Establishing Cross-Specialty Expert Consensus on the Optimal Management of Hyperkalemia in Patients With Heart Failure and Chronic Kidney Disease

Abstract

Background: Patients with both heart failure (HF) and chronic kidney disease (CKD) are often treated with renin-angiotensin-aldosterone system inhibitors (RAASi), but these drugs can cause hyperkalemia, which may lead to their reduction or discontinuation, resulting in the loss of their beneficial effects. Approaches to managing RAASi-induced hyperkalemia are discordant, so in this study we aimed to establish a cross-specialty consensus on the optimal approach to managing hyperkalemia in patients with HF and CKD.

Methods and Results: The study used a modified Delphi methodology. A steering committee of Japanese cardiologists and nephrologists drafted 26 consensus statements, which were used to create a survey, distributed across Japan. A total of 250 responses were received. Consensus, defined as 75% agreement, was achieved for 21/26 (81%) statements. Respondents agreed on the importance of effective hyperkalemia management based on serum potassium levels and supported the use of potassium binders (PBs), particularly novel PBs such as sodium zirconium cyclosilicate, to treat hyperkalemia while maintaining RAASi therapy. However, when potassium levels exceed 6.0 mEq/L, reduction or discontinuation of RAASi may be considered based on individual risk factors.

Conclusions: This consensus provides proposals that may help support the optimal management of RAASi-induced hyperkalemia in Japanese patients with HF and CKD. It highlights the importance of treating hyperkalemia alongside optimal RAASi therapy.

Heart failure (HF) and chronic kidney disease (CKD) are globally burdensome diseases, and are often concomitant. Approximately 13% of the Japanese population are believed to have CKD,¹ and between 2.2% and 6.5% have HF.² Patients with either HF or CKD are at risk of developing cardiorenal syndrome, whereby disorders in one organ can lead to chronic or acute impairments in the other.³ Patients with cardiorenal syndrome, with both HF and CKD, are at an increased risk of developing hyperkalemia,⁴ but this risk is higher in patients with CKD, especially severe CKD, due to reduced renal excretory function.⁵ The risk is compounded when using renin-angiotensin-aldosterone system inhibitors (RAASi),⁶ which are a key part of guideline-directed medical therapy (GDMT) in treating patients with HF and CKD.⁷ Hyperkalemia is associated with significant long-term health and economic burdens, causing increased hospitalizations and higher mortality rates.^4,6

Decisions regarding hyperkalemia management can be difficult and currently there is not a universally accepted definition of hyperkalemia severity.⁸ Current guidelines state that hyperkalemia should not be a barrier to RAASi therapy, due to the loss of cardiorenal protection.^8–10 However, patients with HF and CKD often have their RAASi medication down-titrated or ceased after developing hyperkalemia. This may be understandable in cases of severe acute hyperkalemia, but discontinuing RAASi therapy has been demonstrated to lead to increased deaths, especially in patients with HF and CKD.^11,12 Japanese research found that only 27% of patients managed to achieve >50% of the guideline-recommended RAASi dose before developing hyperkalemia, with approximately one-third of patients having their RAASi discontinued as a result.¹³

Guidelines suggest using potassium binders (PBs) in patients with mild–moderate hyperkalemia to help prevent any interruption of RAASi therapy.^9,14 PBs can enable patients to reach the maximal dose of their disease-modifying therapies.^8,12 Management of HF and CKD requires close coordination between cardiologists and nephrologists to ensure patients receive optimal care. Multidisciplinary management of HF has been shown to reduce all-cause hospitalizations and medical costs.¹⁵ In Japan, research indicates discrepancies in the collaborative management of patients across primary and secondary care, with information sharing and clinician education proving particularly problematic.¹⁶

There is a large unmet need for dose attainment of RAASi therapy, and for increased awareness of guideline recommendations for hyperkalemia treatment.¹³ There is also a need to address clinical inertia in titrating therapies for patients with HF and CKD.¹⁷ The aim of this study was to establish a cross-specialty consensus on the optimal management of hyperkalemia in patients with HF and CKD in Japan. A modified Delphi method was chosen because consensus from a group of experts using formal methods is recognized as being more reliable than individual opinions.¹⁸ This modified Delphi methodology has been used successfully to explore the optimal management of hyperkalemia internationally.^8,19,20

Methods

The process followed a modified Delphi methodology (Figure 1), guided by an independent Delphi facilitator (Triducive Partners Limited). The study was not registered, and all reporting followed the ACCORD guidelines.²¹

Figure 1.

