Chronic kidney disease (CKD), heart failure and diabetes mellitus encompass the leading risk factors in the development of chronic hyperkalaemia which puts patients at increased risk of mortality and morbidity . The occurrence of hyperkalaemia often precludes patients benefiting from maximal doses of RAAS inhibition and is itself linked to worsening clinical outcomes . NICE have approved the use of sodium zirconium cyclosilicate and patiromer in both the acute and, more recently, the chronic management of hyperkalaemia. The use of these agents for the chronic management of hyperkalaemia could prove pivotal in the treatment for such patient groups. The indication is additional to the use of sodium zirconium cyclosilicate and patiromer in the management of acute hyperkalaemia.
Outpatient studies evaluating the use of these newer potassium binding agents within selected chronic kidney disease patient groups experiencing hyperkalaemia has demonstrated the correction and maintenance of normokalaemia  as well as the ability to maintain or increase the dose of RAAS inhibition in a significant proportion of patients . These findings were predominantly in those patients with moderate to severe CKD, where 75% were CKD stage 3 or 4, and this mirrors the patient group reported on within this general nephrology clinic.
Current therapeutic options available for managing chronic hyperkalaemia are suboptimal  and the introduction of new potassium binding agents provides a new clinical opportunity. In order to implement the effective use of new potassium binders, Imperial College Healthcare NHS Trust have developed a new cross departmental guideline to ensure the optimal use of these agents to maximise the inhibition of RAAS in the patient groups who are likely to benefit from this. This audit collected data from unselected patients within a single general nephrology clinic in one trust, fundamentally finding that 14% of patients could benefit from chronic use of sodium zirconium cyclosilicate or patiromer to better manage their underlying chronic kidney disease, diabetes mellitus and heart failure.
When considering diabetes, hyperkalaemia is probably contributed to by the syndrome of hyporeninaemic hypoaldosteronism, resulting from mild-to-moderate renal impairment . Such patients typically present with asymptomatic hyperkalaemia, commonly occurring in elderly diabetics particularly those on SGLT-2 inhibitor and RAAS inhibitor therapy in the context of impaired renal function . It is important to always consider concomitant medication in case these may be aggravating the hyperkalaemia.
This audit is limited to hospital outpatients and fails to consider the impact on the large number of patients within primary care and in the community with chronic kidney disease, diabetes mellitus and heart failure. General practitioners face many barriers in managing heart failure patients in the community who tend to be frail, elderly with polypharmacy and multiple co-morbidities adding to their risk for hyperkalaemia. The lack of awareness of the diagnosis of heart failure is likely to act as a further barrier to effective treatment . But with growing numbers of heart failure patients seen in community cardiology clinics by general practitioners with a special interest, there is better scope for the potential use of these therapeutic agents to maximise the beneficial effects of RAAS inhibition .
Many patients with CKD receive suboptimal treatment due to difficulties with regular monitoring or even because they are undiagnosed, given that CKD remains largely asymptomatic. Without regularly screening diminishing renal function may go undetected, leaving a significant percentage of the population with CKD undiagnosed . This illustrates the potential wider reaching impact which these newer potassium binding agents can have in the management of these chronic conditions in primary care and within the community.
Within this study patients who experienced hyperkalaemia associated with an episode of acute kidney injury (AKI), defined earlier in the methodology, were excluded as being not suitable for sodium zirconium cyclosilicate or patiromer. It is however not clear whether these episodes of acute kidney injury occurred in response to medications such as RAAS inhibitors or due to other reversible causes such as sepsis and hypovolaemia . Potentially re-challenging such patients in controlled environments with monitoring of their renal profiles to assess for a recurring AKI could help determine their suitability for these newer potassium binding agents going forward.
Of the patient group with hyperkalaemia limiting maximisation of RAAS inhibition, 73% were on regular oral sodium bicarbonate treatment to help manage their metabolic acidosis and reduce serum potassium levels. This has been proven to have a beneficial effect on hyperkalaemia in both short and long-term studies . However, there was insufficient effect of this manoeuvre in the reported patients to enable an initiation or up-titration in RAAS inhibitor therapy. Studies report beneficial outcomes with sodium bicarbonate therapy in CKD patients who are at increased risk of hyperkalaemia including those on RAAS inhibition . Further to this, sodium zirconium cyclosilicate has been shown to increase sodium bicarbonate levels  which could further assist in the correction of the metabolic acidosis within CKD.
A limitation of the data is whether the patients identified in this clinic would tolerate the new potassium binders. Patiromer can cause abdominal pain and gastrointestinal side effects, whilst sodium zirconium cyclosilicate can result in fluid retention and oedema [13, 14]. An ideal study would be to demonstrate whether the introduction of these agents to patients who are identified as needing the drug within clinics are successfully treated, to better understand its impact.