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In this double-blind trial, patients with chronic kidney disease and type 2 diabetes were randomly assigned to receive the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone or placebo. Treatment with finerenone resulted in lower risks of chronic kidney disease outcomes and cardiovascular outcomes than placebo.

Hyperkalemia contributes to significant mortality and limits the use of cardioprotective and renoprotective renin–angiotensin–aldosterone blockers. Current therapies are poorly tolerated and not always effective. Here we conducted a phase 2 randomized, double-blind, placebo-controlled dose-escalation study to assess safety and efficacy of ZS-9. This oral selective cation exchanger that preferentially entraps potassium in the gastrointestinal tract was given to patients with stable Stage 3 chronic kidney disease and hyperkalemia (5.0 to 6.0 mEq/l) during a 2-day period. Of 90 eligible patients with mean baseline serum potassium of 5.1 mEq/l, 30 were randomized to placebo, 12–0.3 g, 24–3 g, or 24 to 10 g of ZS-9 three times daily for 2 days with regular meals. None withdrew and ZS-9 dose-dependently reduced serum potassium. The primary efficacy end point (rate of serum potassium decline in the first 48 h) was met with significance in the 3- and 10-g cohorts. From baseline, mean serum potassium was significantly decreased by 0.92±0.52 mEq/l at 38 h. Urinary potassium excretion significantly decreased with 10-g ZS-9 as compared to placebo at day 2 (+15.8 +/- 21.8 vs. +8.9 +/- 22.9 mEq per 24h) from placebo at day 2. In this short-term study, no serious adverse events were reported; only mild constipation in the 3-g dose group was possibly related to treatment. Thus, ZS-9 was well-tolerated in patients with stable chronic kidney disease and hyperkalemia leading to a rapid, sustained reduction in serum potassium.

In this trial, patients with type 2 diabetes had a lower incidence of major cardiovascular outcomes with a systolic blood-pressure target of less than 120 mm Hg than with a target of less than 140 mm Hg.

Background The objectives of this phase two study are to investigate the efficacy of two starting doses of 8.4 g and 16.8 g and evaluate the long-term safety of patiromer in Japanese patients with hyperkalemia. Methods This study comprised three cohorts; non-dialysis patients with baseline serum potassium (sK) level of 5.1 to < 6.0 mmol/L (NDC1); 6.0 to < 6.5 mmol/L (NDC2); dialysis patients with baseline sK level of 5.5 to < 6.5 mmol/L (DC). The study design was one-week, randomized, double-blind, placebo-controlled, and open label extension for one year in NDC1, open label during the study in NDC2 and DC. Patients were randomly assigned to patiromer 8.4 g, 16.8 g or placebo in NDC1, 8.4 g or 16.8 g in NDC2 and DC. Dose was adjusted up to 25.2 g according to the titration algorism in open label period. Results A total of 185 patients were randomized (NDC1:153, NDC2:10, and DC:22). The primary endpoint of the change in least squares mean sK levels at Week 1 in NDC1 was  – 0.55,  – 0.77 and  – 0.10 mmol/L for the 8.4 g, 16.8 g and placebo group ( P  < 0.001 for the patiromer group vs the placebo group). In all cohorts for each patiromer group, more than 80% of patients achieved normal sK at Week 5. There was no severe treatment-related adverse event. Conclusion Treatment with patiromer was effective in lowering and maintaining target sK levels, also well tolerated for one year in Japanese patients with hyperkalemia.

Background Finerenone is a nonsteroidal selective mineralocorticoid receptor antagonist (MRA) that demonstrated efficacy in delaying the progression of chronic kidney disease (CKD) and reducing cardiovascular events in patients with CKD and type 2 diabetes mellitus in FIDELIO-DKD, where 5734 patients were randomized 1:1 to receive either finerenone or placebo, with a median follow-up of 2.6 years. Doses of finerenone 10 or 20 mg once daily were titrated based on (serum) potassium and estimated glomerular filtration rate. The MRA mode of action increases potassium. Methods Nonlinear mixed-effects population pharmacokinetic/pharmacodynamic models were used to analyze the finerenone dose–exposure–response relationship for potassium in FIDELIO-DKD. Individual time-varying exposures from pharmacokinetic analyses were related to the potassium response via a maximal effect, indirect-response model informed by 148,384 serum potassium measurements. Results Although observed potassium levels decreased with increasing dose (i.e., inverse relation), model-based simulations for a fixed-dose setting (i.e., no dose titration) revealed the intrinsic finerenone dose–exposure–potassium response, with potassium levels increasing in a dose- and exposure-dependent manner, thus explaining the apparent conflict. The potassium limit for inclusion and uptitration from finerenone 10 to 20 mg in FIDELIO-DKD was ≤ 4.8 mmol/L. Modified limits of ≤ 5.0 mmol/L were simulated, resulting in higher hyperkalemia frequencies for both the finerenone and the placebo arms, whereas the relative hyperkalemia risk of a finerenone treatment compared with placebo did not increase. Conclusions The analyses demonstrated the effectiveness of finerenone dose titration in managing serum potassium and provide a quantitative basis to guide safe clinical use.