Design of the modified Delphi study.

Study Development

In February 2024, a literature review on hyperkalemia management in patients with HF and CKD was performed on PubMed and Google Scholar. Search terms included, but were not limited to, hyperkalemia management, and hyperkalemia in cardiorenal syndrome. The review focused on literature from the past 5 years. Searches were repeated with “Japan” for country-specific literature. Results were used to develop the scope and aims of the research and to create a briefing package for the steering committee (SC).

First SC Meeting and Statement Development

The SC, comprising 6 experienced consultant cardiologists and nephrologists, convened online in April 2024 to discuss hyperkalemia management in patients with HF and CKD. The SC was selected based on published research, experience in hyperkalemia management, and engagement with developing cardiology or nephrology guidelines. This number of specialists is within the accepted range for reliability of Delphi SCs.²² Based on the literature review, the group agreed on 4 main topics of focus: (1) risk factors and risk stratification for managing hyperkalemia in patients with HF and CKD; (2) prevention of hyperkalemia for at-risk patients with HF and CKD; (3) correction of hyperkalemia for at-risk patients with HF and CKD using of potassium-lowering therapy; and (4) cross-specialty alignment (Cardiology & Nephrology).

These topics were discussed in detail. The SC worked collaboratively to develop 26 draft consensus statements. Statements from previous Delphi research into hyperkalemia management were reviewed and helped inform the current project.^8,19 Drafted statements were collated and independently rated as either “accept”, “remove”, or “reword” by the SC following the meeting. The group was able to suggest additional statements and provide qualitative feedback. The draft statements underwent 3 rounds of independent SC ratification. The facilitator actioned changes at each stage.

Survey Development

The resulting 26 statements were used to create a Likert survey, for distribution by a third party (M3) to a wider panel of Japanese clinicians. The survey was fully translated in Japanese (a copy of the translated statements is presented in the Supplementary Information).

The survey presented each statement alongside a 4-point Likert scale (‘strongly disagree’, ‘tend to disagree’, ‘tend to agree’, and ‘strongly agree’) to allow respondents to indicate their level of agreement. Stopping criteria were established as a 3-week response window, a target of 250 responses, and 80% of statements passing the consensus threshold, which was set at 75% (a widely accepted level²³). Consensus was then defined as ‘strong’ at 75% or greater and ‘very strong’ at 90% or greater. These criteria were established to gain the required number of responses while accounting for time pressures faced by clinicians. Following standard Delphi methodology, the survey was quantitative and did not seek respondent feedback.^8,19

Survey Respondents

All respondents were screened and had to be a board-certified cardiologist or nephrologist in Japan, with ≥2 years of experience, and membership of a professional society in their field (e.g., Japanese Circulation Society or Japanese Society of Nephrology). Participants with diverse academic and professional backgrounds were involved to ensure a comprehensive range of perspectives were considered. The survey was piloted with 10% of the respondent target, and no concerns were raised. All responses were subject to pattern recognition testing, and the survey had a minimum time to completion of 2.5 min to ensure genuine engagement. Survey respondents were paid a nominal fee by the third party for completing the survey.

Anonymity of responders was planned into the study design. The survey captured some demographic data for analysis, but no personal information. The identity of respondents was not known to the SC or independent facilitator. A statement of consent was included at the start of the survey and consent was implied by completion. The study did not require ethical approval as it did not fall under research in the Life and Medical Guidelines (PHRF-IRB Serial No. 24F0007).

