short-term SZC users (≤30 days) were exactly and propensity score matched on key baseline characteristics. Rates of HK-related hospitalizations or emergency department (ED) visits, HK-related ED visits, and HK-related hospitalizations were compared during follow-up from index to the earliest of 6 months post-index, end of data availability, other potassium binder use, or re-initiation of SZC post-discontinuation. Results: Among 1,586 matched pairs, the mean age was 65.5 years, 41.0% of patients were female, and most patients had any stage chronic kidney disease (91.9%), hypertension (90.8%), and diabetes (73.4%). Also, 30.0% of patients had heart failure. The most used RAASi therapies at index were angiotensin-converting enzyme inhibitors (57.3%) and angiotensin-receptor blockers (56.3%). Patients with long-term SZC use had a 44% lower rate of HK-related hospitalizations or ED visits, a 41% lower rate of HK-related hospitalizations and a 52% lower rate of HK-related ED visits than patients with short-term SZC use during follow-up (all p<0.01; Figure 1). Conclusions: Among patients with RAASi and SZC therapy use, long-term SZC use was associated with significantly lower rates of HK-related HRU compared to matched patients with short-term SZC use. Funding: AstraZeneca

Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients with Heart Failure

Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients with Heart Failure

Sodium Zirconium Cyclosilicate for Renin-Angiotensin-Aldosterone System Inhibitor Optimization in Patients with Heart Failure with Reduced Ejection Fraction: A Retrospective Analysis.

In this retrospective analysis, we evaluate the effectiveness of the potassium (K+) binder sodium zirconium cyclosilicate (SZC) in maintaining normokalemia and facilitating the initiation, optimization, and maintenance of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with heart failure (HF) with reduced ejection fraction (HFrEF). A total of 44 patients with HFrEF and a history of hyperkalemia who were receiving SZC to enable the prescription of RAASi were identified from two district general hospital sites. Retrospective analysis was performed to determine biochemical response, alterations in pharmacotherapy, and subsequent HF outcomes following initiation of SZC. Mean K+ was reduced by 0.9mmol/L within 1month of initiation of SZC; mean K+ after 12months of treatment was 4.8mmol/L with a median (interquartile range) duration of treatment of 13 (8.4-15.1) months. Following SZC treatment, 100% of patients received an angiotensin receptor-neprilysin inhibitor (18% increase) and 93% received a mineralocorticoid receptor antagonist (41% increase), with 59% and 37% achieving guideline-recommended dosing, respectively. Ninety-one percent of patients were able to receive triple or quadruple therapy with the addition of a beta-blocker and a sodium glucose co-transporter2 inhibitor. Reduced rates of hospitalization for HF (HHF) were observed with 12 episodes per 100 patient-years recorded (reduced from 21) in addition to improvements in mean left ventricular ejection fraction (29-36%) and median N-terminal pro-B-type natriuretic peptide (3458-2055ng/L, 45% median reduction). Renal function (creatinine clearance increased from 48.4 to 49.3ml/min) and systolic blood pressure (decreased from 124 to 122mmHg) were similar following optimization, and no tolerability issues were identified. Extended real-world treatment with the K+ binder SZC was effective at maintaining normokalemia, and was associated with a greater uptake of RAASi, a reduced rate of HHF, and improvements in cardiac biomarkers in patients with HFrEF.

Cardiovascular mortality with oral potassium-binders in patients with CKD and heart failure

