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As a nephrologist, I often monitor my patients living with chronic kidney disease (CKD) for hyperkalemia (HK), a related and often-recurrent condition characterized by higher-than-normal serum potassium levels (>5.0 mEq/L).1-3 HK can vary in severity from mild to life-threatening, and symptoms may include weakness, fatigue, nausea, vomiting, or heart palpitations.4 In addition to CKD, HK can also be associated with heart failure (HF), and the interconnectedness of these diseases can lead to worsening symptoms and a higher risk of all-cause mortality associated with HK.5-7
In patients with HF, renin-angiotensin-aldosterone system inhibitor (RASSi) therapy is recommended to improve clinical outcomes.8 Side-effects of RAASi therapy can include elevated potassium levels leading to HK.9 It’s important for healthcare professionals who treat HF, particularly cardiologists, to be well educated on HK and the importance of timely and long-term treatment so they can effectively manage their patients’ health.10
The Danger of Down-Titrating RAASi Therapy to Treat HK
Reducing or discontinuing RAASi therapy has been a common approach to managing HK.11 A retrospective analysis from the Humedica health records database analyzed medical data for 66,862 patients with HK over a 12-month period. Of those with at least one outpatient RAASi prescription (excluding patients with end-stage renal disease, stage 5 CKD, and acute kidney injury), approximately 50% who experienced a moderate-to-severe HK event, defined as serum potassium levels ≥5.5 mEq/L, had their RAASi therapy stopped or reduced.11 Some may not know that is this discontinuation strategy can lead to worsen patient outcomes.12
A retrospective study of electronic health records at Kaiser Permanente evaluated the mortality risks associated with continuation/discontinuation of RAASi therapy among 5728 adults with new-onset HK (first serum potassium ≥5.0 mEq/L) and CKD (eGFR <60 mL/min/1.73 m2;excluding eGFR <15 mL/min/1.73 m2 patients on dialysis, history of kidney transplant or HF) between 2016-2017.12 Patients had at least two fills of RAASi medication within 12 months before new-onset HK.12 RAASi discontinuation was defined as ≥ 90-day gap in refills within 3 months after new-onset HK.12 Patients who discontinued RAASi (n=776) during the follow-up period (median follow-up of 2 years) had a 34% increased risk of all-cause mortality (adjusted HR 1.34; 95% confidence interval 1.14-1.56) compared to patients who continued RAASi therapy (n=4952).12
Instead of down-titrating or discontinuing RAASi to address HK, physicians can add a potassium binder (K+ binder). Treating HK could help enable guideline-recommended RAASi treatment.8,13-14 Treatment guidelines recommend use of K+ binders to treat HK, and the International Society of Nephrology (ISN) came to a similar consensus after convening nephrologists and cardiologists from the American Society for Preventative Cardiology (ASPC), the Heart Failure Association of the European Society of Cardiology (HFA), Kidney Disease Improving Global Outcomes (KDIGO) and the Renal Physicians Association (RPA) to co-create a toolkit for the optimization of RAASi therapy in 2021.8,13-15
Dietary changes alone are often insufficient to manage HK effectively.16 REVOLUTIONIZE I, a retrospective, real-world evidence study of US electronic health records, evaluated the recurrence of HK following dietary counseling in adults with HK and stage 3/4 CKD.17 Six months following dietary counseling, the percentage of patients with Stage 3/4 CKD who had recurrent HK, defined as serum K+ >5.0 mEq/L that was at least seven days apart from a prior lab evidence of HK, increased from 37.4% (n=1790) at one month to 56% (n=842) at six months.17
In my practice, we adhere to guideline recommendations and treat patients living with recurrent HK using K+ binders like LOKELMA® (sodium zirconium cyclosilicate) 5 g and 10 g for oral suspension. LOKELMA is a modern potassium binder indicated for the treatment of hyperkalemia in adults.18 LOKELMA should not be used as an emergency treatment for life-threatening HK because of its delayed onset of action.
In clinical trials, LOKELMA demonstrated a rapid reduction of potassium as early as 1 hour and sustained normal levels of potassium (normokalemia) for up to 1 year with continued treatment in adult patients with HK who were not on dialysis.18-21
The Importance of Timely and Long-Term HK Treatment
As healthcare providers, we recognize that compromising RAASi therapy risks adverse outcomes. Long-term treatment for HK is equally crucial, so opting for therapeutic options like LOKELMA to reduce potassium levels can help.
Both nephrologists and cardiologists have a responsibility to educate themselves on the latest guideline recommendations and make informed treatment decisions on behalf of patients and their families. For the management of HK, I confidently administer LOKELMA, since it was proven to be safe and generally well tolerated. To learn more about LOKELMA, visit www.lokelma-hcp.com.
IMPORTANT SAFETY INFORMATION for LOKELMA® (sodium zirconium cyclosilicate)
Warnings and Precautions:
Gastrointestinal Adverse Events in Patients with Motility Disorders: Avoid LOKELMA in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders. LOKELMA has not been studied in patients with these conditions and it may be ineffective and may worsen gastrointestinal conditions.
Edema: Each 5-g dose of LOKELMA contains approximately 400 mg of sodium, but the extent of absorption by the patient is unknown. In clinical trials of LOKELMA in patients who were not on dialysis, edema was observed and was generally mild to moderate in severity and was more commonly seen in patients treated with 15 g once daily. Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (eg, heart failure or renal disease). Advise patients to adjust dietary sodium, if appropriate. Increase the dose of diuretics as needed.
In a clinical trial of LOKELMA in patients on chronic hemodialysis in which most patients were treated with doses of 5 g to 10 g once daily on non-dialysis days, there was no difference in the mean change from baseline in interdialytic weight gain (a measure of fluid retention) between the LOKELMA and placebo groups.
Hypokalemia in Patients on Hemodialysis: Patients on hemodialysis may be prone to acute illness that can increase the risk of hypokalemia on LOKELMA (eg, illnesses associated with decreased oral intake, diarrhea). Consider adjusting LOKELMA dose based on potassium levels in these settings.
Diagnostic Tests: LOKELMA® (sodium zirconium cyclosilicate) has radio-opaque properties and, therefore, may give the appearance typical of an imaging agent during abdominal X-ray procedures.es.
ADVERSE REACTIONS: The most common adverse reaction in non-dialysis patients with LOKELMA was mild to moderate edema. In placebo-controlled trials up to 28 days, edema was reported in 4.4%, 5.9%, 16.1% of non-dialysis patients treated with 5 g, 10 g, and 15 g of LOKELMA® once daily, respectively vs 2.4% of non-dialysis patients receiving placebo.
DRUG INTERACTIONS: LOKELMA can transiently increase gastric pH. In general, oral medications with pH-dependent solubility should be administered at least 2 hours before or 2 hours after LOKELMA. Spacing is not needed if it has been determined the concomitant medication does not exhibit pH-dependent solubility.
INDICATION AND LIMITATION OF USE
LOKELMA is indicated for the treatment of hyperkalemia in adults.
LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
Please read full PRESCRIBING INFORMATION.