Results Analysis and Second SC Meeting

Completed surveys were analyzed by the facilitator to produce an agreement score for each statement. Results were reviewed by the SC during the final round of the process, at an online meeting in July 2024. The SC discussed the consensus levels achieved and agreed the stopping criteria had been fulfilled. Based on the statements with the highest agreement, the SC developed a set of proposals for optimal practice. These were independently ratified by the SC as part of the manuscript review process.

Results

Statement Ratification

The 26 draft statements were critically reviewed by the SC. After 2 rounds of review, 6 statements were removed, and 6 new statements were added. All statements underwent minor linguistic editing. During the third round of review, the SC approved all statements without amendments. The approved statements were then translated and used in the survey.

Responder Demographics

A total of 250 survey responses were received from cardiologists (n=125) and nephrologists (n=125). Most respondents had ≥20 years of experience in their role (n=114), followed by 11–20 years (n=90), 6–10 years (n=32), and 2–5 years (n=14). All responders were members of the Japanese Circulation Society or Japanese Society of Nephrology.

Overall Agreement Levels

Results showed very strong agreement (≥90%) for 18 (69%) statements, and strong agreement (<90% and ≥75%) for 3 (12%) statements; 5 (19%) statements failed to achieve consensus due to the inclusion of grouped statements to test the serum potassium level at which clinicians believed RAASi use should be stopped or downtitrated, vs. the levels at which they agreed RAASi could be continued.

The overall levels of agreement are illustrated in Figure 2. Within the Table, the results of the current study are compared with those from the European and North American Delphi consensus process conducted by Burton et al.⁸ and the Chinese Delphi consensus by Zhao et al.¹⁹ Distribution of consensus scores across the Likert scale is presented in Supplementary Figure 1.

Figure 2.

Consensus agreement levels by statement. The threshold for consensus is depicted by the orange line (75%). The blue line signifies the threshold for very strong agreement (90%).

Table.

Consensus Statements and Corresponding Levels of Agreement* in the Current Study and How These Compare With Statements From Previous Research in Europe–North America, and China