Abstract Introduction Hyperkalemia is an inherent consequence of advancing chronic kidney disease (CKD) as a result of the kidney’s decreased ability to excrete potassium. Heart failure patients with concomitant CKD may not tolerate maximum doses of guideline-directed medical therapies (GDMT) like ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), angiotensin receptor/neprilysin inhibitors (ARNI) and mineralocorticoid receptor antagonists (MRA) due to dose-limiting hyperkalemia. Many randomized controlled trials in heart failure exclude patients with advanced CKD. Two oral therapies exist to manage hyperkalemia - patiromer sorbitex calcium and sodium zirconium cyclosilicate. This study aims to identify the potassium-binder with better outcomes as defined by less readmissions, hyperkalemia episodes, and death. Purpose This project was undertaken to better understand the impact of using potassium-binders in CKD patients with heart failure. Improved management of hyperkalemia will be an avenue for optimization of GDMT in this population. Methods and materials The TriNetX research network was used for this study. Two cohorts of patients were created by using International Classification of Disease 10 (ICD-10) codes and CPT codes. Both cohorts consisted of patients with no prior history of hyperkalemia within 30 days of hospital discharge at which time one cohort was prescribed patiromer and the other received sodium zirconium cyclosilicate. Each cohort was prohibited from exposure to the other medication. The cohorts were balanced by propensity score matching and the greedy nearest neighbor algorithm for age, race, gender, ethnicity. They were also balanced for systolic and diastolic heart failure diagnoses, and for each individual stage of CKD (1 through 5 and end stage). They were also balanced for use of ACEi, ARBs, and MRAs. This resulted in 8,921 patients in each arm. They were then evaluated for the outcomes of hospital readmission, hyperkalemia episodes (>6.1 mmol/L), and death within 12 months. Results Patients treated with patiromer were more likely to be hospitalized over the following twelve months (44% vs 40%, RR 1.11, 95% CI (1.07,1.15), p value <0.0001). They were also more likely to experience hyperkalemia (11.7% vs 9.2%, RR 1.27, 95% CI (1.16,1.38), p value <0.0001). Patiromer was also associated with slightly greater all cause mortality (27% vs 25%, RR 1.08, 95% CI (1.03,1.13), p value 0.0021). Discussion This study demonstrates patiromer has more readmissions and hyperkalemia episodes along with greater mortality. In conclusion, sodium zirconium cyclosilicate was found to have better outcomes compared to that of patiromer. Further studies are necessary to better understand the utility of using sodium zirconium cyclosilicate as maintenance therapy for hyperkalemia in order to maximize GDMT in CKD patients with heart failure.

Optimizing aldosterone receptor antagonist therapy by sodium zirconium cyclosilicate in heart failure - OPRA-HF trial

Abstract Background Heart failure remains a significant health burden, characterized by disabling symptoms and mortality rates comparable to cancer. Mineralocorticoid antagonists (MRAs), pivotal in treating heart failure with reduced ejection fraction (HFrEF), are underutilized due to concerns of hyperkalemia. Sodium Zirconium Cyclosilicate (SZC) enables optimized MRA therapy by reducing hyperkalemia. However, prospective studies on the efficacy and safety of SZC in patients with HFrEF and high hyperkalemia risk are lacking, particularly in the context of contemporary heart failure quadruple-therapy including angiotensin receptor neprilysin inhibitor (ARNI) and Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors. Purpose The OPRA-HF trial aims to assess the efficacy and safety of SZC in optimizing MRA treatment in symptomatic patients with HFrEF with risk for hyperkalemia on top of optimal guideline-directed medical therapy including ARNI and SGLT2 Inhibitors. Methods This investigator-initiated multicentred, randomized, placebo-controlled, and double-blinded trial include patients with HFrEF on suboptimal MRA treatment due to (1) history of hyperkalemia due to MRA, or (2) risk of hyperkalemia due to reduced renal function (eGFR 30-45 ml/min/m2) and current potassium 4.5-5-0 mmol/L. Patients undergo a Run-In phase with SZC, initiating or up-titrating MRA to target doses for 4-7 weeks and SZC was initiated in those patients that became hyperkalemic (K+>5 mEq/L. Those normokalemic and tolerating MRA ≥ 25 mg daily or at least 25 mg dose increase vs before run-in were randomized to SZC (5g or 10g) or placebo for 6 months. Study is powered to randomize 110 patients. Primary outcomes include maintaining daily MRA dose ≥ 25 mg or dose increase by 25 mg with normal potassium levels without rescue therapy. Secondary outcomes include evaluating the safety and tolerability of SZC as well as impact of SZC on quality of life. Results In this ongoing trial, so far 40 patients have been randomized. Of these, mean age was 74.3 years, 88.9% men. Most patients had ischemic etiology (54.2%), 36.1% had diabetes mellitus, 52.8% had hypertension.n. At screening 94.4% had beta-blockers, 35% ACEI/ARB, 60% ARNI and 72.2% had SGLT2 inhibitors, 33.3% had no MRAs and 35,6% of patients had less than 25 mg MRA daily,62,2% had 25 mg MRA daily, mean p-potassium was 4.7+0.4 mmol/L, and eGFR was 57.3 ml/min/1.73m². After run-in, 85.2% were on 50 mg MRA daily. A substantial number (51.2%) of eligible patients with previous hyperkalemia had Run-In failure as they now successfully tolerated target dose of MRA at 50 mg daily without recurrent hyperkalemia. SZC dosing was 5g once daily in 78.9% of patients. Conclusion This ongoing trial will provide evidence for the use of SZC to optimize MRA treatment in contemporary HFrEF patients. Preliminary findings suggest SZC effectively maintains normokalemia, enabling MRA optimization, potentially improving patients’ otcome.