Hyperkalemia is common in chronic kidney disease or heart failure, especially in patients receiving RAAS inhibitors. This study showed that sodium zirconium cyclosilicate (ZS-9), a highly selective cation exchanger, induces and maintains normokalemia. Hyperkalemia (serum potassium level, >5.0 mmol per liter) is a common electrolyte disorder that is associated with serious cardiac dysrhythmias and increased mortality. 1 – 3 Patients with renal dysfunction and those with diabetes are at increased risk for hyperkalemia. 3 Therapies that inhibit the renin–angiotensin–aldosterone system (RAAS) are associated with hyperkalemia in patients with kidney disease or heart failure, 4 , 5 despite strong evidence that such therapy is beneficial in proteinuric chronic kidney disease, 6 – 9 diabetic nephropathy, 10 – 12 and systolic heart failure. 12 – 15 The use of existing polymer resins (e.g., sodium polystyrene sulfonate) has a poor side-effect profile and uncertain efficacy. Thus, there . . .

In a multicenter placebo-controlled study, patiromer, a nonabsorbable potassium binder, led to a reduction in serum potassium levels in patients with chronic kidney disease and hyperkalemia who were receiving renin–angiotensin–aldosterone system (RAAS) inhibitors. Hyperkalemia is associated with life-threatening cardiac arrhythmias and increased mortality. 1 Patients at the highest risk for hyperkalemia are those with stage 3 or higher chronic kidney disease, with or without diabetes or heart failure, who are being treated with drugs that inhibit renal potassium excretion, particularly inhibitors of the renin–angiotensin–aldosterone system (RAAS). 1 – 4 Outpatient treatment of hyperkalemia is limited by the lack of effective agents. 4 Sodium polystyrene sulfonate and calcium polystyrene sulfonate may cause serious gastrointestinal adverse events 5 – 8 as well as less serious gastrointestinal side effects that may be difficult for patients to tolerate, which together typically limit their . . .

•It seems VA implemented findings into practice immediately after trial showed harm.•Overall, there was a 30% relative decrease in combination therapy use at six months.•We observed a sustained reduction in combination therapy for eighteen months.•The same pattern emerged within each subgroup.•VA communication policies may be a model for other healthcare organizations. It takes 17 years, on average, for trial results to be implemented into practice. Using data from the Department of Veterans Affairs (VA), this study assessed the potential impact on clinical practice of the dissemination of findings from a randomized, controlled trial reporting harm with the use of combination therapy. Communication between research and VA Pharmacy Benefits Management Services (PBM)  provided the impetus for communication from the PBM about the findings of the trial in accordance with policy. In this de-implementation study, interrupted time series analysis was used for assessing prescribing patterns and adverse clinical events before and after the dissemination of the trial findings. The de-implementation strategy was multicomponent and multilevel. Strategies were aligned with categories outlined in the Expert Recommendations for Implementing Change: train and educate stakeholders, use evaluative and iterative strategies, develop stakeholder inter-relationships, change infrastructure, provide interactive assistance, and engage consumers. VA patients with type 2 diabetes mellitus, chronic kidney disease stages 1 to 3, and a moderate or severe albuminuria who received care between July 2008 and November 2017 were included. Patients were subgrouped according to treatment with an angiotensin-converting enzyme inhibitor + angiotensin receptor blocker. The primary end point was the prevalence of combination therapy use. Secondary end points were the incidences of acute kidney injury and hyperkalemia. This study followed 712,245 patients, 9297 of whom used combination therapy. Data were available from 428,535 and 283,710 patients pre- and post-intervention, respectively; among these, 8324 and 973 patients used combination therapy, the median ages were 66 and 68 years, and 96.92% and 98.82% were men. One month following communication from the PBM, the reductions in combination therapy users, acute kidney injury events, and hyperkalemia were 331.94 (95% CI, 500.27–163.32), 36.58% (95% CI, 31.90%–41.95%), and 25.49% (95% CI, 14.17%–36.07%) per 100,000 patients per month, respectively (all, P < 0.001), whereas before the communication, these changes were +14.84 (95% CI, 10.27–19.42), –3.46% (95% CI, 3.18–3.74), and –3.27% (95% CI, 2.66%–3.87%) (all, P < 0.001). The apparent speed and impact of the implementation of changes resulting from the dissemination of trial findings into VA clinical practice are encouraging. The speed of implementation was much faster than average for health care providers in the United States. Established communications between research and clinical practice, as well as established policy and communications between PBM and clinical practice, may be a model for other health care organizations. [Display omitted]