Statement no.	Statement	% Agreement
		Japan					EU & Nth America	China
		Strongly Disagree	Disagree	Agree	Strongly Agree	Mean agreement
Topic A: Risk factors and risk stratification for managing hyperkalemia in patients with cardiorenal syndrome
1	Optimizing RAASi treatment provides better clinical outcomes for patients	0%	0%	22%	78%	100%	98%	97%
2	CKD, HF, and DM are diseases that increase the risk of developing hyperkalemia	0%	2%	30%	68%	98%	97%	97%
3	RAASi treatment is a risk factor for hyperkalemia	0%	3%	39%	58%	97%	94%	95%
4	Hyperkalemia is a known and manageable side effect of RAASi treatment	0%	4%	54%	43%	96%	93%	–
5	Appropriate management of hyperkalemia in patients with CKD and HF (cardiorenal patients) leads to optimization of RAASi treatment, which in turn improves cardiovascular, renal, and life prognosis	0%	0%	33%	66%	100%	90%	–
6	Hyperkalemia associated with RAASi treatment should be recognized as a predictable, treatable, and manageable side effect, even in patients with a history of hyperkalemia or at high-risk for developing hyperkalemia	0%	8%	53%	39%	92%	96%	96%
7	Hyperkalemia is associated with discontinuation or de-escalation of RAASi therapy	6%	21%	38%	34%	72%	84%	97%
8	In patients with CKD and HF (cardiorenal patients), when mild (5.0<K+≤5.5) hyperkalemia is present, treatment of hyperkalemia should be prioritized, and RAASi should be continued without reduction in dose, taking into account their cardioprotective effects	2%	10%	47%	40%	88%	91%	79%
9	In patients with CKD and HF (cardiorenal patients), when moderate (5.5<K+≤6.0) hyperkalemia is present, treatment of hyperkalemia should be prioritized, and RAASi should be continued without reduction in dose, taking into account their cardioprotective effects	6%	28%	46%	20%	66%	–	–
10	In patients with CKD and HF (cardiorenal patients), when severe (6.0<K+≤6.5) hyperkalemia is present, treatment of hyperkalemia should be prioritized, and RAASi should be continued without reduction in dose, taking into account their cardioprotective effects	30%	32%	25%	13%	38%	–	–
11	In patients with CKD and HF (cardiorenal patients), if the patient has severe hyperkalemia with a serum potassium levels above 6.5 (K+>6.5), treatment of hyperkalemia should be prioritized, and RAASi should be continued without reducing the dose, taking into account their cardioprotective effects	49%	25%	17%	9%	26%	–	–
Topic B: Prevention of hyperkalemia for at-risk cardiorenal syndrome
12	For those patients who have a known history of hyperkalemia preventing optimization of RAASi treatment, a novel PB such as SZC can be used to enable RAASi optimization	0%	6%	56%	38%	94%	92%	98%
13	Non-disease-modifying therapies that cause hyperkalemia should be avoided in patients at high-risk of hyperkalemia, e.g., NSAIDs, vegetable-based supplement	0%	3%	50%	46%	97%	94%	–
14	The necessity and effectiveness of A low K+ diet should be explained to high-risk hyperkalemia patients undergoing RAASi treatment	0%	6%	42%	53%	94%	–	96%
15	A low K+ diet is often advised to help manage K+ levels, with no/little evidence to support, and is counter to a healthy diet that is beneficial to patients with CKD and HF (cardiorenal patients)	2%	18%	60%	21%	81%	80%	84%
16	For patients for whom a low K+ diet is not appropriate or desirable, the use of a novel PB such as SZC may allow for a balanced diet	1%	8%	61%	30%	91%	91%	–
17	Patients with CKD and HF (cardiorenal patients) should have their K+ levels tested at least every 3 months or more according to disease severity	0%	1%	28%	71%	99%	–	89%
Topic C: Correction of hyperkalemia for at-risk cardiorenal syndrome with the potassium-lowering therapy
18	Discontinuation or reduction of RAASi treatment worsens cardiovascular and renal prognosis in patients with CKD and HF (cardiorenal patients)	0%	3%	44%	52%	96%	94%	–
19	Permanent discontinuation of a RAASi treatment should only be considered as a last resort strategy for uncontrollable hyperkalemia	1%	10%	52%	38%	89%	92%	75%
20	A novel PB such as SZC enables guideline- recommended RAASi dosing and the proven benefits that this brings to patients	0%	4%	53%	43%	96%	92%	97%
21	Before discontinuing or reducing the dose of RAASi treatment, optimal hyperkalemia management, including the initiation of a novel PB such as SZC, should be utilized or at least considered	0%	8%	48%	43%	91%	92%	88%
22	SPS and CPS should not be used in the medium- or long-term as it may cause severe gastrointestinal side effects, including bowel necrosis	3%	30%	56%	10%	66%	82%	89%
23	If RAASi therapy is discontinued or reduced due to the development of hyperkalemia, it should be resumed or up-titrated once normal K+ levels have been achieved	1%	8%	58%	34%	92%	–	–
Topic D: Cross-specialty alignment (cardiology & nephrology)
24	Patients with CKD and HF (cardiorenal patients) should be managed by a multidisciplinary team, including a HF specialist, a nephrology specialist, and others, who share an agreed-upon treatment plan	0%	2%	43%	56%	98%	92%	99%
25	Collaboration among medical departments will enable optimal dosing of RAASi to be maintained	0%	4%	39%	57%	96%	93%	96%
26	Recommendations for hyperkalemia management in CKD and HF guidelines should be consistent	1%	3%	36%	61%	96%	96%	95%

*Boxes with a dash in indicate no comparative statement. CKD, chronic kidney disease; CPS, calcium polystyrene sulfonate; DM, diabetes mellitus; HF, heart failure; K⁺, potassium; NSAID, nonsteroidal anti-inflammatory drug; PB, potassium binder; RAASi, renin-angiotensin-aldosterone system inhibitor; SPS, sodium polystyrene sulfonate; SZC, sodium zirconium cyclosilicate.