Sodium zirconium cyclosilicate treatment and rates of emergency interventions for hyperkalaemia: a propensity-score weighted case-control study

Abstract Background Sodium zirconium cyclosilicate (SZC) reduces serum potassium in patients with chronic hyperkalaemia in clinical trials, but its role in the emergency treatment of hyperkalaemia is unproven. We hypothesised that SZC use for emergent hyperkalaemia would be associated with a reduction in rates of emergency interventions for hyperkalaemia. Methods This was a single centre, propensity-score weighted case-control study of patients admitted with hyperkalaemia to a specialist renal centre. We randomly selected 250 patients admitted between April 2021 and September 2022 (post-SZC era) with a potassium ≥ 5.5 mmol/L treated with at least one ≥ 10g dose of SZC (treatment group). We randomly selected a comparator group of 250 patients admitted between January 2018 and December 2019 (pre-SZC era) with a potassium ≥ 5.5 mmol/L (control group). Baseline demographic and clinical characteristics were recorded and used as covariates for propensity scoring (PS) and inverse probability treatment weighting (IPTW). Our primary outcome measure, rates of emergency haemodialysis, were tested using unadjusted models and multivariable logistic regression models on unweighted data in addition to unadjusted models on weighted data. We also reviewed rates of emergency temporary central venous access as a secondary outcome. Results 59% were male, the mean age was 67 (SD 14) years and 149 (30%) were receiving maintenance dialysis. IPTW achieved satisfactory balance of covariates between the treatment and control groups. In the treatment group, patients were 77% less likely to need emergency haemodialysis (OR 0.23; CI 0.17 to 0.31); this result was consistent following analysis of weighted and unweighted data. Similarly, patients treated with SZC were 73% less likely to require emergency temporary central venous access (OR 0.27; CI 0.20–0.36). Conclusion SZC was associated with signification reduction in rates of emergency haemodialysis and emergency temporary central venous access in patients admitted to a specialised renal centre with emergent hyperkalaemia.

Comparison of Sodium Zirconium Cyclosilicate to Calcium Polystyrene Sulfonate for Acute Hyperkalemia Among Hospitalized Elderly Patients

Comparison of Sodium Zirconium Cyclosilicate to Calcium Polystyrene Sulfonate for Acute Hyperkalemia Among Hospitalized Elderly Patients

Evaluation of Monotherapy Sodium Zirconium Cyclosilicate Versus Sodium Polystyrene Sulfonate for Acute Hyperkalemia: A Cohort Study.

