Burden and Treatment of Hyperkalemia

Hyperkalemia (HK), defined as serum potassium (sK+) >5.0 mmol/L, is a common and potentially serious condition among patients with chronic kidney disease (CKD).

Guidelines recommend the use of renin-angiotensin-aldosterone system inhibitors (RAASi) to delay or prevent CKD progression, and these are sometimes augmented with sodium-glucose cotransporter 2 inhibitors (SGLT2i) or nonsteroidal mineralocorticoid receptor antagonists (MRA) to improve kidney and cardiovascular outcomes. The use of RAASi and MRA can lead to HK, which is sometimes addressed by down-titrating or discontinuing RAASi. However, the latest guidelines and Delphi consensus recommendations discourage changes to RAASi therapy in favor of trying to reduce sK+ levels. One way of doing this is through the use of novel potassium (K+) binders, such as sodium zirconium cyclosilicate or patiromer.

Steven Fishbane, MD, and other researchers posited that a better understanding of the burden and real-world treatment of HK in CKD patients can inform HK management approaches. Therefore, they conducted an analysis utilizing data from the observational DISCOVER CKD study to describe HK burden in CKD patients; treatment pathways for key medications prescribed within 3 months of HK index, including RAASi, diuretics, and K+ binders; and characteristics of patients initiating K+ binders during the observation period. Their findings were published in Kidney360.

Retrospective data from DISCOVER CKD came from the UK Clinical Practice Research Datalink (2008-2019) and Japan Medical Data Vision (2008-2017) databases. Fishbane et al compared patients with CKD (two estimated glomerular filtration rate [eGFR] measures <75 mL/min/1.73 m² recorded ≥90 days apart) and HK (at least two serum potassium [sK+] measures >5.0 mmol/L) with patients without HK (sK+ <5.0 mmol/L). The HK index event was the second sK+ measurement.

There were 37,713 patients with HK and 142,703 patients without HK from the UK Clinical Practice Research Datalink included in the analysis (HK prevalence, 20.9%). There were 5924 patients with HK and 74,272 patients without HK from Japan Medical Data Vision included in the analysis (HK prevalence, 7.4%). Across both databases, patients with HK had lower median estimated eGFR and more prevalent comorbidities, such as hypertension, heart failure, type 2 diabetes, and acute kidney injury versus patients without HK. Most patients were receiving RAASi at the time of HK index.

Study outcomes included baseline characteristics and treatment pathways for key medications (RAASi, diuretics, and K+ binders). The analysis found that treatment pathways were more heterogeneous in Japan. In Japan, 18.7% of patients started receiving K+ binders within 3 months of HK index. In the United Kingdom, <0.2% of patients did. In Japan, 22.9%, 53.6%, and 29.2% of patients discontinued treatment with diuretics, K+ binders, and RAASi, respectively. In the United Kingdom, those proportions were 48.7%, 76.5%, and 50.6%.

The authors acknowledged limitations of the study, most notably the use of real-world data, leading to some gaps in data. Data regarding occurrence of metabolic acidosis and prescription of sodium bicarbonate to manage metabolic acidosis, both of which can affect the extent of HK, were not reported consistently across databases. Analysis of individual medications was not possible. The rationale for medications’ use or nonuse could not be determined, nor was the reinitiation of treatment evaluated. Outcomes of interest may have been underreported or misclassified. Finally, differences between the data sources could impact interpretation and treatment approaches.

In sum, HK was associated with increased comorbidity burden in patients with CKD. Treatment of HK varied between the United Kingdom and Japan. HK treatment pathways are more heterogeneous in Japan, and potassium binders are more commonly prescribed there compared with the United Kingdom.

The authors wrote, “This finding is consistent with the observations reported elsewhere and likely reflects a previous lack of consensus on how to manage episodes of HK in patients with CKD. The latest guidelines and Delphi consensus recommendations reinforce the benefits of maintaining RAASi treatment in these patients and propose several measures to reduce sK+. Studies are now warranted to determine whether these measures can facilitate the continuation of RAASi treatment and to determine the effect of a second HK episode.”

Source: Kidney360