Agreement by Role and Years of Experience

Subanalyses examining the difference in agreement according to roles and years of experience in role were undertaken to highlight variation in responses greater than ±10% from the mean agreement, or with at least 1 subgroup not achieving the threshold of ≥75%. Supplementary Figure 2 and Supplementary Table 1 show there was a high concordance in agreement between cardiologists and nephrologists. Only statement 22 (66%) showed a difference greater than ±10% from the mean agreement, with nephrologists achieving 54% agreement and cardiologists achieving 79% agreement.

The subanalysis by years of experience, presented in Supplementary Figure 3 and Supplementary Table 2, demonstrated 6 statements with a difference greater than ±10% from the mean agreement. This analysis revealed that clinicians with 2–5 years of experience showed less agreement than their colleagues with more experience in role, with significantly lower agreement across these 6 statements.

Discussion

Risk Factors and Risk Stratification for Managing Hyperkalemia in Patients With HF and CKD

Most statements within Topic A achieved consensus, showing Japanese clinicians understand the burden associated with hyperkalemia in patients with HF and CKD. Consensus was comparable with international Delphi studies,^8,19 indicating an international agreement that hyperkalemia is a manageable side effect of RAASi medication. There was also consensus that, before reducing or discontinuing RAASi medication in response to RAASi-induced hyperkalemia, every effort should be made to control potassium levels. PBs, particularly novel binders such as sodium zirconium cyclosilicate (SZC), can potentially enable optimal RAASi dosing. The importance of managing potassium levels while maintaining RAASi therapy must be emphasized (statement S5, 100%; S6 92%). International guidelines support the use of PBs to help maintain RAASi therapy.^9,10,14 Recent Japanese research supports this, finding up-titration and maintenance of GDMT are crucial to improving patient outcomes.²⁴

Although there was consensus that RAASi should not be reduced or discontinued due to hyperkalemia, guidelines lack a cutoff value to direct clinicians on when to adhere to this approach and when to deviate. Previous consensus studies did not consider potassium ranges, and statements only refer to maintaining RAASi in mild-moderate hyperkalemia.^8,19 The current study used grouped statements to explore the serum potassium levels at which clinicians feel uncomfortable continuing RAASi treatment (5.0<K⁺≤5.5, 5.5<K⁺≤6.0, 6.0<K⁺≤6.5, and K⁺>6.5 mEq/L). There was broad agreement for maintaining RAASi therapy in mild hyperkalemia (5.0<K⁺≤5.5; S8, 88%). Only 66% agreed when considering moderate hyperkalemia (5.5<K⁺≤6.0; S9), and agreement dropped significantly for severe hyperkalemia (6.0<K⁺≤6.5; S10, 38%).

Responses clearly identified a cutoff value of 5.5 mEq/L, where clinicians begin to consider reducing or discontinuing RAASi therapy alongside intervention. For K⁺>6.5 mEq/L (S11), 74% of respondents showed disagreement, indicating the level at which RAASi medication should be adjusted, rather than solely focusing on potassium level management. This result suggested a consensus against maintaining RAASi therapy at higher potassium levels. It is possible that using wider ranges might have resulted in greater agreement, as shown in the previous comparable studies.^8,19 The narrower ranges used in this study provide better insight into when clinicians consider limiting RAASi treatment and prioritizing hyperkalemia management.

Japanese nephrology guidelines recommend that patients achieve serum potassium levels of 4.0<K⁺≤5.5 mmol/L.²⁵ A recent consensus in the Asia-Pacific region recommended that, unless a patient has acute kidney injury or significant ECG changes, serum potassium should be managed with diuretics and novel PBs.²⁶ It was also recommended that patients with serum potassium ≥6.0 mmol/L or with acute kidney injury/significant ECG changes, discontinuation of RAASi should be considered.²⁶ This is in line with the current consensus.