Comparison of monotherapy sodium zirconium cyclosilicate (SZC) versus sodium polystyrene sulfonate (SPS) is lacking. We aimed to evaluate the effectiveness of SZC versus SPS for acute potassium lowering. This retrospective cohort study included hospitalized adult patients with acute hyperkalemia treated with SZC or SPS monotherapy. The primary outcome was time to normalization of serum potassium. Secondary outcomes included necessity of additional treatment, achievement of normokalemia at 1, 2, 4, 8, and 24 hours, and change in serum potassium from baseline to 1, 2, 4, 8, and 24 hours. Fifty-one patients received SZC and 50 received SPS. Mean baseline potassium was 5.4 mmol/L for both groups. Median time to normokalemia was 14 (IQR 8-20) hours in the SZC group versus 17 (IQR 10-21) hours in the SPS group (P = .26). Normokalemia was achieved at 24 hours in 80% versus 77% in each group, respectively (P = .56). Six patients per group required additional treatment (P = .97). Mean serum potassium at all time points was numerically lower with SZC, but statistical significance was only observed at hour 8 (4.6 vs 5.0 mmol/L, P = .005), which was associated with a -0.77 versus -0.51 mmol/L decrease in serum potassium from baseline in each group, respectively (P = .026). SZC monotherapy is at least as effective as SPS in treating mild hyperkalemia and may reduce serum potassium more quickly and to a greater degree than SPS. Future research in more severe hyperkalemia and with monitoring of potassium at regular intervals is needed to better understand the role and potential advantages of SZC over SPS.

Effects of 3.0 mEq/L [K+] Dialysate with Sodium Zirconium Cyclosilicate (SZC) vs. 2.0 mEq/L [K+] Dialysate without SZC on Cardiac Arrhythmia Rates

Effects of 3.0 mEq/L [K+] Dialysate with Sodium Zirconium Cyclosilicate (SZC) vs. 2.0 mEq/L [K+] Dialysate without SZC on Cardiac Arrhythmia Rates

Avoiding arrythmias by personalizing the dialysate concentration: a case for precision medicine in patients on dialysis

Cardiac arrythmias are common in patients undergoing maintenance hemodialysis (HD). In this issue of the journal, Charytan et al showed that, in HD patients with hyperkalemia (5.1 - 6.5 mEq/l), a dialysate concentration of 3 mEq/l combined with sodium zirconium cyclosilicate (SZC) on dialysis-free days is associated with a less rate of atrial fibrillation compared to a dialysate concentration of 2 mEq/l over 8 weeks. Despite the obvious limitations such as the small sample size, short treatment period and the absence of information on longer-term impact regarding patient important outcomes such as sudden death, this well-conceived pilot study provides impetus for larger prospective trials to test whether this personalized approach reduces major cardiovascular events and mortality.

Updated Design and Status of CONTINUITY: A Phase 4 Study of Continued Postdischarge Sodium Zirconium Cyclosilicate in CKD

Updated Design and Status of CONTINUITY: A Phase 4 Study of Continued Postdischarge Sodium Zirconium Cyclosilicate in CKD

Effectiveness, Safety, and Treatment Patterns of Sodium Zirconium Cyclosilicate (SZC) for Hyperkalemia (HK) in China: Final Results of the Actualize Study

Effectiveness, Safety, and Treatment Patterns of Sodium Zirconium Cyclosilicate (SZC) for Hyperkalemia (HK) in China: Final Results of the Actualize Study

Hyperkalemia-Related Health Care Resource Use (HRU) Associated with Short-Term vs. Long-Term Sodium Zirconium Cyclosilicate (SZC) Therapy in Patients with ESKD: The GALVANIZE Outcomes Study

Hyperkalemia-Related Health Care Resource Use (HRU) Associated with Short-Term vs. Long-Term Sodium Zirconium Cyclosilicate (SZC) Therapy in Patients with ESKD: The GALVANIZE Outcomes Study

Effects of Sodium Zirconium Cyclosilicate on Quality of Life in Patients Undergoing Hemodialysis with Hyperkalemia: Design and Rationale of the Y-QOL Study

Effects of Sodium Zirconium Cyclosilicate on Quality of Life in Patients Undergoing Hemodialysis with Hyperkalemia: Design and Rationale of the Y-QOL Study

Efficacy and safety analysis of sodium zirconium cyclosilicate and calcium polystyrene sulfonate on rapid reduction of potassium in moderate to severe hyperkalemia patients with chronic kidney disease without dialysis.

