Hyperkalaemia

Hyperkalaemia

How common is hyperkalaemia?

The prevalence of hyperkalaemia in the general population has not been well documented but is thought to be low, estimated at 2–3%^1,2. Prevalence is considerably higher in people with chronic diseases, including heart failure and chronic kidney disease (CKD), and in hospitalised patients^2,3. People with CKD are particularly susceptible to imbalances in potassium levels, given that the kidneys play a major role in maintaining potassium homeostasis^4,5. Despite the greater risk of hyperkalaemia in patients with CKD, however, there is variation in prevalence estimates, with reports of 2–34.5%, depending on the stage of CKD^2,6. Hyperkalaemia is associated with increased morbidity and mortality in patients with CKD, particularly those with comorbid heart failure and diabetes⁵.

What are risk factors for hyperkalaemia?

The main risk factor for hyperkalaemia is renal impairment and there is a strong correlation between high potassium levels and declining estimated glomerular filtration rate (eGFR)^2,7,8. Coronary heart disease and diabetes mellitus are also well-known risk factors for hyperkalaemia, as are several classes of drugs, including renin-angiotensin-aldosterone system (RAAS) inhibitors and potassium-sparing diuretics⁷. The depolarising effect of hyperkalaemia has potentially life-threatening consequences, including increased risk of cardiac arrythmias and metabolic acidosis⁵.

What are unmet needs in hyperkalaemia?

Although hyperkalaemia is a common and potentially fatal complication of CKD and other chronic diseases, several unmet needs are yet to be addressed. At present, there is poor consensus regarding the definition of hyperkalaemia and no uniform guidelines for optimal management^5,9. Consequently, there is wide variation in monitoring and treatment approaches, including drug choice and dosage^5,9. Treatment strategies include discontinuing or reducing the dose of RAAS inhibitors and restricting dietary intake of potassium. These strategies deprive patients of beneficial therapies and nutrient-rich foods^5,8. In addition, direct evidence to support the efficacy of restricting dietary intake of potassium is lacking⁸. There are several pharmacological options available for the treatment of hyperkalaemia, but limited data to support efficacy and, often, a poor safety profile⁹.

What are the targeted treatments for hyperkalaemia?

The development of potassium-binders offers an alternative approach to dietary restriction of potassium or discontinuation of RAAS therapy in the treatment of hyperkalaemia^5,10. These agents are administered orally and reduce serum levels of potassium through ion-exchange mechanisms in the gastrointestinal tract. Two potassium binders, patiromer and sodium zirconium cyclosilicate, have been evaluated in clinical trials and were found to be effective in reducing serum potassium levels in patients with CKD without the need to discontinue RAAS therapy. Patiromer and sodium zirconium cyclosilicate were also generally well tolerated. Recently, both agents were approved in the US and Europe for treatment of hyperkalaemia⁵.

References

1. Portolés J, Martín L, Broseta JJ, Cases A. Anemia in Chronic Kidney Disease: From Pathophysiology and Current Treatments, to Future Agents. Front Med. 2021;8:328.
2. Bianchi S, Aucella F, De Nicola L, Genovesi S, Paoletti E, Regolisti G. Management of hyperkalemia in patients with kidney disease: a position paper endorsed by the Italian Society of Nephrology. J Nephrol. 2019;32(4):499.
3. Kovesdy CP. Epidemiology of hyperkalemia: an update. Kidney Int Suppl. 2016;6(1):3.
4. Seliger SL. Hyperkalemia in patients with chronic renal failure. Nephrol Dial Transpl. 2019;34(Suppl 3):iii12–iii18.
5. Palmer BF, Carrero JJ, Clegg DJ, Colbert GB, Emmett M, Fishbane S, et al. Clinical Management of Hyperkalemia. Mayo Clin Proc. 2021;96(3):744–762.
6. Watanabe R. Hyperkalemia in chronic kidney disease. Rev Assoc Med Bras. 2020;66(1):31–36.
7. Hunter RW, Bailey MA. Hyperkalemia: pathophysiology, risk factors and consequences. Nephrol Dial Transplant. 2019;34(Suppl 3):III2–III11.
8. Clase CM, Carrero JJ, Ellison DH, Grams ME, Hemmelgarn BR, Jardine MJ, et al. Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2020;97(1):42–61.
9. Rafique Z, Chouihed T, Mebazaa A, Peacock WF. Current treatment and unmet needs of hyperkalaemia in the emergency department. Eur Heart J. 2019;21(Suppl A):A12–A19.
10. Morales E, Cravedi P, Manrique J. Management of Chronic Hyperkalemia in Patients With Chronic Kidney Disease: An Old Problem With News Options. Front Med. 2021;8:768.