Agreement decreased as potassium levels increased, showing Japanese clinicians feel more comfortable maintaining RAASi doses at lower hyperkalemia levels, but believe dose reduction is important as hyperkalemia severity increases. This is potentially comparable to the statement that “Action to manage hyperkalemia should be taken when the serum K⁺ level exceeds 5.0 mmol/L” (S17, 97%) from the Chinese study.¹⁹ There is broader range of medication available to treat hyperkalemia in China, Europe and North America. Clinicians in those regions potentially have greater experience managing potassium levels therapeutically, explaining the greater level of comfort in managing moderate-severe hyperkalemia. Current results showed clinicians with 2–5 years of experience in role had the lowest agreement levels, suggesting younger clinicians may be less confident in treating patients with higher potassium levels and highlighting an educational need regarding practical hyperkalemia management in HF and CKD. However, this subgroup had less representation (n=14) than the others, so further research is warranted to explore the opinions of less experienced cardiologists and nephrologists regarding hyperkalemia management.

Prevention of Hyperkalemia for At-Risk Patients With HF and CKD

All statements in Topic B achieved consensus, with results comparable to international studies.^8,19 Only S15 (81%) achieved <90% agreement. Japanese respondents demonstrated greater support for ongoing serum potassium testing (S17, 99%) than Chinese respondents (S5, 89%), although that study did recommend testing every 3 months for patients with stage 4/5 CKD.¹⁹ Ongoing serum potassium testing is critical for patients with HF and CKD using RAASi and is needed to identify signs of hyperkalemia, ensure intervention before progression, and to help establish optimal RAASi dosing.²⁷

Topic B demonstrated high concordance between cardiologists and nephrologists, and between respondents of different experience levels. Lower agreement for S15, regarding the lack of evidence supporting a low potassium diet, was influenced by responses from those with 2–5 years of experience. This may represent another educational gap, although the efficacy of low potassium diets on serum potassium is unclear. Some studies have observed weak associations between serum potassium and dietary intake.²⁸ However, low potassium diets may deprive individuals of foods important for cardiovascular health.²⁹ The European Society for Cardiology (ESC)⁹ and Kidney Disease Improving Global Outcomes (KDIGO)³⁰ both recommend low sodium diets without potassium substitutes, to minimize hyperkalemia risk, but acknowledge the lack of high-quality data in this area.

Respondents agreed it is more important to halt the use of non-disease-modifying therapies (NDMTs) that contribute to hyperkalemia (S13, 97%). The European and North American study also supports this preventive measure (S16, 94%).⁸ NDMTs include nonsteroidal anti-inflammatory drugs (NSAIDs) and vegetable/herbal supplements. NSAIDs can compound the renin-inhibiting effect of RAASi medication and have been associated with worsening HF and CKD.^31,32 Supplements can contain high levels of potassium and may cause or exacerbate hyperkalemia, particularly in patients with impaired renal function.^14,33 Both the KDIGO¹⁰ and the UK Renal Association¹⁴ recommend review and cessation of NDMTs as a firstline approach to managing hyperkalemia. In line with this, and the recent Asia-Pacific hyperkalemia management consensus,²⁶ the SC suggests management of patients with HF and CKD should focus on the cessation of NDMTs.

Correction of Hyperkalemia for At-Risk Patients With HF and CKD Using Potassium-Lowering Therapy

All statements within Topic C, apart from S22 (66%), achieved consensus, which was comparable to other studies.^8,19 Agreement between studies shows clinicians understand the importance of maintaining RAASi therapy. The literature demonstrates that poor adherence, down-titration or discontinuation of RAASi medication in patients with HF and CKD leads to poorer prognosis.^13,34 There is agreement that novel PBs provide an option for maintaining RAASi therapy while treating hyperkalemia (S20, 96%; Burton et al. S26, 92%;⁸ Zhao et al. S19, 97%¹⁹).