Hyperkalemia is a common complication of chronic kidney disease (CKD). This study aims to investigate the efficacy and safety of sodium zirconium cyclosilicate and calcium polystyrene sulfonate in reducing potassium in patients with acute and severe hyperkalemia in CKD who are not undergoing dialysis. A retrospective real-world study was conducted among 73 patients with non-dialysis chronic kidney disease who were hospitalized in the First Affiliated Hospital of Chengdu Medical College from June 2020 to June 2022. 33 patients treated with sodium zirconium cyclosilicate were categorized as SZC group, and the other 40 patients treated with calcium polystyrene sulfonate were categorized as CPS group. Serum potassium, serum sodium, magnesium, calcium, and phosphorus levels were examined. Adverse reactions were recorded during medication. Significantly decreased serum potassium was observed in both groups, whereas the potassium reduction was higher in the SZC group than in the CPS group at 2, 4, 24, and 48 hours after medication while there was no statistically significant difference in the serum potassium level between the two groups at 72 hours. For those people whose initial potassium exceeded 6 mmol/L, the potassium reduction was more obvious in the SZC group than in the CPS group at 2 and 4 hours after medication. The control rate of hyperkalemia in the SZC group was significantly higher than in the CPS group at 4, 24, and 48 hours. No distinct change was observed in serum sodium, calcium, magnesium, and phosphorus before and 72 hours after medication. No severe adverse reactions occurred. Sodium zirconium cyclosilicate has a more obvious effect on reducing potassium particularly for those patients with moderate to severe hyperkalemia who need rapid potassium reduction.

Effects of dialysate potassium concentration of 3.0mEq/l with sodium zirconium cyclosilicate on dialysis-free days versus dialysate potassium concentration of 2.0mEq/l alone on rates of cardiac arrhythmias in hemodialysis patients with hyperkalemia

The optimal approach towards managing serum potassium and hemodialysate potassium concentrations is uncertain. To study this, adults receiving hemodialysis for three months or more with hyperkalemia (pre-dialysis serum potassium (sK+) 5.1-6.5 mEq/l) had cardiac monitors implanted and were randomized to either eight weeks of 2.0 potassium/2.5 calcium mEq/l dialysate without sodium zirconium cyclosilicate (SZC) (2.0 potassium/noSZC) or 3.0 potassium/2.5 calcium mEq/l dialysate combined with SZC (3.0 potassium/SZC) on non-dialysis days to maintain pre-dialysis sK+ 4.0-5.5 mEq/l, followed by treatment crossover for another eight weeks. The primary outcome was the rate of adjudicated atrial fibrillation (AF) episodes of 2 minutes or more duration. Secondary outcomes included clinically significant arrhythmias (bradycardia, ventricular tachycardia, and/or asystole) and the proportion of sK+ measurements within an optimal window of 4.0-5.5 mEq/l. Among 88 participants (mean age: 57.1 years; 51% male; mean pre-dialysis sK+: 5.5 mmol/l) with 25.5 person-years of follow-up, 296 AF episodes were detected in nine patients. The unadjusted AF rate was lower with 3.0 potassium/SZC versus 2.0 potassium/noSZC; 9.7 vs. 13.4/person-year (modeled rate ratio 0.52; 95% confidence interval: 0.41; 0.65). Clinically significant arrhythmias were reduced with 3.0 potassium/SZC vs. 2.0 potassium/noSZC 6.8 vs. 10.2/person-year modeled rate ratio 0.47: 0.38;0.58). Fewer sK+ measurements outside the optimal window occurred with 3.0 potassium/SZC (modeled odds ratio: 0.27:0.12, 0.35). Hypokalemia was less frequent (33 vs. 58 patients) with 3.0 potassium/SZC compared with 2.0 potassium/noSZC. Thus, in patients with hyperkalemia on maintenance hemodialysis, a combination of potassium 3.0 mEq/l and SZC on non-hemodialysis days reduced the rates of AF, other clinically significant arrhythmias, and post-dialysis hypokalemia compared with potassium 2.0/noSZC.