Patients undergoing hemodialysis (HD) face severe dietary potassium restrictions, reducing their quality of life (QOL) and potentially worsening their prognosis. Sodium zirconium cyclosilicate (SZC) is a novel selective potassium binder that lowers potassium levels, with minimal effects on other electrolytes. The Y-QOL study will evaluate whether SZC can improve QOL by easing the burden of dietary restrictions. This 8-week, multicenter, randomized, parallel-group, open-label trial will enroll 200 outpatients with hyperkalemia (potassium level 5.5–6.4 mEq/L after a 2-day inter-dialytic interval) on thrice-weekly HD. Participants will be randomized to receive SZC (starting dose 5 g on non-dialysis days, adjustable to 15 g based on serum potassium levels) plus dietary guidance, or dietary guidance alone to maintain serum potassium levels at 4.0–5.4 mEq/L. The primary endpoint is changes in The 7-item QOL Disease-specific Impact Scale (QDIS-7) scores at week 8 from baseline. Secondary endpoints include additional QOL scores, nutritional status, inflammation markers, Bristol Stool Form Scale, serum potassium reduction, and safety. Recruitment began on January 24, 2024, and the study will conclude on March 31, 2026. The Y-QOL study aims to determine the effectiveness of SZC in improving QOL by reducing serum potassium levels in patients with hyperkalemia undergoing HD. Trial registration Registered Report Identifier: jRCT 031230404. Date of registration; January 15, 2024.

Objective HyperkalemiaF is associated with fatal cardiac arrhythmias, all-cause mortality, and frequent emergency department visits among patients with hyperkalemia. A recent Chinese epidemiological study suggested that the severity of hyperkalemia increases with comorbidities. Diagnosis, testing, and overall management of patients with hyperkalemia in the emergency department require strengthening. However, the lack of evidence from the emergency department and consensus guidelines has led to poorly characterized treatment patterns for hyperkalemia. The present study will evaluate the real-world effectiveness of different treatment options among patients with hyperkalemia in the emergency department across China. Methods This multicenter, prospective, observational study plans to collect primary data from 600 patients diagnosed with hyperkalemia who present to the emergency department in 15–20 tertiary hospitals across China. Patients aged ≥18 years with serum potassium levels ≥5.5 mmol/L will be included. Patients previously enrolled in any other clinical study within 3 months before enrollment will be excluded. Eligible patients will be enrolled, assessed at baseline, and followed up until discharge from the emergency department or death. The primary objective will be to determine the real-world effectiveness of potassium-lowering treatment (monotherapy/combination therapy), calculated as the mean change in serum potassium levels from baseline to 5 ± 1 h after treatment initiation. The secondary objectives will assess the clinical burden, calculated as the number of patients with baseline serum potassium levels ((5.5, 6.0), (6.0, 6.5), (6.5, 7.0), and (≥7.0) mmol/L), real-world treatment patterns, serum potassium testing, and the duration between baseline testing and treatment initiation. Exploratory objectives will further evaluate clinical outcomes among patients with different baseline serum potassium levels as described above and the proportion of patients recovering to normal serum potassium levels. Discussion The POETRY-E study is the first prospective observational study to evaluate the real-world effectiveness of different potassium-lowering treatment regimens among patients with hyperkalemia in the Chinese emergency department setting. This study addresses the overall burden and management among patients with hyperkalemia in China. Trial registration: Name of the Registry: Chinese Clinical Trial Registry Registration Number: ChiCTR2100053100