S22 proved controversial, with 79% of cardiologists agreeing sodium polystyrene sulfonate (SPS) and calcium polystyrene sulfonate (CPS) should not be used in the medium–long-term, compared with 54% of nephrologists. These differences may relate to the level of experience in prescribing these medications. Comparatively, nephrologists have more familiarity with the administration of SPS/CPS. Historically, SPS and CPS were the only PBs available, and are still recommended within Japanese CKD guidelines.²⁵ The novel PB, SZC, was only approved for use in hyperkalemia management in Japan in 2020.³⁵ Discrepancies in agreement with S22 could also be due to disparities in patient populations between these clinicians. Cardiologists tend to manage patients with relatively preserved renal function who may require long-term hyperkalemia management, whereas nephrologists often see patients closer to requiring dialysis and may not anticipate long-term SPS/CPS usage and the development of associated side effects. Patiromer was not available in Japan during the survey period, so consideration of this treatment was not included within the consensus statements.

Divergences in agreement with S22 may indicate an educational gap regarding the side effects of SPS/CPS. Those with ≥20 years of experience showed 70% agreement, compared with 50% of respondents with 2–5 years, suggesting clinicians with more experience have a greater awareness of safety concerns related to SPS/CPS.^36,37 Compared with the Chinese (S23, 89%¹⁹) and European and North American studies (S32, 82%⁸), agreement from Japanese clinicians was much lower, reflecting the gap between Japanese and international guidelines regarding the use of PBs, potentially due to the more recent approval of SZC in Japan. Although SPS/CPS are still recommended in Japanese nephrology guidelines,²⁵ the management of hyperkalemia is not discussed in Japanese cardiology guidelines.³⁸ In comparison, recent guidance in China, Europe and North America states SZC should be used over SPS/CPS for long-term hyperkalemia management in HF and CKD because of its increased safety and specificity.^9,14,39–41 Research has been published recently demonstrating the benefits of novel PBs over CPS/SPS in Japanese patients,^32,42 in line with the international literature.^36,41 There is a need to highlight the importance of novel PBs and the benefits they can provide to patients with HF and CKD to help encourage a shift away from SPS/CPS.

Cross-Specialty Alignment (Cardiology & Nephrology)

Statements in Topic D achieved very strong consensus: ≥96% agreement. The current survey fielded fewer statements regarding cross-specialty alignment than other relevant Delphi studies.^8,19 However, there is definitive international alignment regarding the importance of cross-specialty patient management (S24, 98%; S33, 92%⁸; S29, 99%¹⁹). As HF and CKD are interconnected, the concept of multidisciplinary management of cardiorenal conditions is not novel.⁴³ These results help to underscore the need to develop multidisciplinary teams to ensure holistic patient care. Management of patients with HF and CKD requires long-term approaches with unified management plans.⁴⁴ Barriers still exist, given the common “silo” approach to care and disparities in resource availability.⁴³ It is important that clinicians of different specialties collaborate institutionally to manage patients, and internationally to ensure alignment across guidelines. Any joint guidance or multidisciplinary team should also seek to use the skills of allied healthcare professionals, including (but not limited to) nurse practitioners, pharmacists, nutritionists/dieticians, and primary care physicians, to fully encompass patient needs.⁴⁵

Study Strengths and Limitations

High levels of consensus were achieved from a diverse group of 250 cardiologists and nephrologists across Japan regarding the management of hyperkalemia in HF and CKD. This study used a robust survey methodology that included pattern recognition analysis. The subanalysis of agreement levels ensured that responses reflected genuine clinical perspective. The study provides valuable insights, aligning its findings with comparable studies conducted internationally.

Having fewer individuals with 2–5 years of experience limited the validity of conclusions from the subanalysis by experience. The phrasing of some statements may have caused higher levels of disagreement owing to the strong terminology. S7 received 72% agreement. Based on the trend of responses this seems unreasonably low. It may indicate an issue with the Japanese translation of the statement itself, which could have altered its intended meaning.

Proposals for Optimal Practice

A1. Optimal management of hyperkalemia in patients with HF and CKD leads to optimization of RAASi treatment, which in turn improves cardiovascular, renal, and overall prognosis.

A2. Hyperkalemia should be recognized as a predictable, treatable, and controllable side effect of RAASi therapy.

A3. In patients with HF and CKD who develop mild (5.0<K≤5.5) hyperkalemia, management of potassium levels should be prioritized by using appropriate PBs, and RAASi treatment should be continued without reduction.