Hyperkalemia burden and treatment patterns in Chinese patients on hemodialysis: final analysis of a prospective multicenter cohort study (PRECEDE-K)

Objectives Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are at risk for hyperkalemia (HK), associated with cardiac arrhythmia and sudden death. Data on the burden of HK and management techniques among HD patients in China are still scarce. This study assessed the treatment modalities, recurrence, and prevalence of HK in Chinese HD patients. Methods In this prospective cohort study conducted from May 2021 to July 2022, patients aged ≥18 years who had ESRD and were on HD were enrolled from 15 centers in China (up to 6 months). Results Overall, 600 patients were enrolled. At the baseline visit, mean (± standard deviation) urea reduction ratio was 68.0% ± 9.70 and Kt/V was 1.45 ± 0.496. Over 6 months, 453 (75.5%) patients experienced HK, of whom 356 (78.6%) recurred. Within 1, 2, 3, 4, 5, and 6 months, 203 (44.8%), 262 (57.8%), 300 (66.2%), 326 (72.0%), 347 (76.6%), and 356 (78.6%) patients had at least one HK recurrence event, respectively. The proportions of patients with ≥1, 2, 3, 4, 5, or 6 HK recurrence events were 356 (78.6%), 306 (67.5%), 250 (55.2%), 208 (45.9%), 161 (35.5%), and 110 (24.3%), respectively. Among the 453 patients who experienced HK, only 24 (5.3%) were treated with potassium binders: seven (1.5%) with sodium polystyrene sulfonate, 13 (2.9%) with calcium polystyrene sulfonate, and six (1.3%) with sodium zirconium cyclosilicate. Conclusion Since HK is a chronic illness, long-term care is necessary. Patients on HD should have effective potassium management on non-dialysis days, yet our real-world population rarely used potassium binders. Trial registration ClinicalTrials.gov Identifier NCT04799067

Novel Potassium Binders for Early Postoperative Hyperkalemia in Kidney Transplant Recipients: A Single-Center Experience

PurposeEvaluate the safety/efficacy of novel potassium binders (patiromer, sodium zirconium cyclosilicate [SZ-9]) for early postoperative hyperkalemia following kidney transplantation. MethodsRetrospective, single-center, cohort study of deceased-donor kidney recipients transplanted between 1/2018 and 12/2020. Potassium-binder use was evaluated from immediately posttransplant until discharge. Potassium binders were administered ≥2 hours before/after medications. ResultsA total of 179 patients were included, 24 (13%) of whom received potassium binders (16 [67%] patiromer, 7 [29%] SZ-9, 1 [4%] both) for a mean of 2.5 (±3.18) doses. Peak potassium levels were higher in the potassium-binder group (6.05 vs 5.35 mEq/L; P < .001). More patients on potassium binders transitioned to atovaquone than those on no binders (n = 21 [100%] vs n = 112 [75%], respectively; P = .005). Delayed graft function (DGF) was observed in 100 (56%) patients, with a higher proportion receiving potassium binders (18 [75%] vs 82 [53%], respectively; P = .042). There was no difference between groups in number of posttransplant dialysis sessions required in the general study population (P = .2), nor in the DGF group (P = .12). No difference was noted in the incidence of ileus (P = .2), or gastrointestinal symptoms (diarrhea, nausea, vomiting; P = .6). Of the 24 patients who received inpatient binders, 9 (37.5%) were discharged and remained on them for a mean of 46 (±49) days. ConclusionPatiromer and SZ-9 appear safe in the early posttransplant period, but larger prospective trials are needed. Potassium-binder use does not appear to be associated with fewer dialysis sessions in DGF patients, however, they may be used as additional tools for lowering potassium in these patients.

Risk of Serious Adverse Gastrointestinal Events with Potassium Binders in Hospitalized Patients: A National Study.

Concerns about serious adverse gastrointestinal (GI) events with sodium polystyrene sulfonate (SPS) led to development of two new potassium binders, patiromer and sodium zirconium cyclosilicate (SZC), for treatment of hyperkalemia. To compare risk of intestinal ischemia/thrombosis or other serious GI events associated with SPS, patiromer, or SZC in hospitalized patients. Retrospective cohort study. National sample of 3,144,960 veterans hospitalized 2016-2022 in the U.S. Department of Veterans Affairs Healthcare System. Demographics, comorbidities, medications and outcomes were ascertained from the VA Corporate Data Warehouse. Exposures were SPS, patiromer, SZC. Outcomes were 30-day intestinal ischemia/thrombosis, and a composite of intestinal ischemia/thrombosis, peptic ulcer/perforation or bowel resection/ostomy. Potassium binders were used during 39,270 (1.3%) hospitalizations: SPS = 30,040 (1.0%), patiromer = 3,750 (0.1%), and SZC = 5,520 (0.2%). Intestinal ischemia/thrombosis occurred with 106/30,040 (0.4%) SPS, 12/3750 (0.3%) patiromer and 24/5520 (0.4%) SZC, vs. 6998/3,105,650 (0.2%) without potassium binder. Adjusted odds ratios (aOR) were 1.40 [95% CI, 1.16 to 1.69] with SPS, 1.36 [CI, 0.79 to 2.36] with patiromer, and 1.78 [CI, 1.21 to 2.63] with SZC exposures. Composite GI adverse events occurred with 754/30,040 (2.5%) SPS, 96/3750 (2.6%) patiromer, 2.6% SZC, vs. 144/5520 (2.4%) without binder; aOR were 1.00 [CI, 0.94 to 1.08] with SPS, 1.08 [CI, 0.89 to 1.32] with patiromer, and 1.08 [CI, 0.93 to 1.27] with SZC exposures. No statistical difference in intestinal ischemia/thrombosis between each new agent and SPS was seen (p = 0.274 for SPS vs. SZC; p = 0.916 for SPS vs. patiromer). Risk of intestinal ischemia/thrombosis or other serious adverse GI events was low and did not differ across three potassium-binding drugs.

Plant-based diet in hyperkalemic chronic kidney disease patients receiving sodium zirconium cyclosilicate: a feasibility clinical trial

BackgroundPlant-based diets (PBD) may induce hyperkalemia in chronic kidney disease (CKD) patients. ObjectivesWe explored the safety and feasibility of PBD in hyperkalemic CKD patients receiving the potassium binder sodium zirconium cyclosilicate (SZC). MethodsIn the current 6-wk trial, 26 hyperkalemic patients with CKD stage 4–5 not on dialysis received a low-protein low-potassium diet plus SZC for 3 wk and then a PBD with high potassium content delivered as a weekly food basket while continuing SZC for subsequent 3 wk. Plasma potassium was monitored weekly and SZC was titrated to achieve normokalemia. The 24-h urine excretion of potassium and sodium, 24-h food records, dietary quality, nutritional status, Bristol stool scale, Quality of life (QoL), and renal treatment satisfaction were assessed at baseline (week 0), week 3, and week 6. ResultsMean plasma potassium decreased from 5.5 to 4.4 mEq/L within 48–72 h after baseline, then rose to 4.7–5.0 mEq/L throughout the remaining study period following dose adjustments of SZC that matched the increased potassium intake of PBD from week 3 to week 6. Over the study period, 24-h urinary potassium excretion decreased from week 0 to week 3 and increased from week 3 to week 6. During the study, 58% of patients had fasting plasma potassium between 3.5 and 5.0 mEq/L and there was no episode of plasma potassium >6.5 mEq/L or <3.0 mEq/L during the study. P-carbon dioxide increased from baseline until week 6 (21 ± 2 to 23 ± 2 mEq/L; P = 0.002; mean ± SD), whereas remaining laboratory values remained unchanged. Fiber intake, dietary quality, the domain physical functioning from QoL, and 1 question of renal treatment satisfaction improved, whereas stool type and frequency did not change after starting PBD. ConclusionsPBD in hyperkalemia-prone CKD patients receiving SZC improved dietary quality and increased the intake of healthy foods, whereas plasma potassium concentration remained stable within normal values for most patients. Trial registration numberThis trial was registered at the https://clinicaltrials.gov/study/NCT04207203 as NCT04207203.