A4. In patients with HF and CKD who develop moderate (5.5<K≤6.0) hyperkalemia, potassium management should be prioritized using appropriate PBs, considering the cardioprotective benefits of RAASi treatment. However, reduction or discontinuation of RAASi therapy may be considered based on the individual’s risk of hyperkalemia and the response to PBs.

A5. In patients with HF and CKD who develop severe (K>6.0) hyperkalemia, reduction or discontinuation of RAASi therapy may be considered based on the individual’s risk of hyperkalemia and the response to PBs.

B6. Novel PBs such as SZC are a viable option to manage hyperkalemia and can be used to enable and maintain optimized RAASi therapy, especially in those with a history of hyperkalemia.

B7. Patients with HF and CKD should have their potassium levels tested at least every 3 months or more according to disease severity and should cease using non-disease-modifying therapies (i.e., NSAIDs, vegetable-based supplements).

B8. Patients undergoing treatment with RAASi who have hyperkalemia, or are at risk of developing hyperkalemia, should be recommended a low potassium diet, where appropriate. In patients for whom a low potassium diet is not suitable, the use of PBs should be considered.

C9. Before discontinuing or reducing RAASi treatment due to hyperkalemia, optimal potassium management using PBs, particularly novel PBs such as SZC, should be undertaken or at least considered. PBs have the potential to enable guideline-recommended RAASi dosing, which leads to improved patient prognosis.

C10. If RAASi therapy is discontinued, or reduced, due to the development of hyperkalemia, it should be resumed, or up-titrated, once normal potassium levels have been achieved.

D11. Patients with HF and CKD should be managed by a multidisciplinary team, including cardiologists and nephrologists, who share an agreed-upon treatment plan that enables RAASi use.

D12. Recommendations for hyperkalemia management in HF and CKD guidelines should be consistent.

Conclusions

This study developed a series of actionable suggestions for the management of hyperkalemia in patients with HF and CKD in Japan. There was agreement among specialists on the importance of treating hyperkalemia as a manageable condition that can be controlled alongside optimization of RAASi therapies. Gaps regarding the management of hyperkalemia in Japan were highlighted. Future collaboration between cardiologists and nephrologists within Japan and internationally should be encouraged to help bridge these gaps and develop clear guidelines for the management of patients with HF and CKD. The suggestions presented here provide a Japanese perspective on this endeavor, and it is hoped that implementing them will promote collaborative, holistic management of patients with HF and CKD in Japan, thus improving patient outcomes.

Acknowledgments

The authors thank Dal Singh and Dr. Katie Larner from Triducive Partners Limited for conducting the literature review, facilitating group discussions, helping to identify key topics and consensus statements, liaising with M3, conducting the results analysis, and developing the manuscript.

Funding

Following studies in Europe, North America and China, this study was initiated and funded by AstraZeneca Japan. All authors received funding from AstraZeneca Japan for the study. AstraZeneca Japan commissioned Triducive Partners Limited to facilitate the project and analyze the results in line with the Delphi methodology. After engaging Triducive Partners Limited, AstraZeneca made no contribution to the study design and development, outside of honoraria payments. AstraZeneca took no part in the writing, revision or editing of the manuscript, except checking no specific medicines were promoted and that all recommendations were appropriate to drug label.

Conflicts of Interest

All authors received honoraria from AstraZeneca while undertaking this study. K. Kuwahara, K.T. and K. Kinugawa are members of Circulation Journal’s Editorial Team. Detailed COIs are available at the end of the Supplementary Information.

Authors’ Contributions

All authors developed the initial statements, contributed to the analysis and discussion of results equally, and read and approved the final manuscript.

IRB Information

PHRF-IRB (Serial Number 24F0007) confirmed that ethical approval for this study was not needed. The survey did not fall under research in the Life and Medical Guidelines. All survey respondents were informed of the research purpose and that their data would remain anonymous. Their consent was assumed through the completion and submission of their responses.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-24-0844

References

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