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Managing Hyperkalemia in High-Risk Patients in Long-Term Care
Rajeev Kumar, MD, FACP; Leo Kanev, MD; Steven D. Woods, PharmD; Melanie Brenner, PharmD; and Bernie Smith, RPh, MBA, MHA

Managing Hyperkalemia in High-Risk Patients in Long-Term Care

Rajeev Kumar, MD, FACP; Leo Kanev, MD; Steven D. Woods, PharmD; Melanie Brenner, PharmD; and Bernie Smith, RPh, MBA, MHA

Hyperkalemia is common among elderly patients and is associated with an increase in morbidity and mortality. Patients at highest risk for developing hyperkalemia are those with chronic kidney disease (CKD) and heart failure (HF), particularly those on guideline-recommended inhibitors of the renin-angiotensin-aldosterone system (RAAS). Hyperkalemia remains a challenge for clinicians practicing in the long-term care setting as they are often faced with the difficult decision of down-titrating or discontinuing RAAS inhibitors in response to hyperkalemia in the very patients who derive the greatest benefit from these agents. In the past, options to chronically manage hyperkalemia were limited. Patiromer was approved for the treatment of hyperkalemia in 2015 and has been shown to maintain normokalemia for up to 52 weeks in patients with CKD and/or HF on RAAS inhibitors. With the emergence of a new hyperkalemia treatment, there could be a paradigm shift away from the discontinuation of guideline recommended therapies, allowing the continuation of RAAS inhibitor therapy to effectively manage HF symptoms and reduce the risk of rehospitalization in patients with HF, and slow the progression to end-stage renal disease in patients with CKD.
Am J Manag Care. 2017;23:-S0

Hyperkalemia is clinically one of the most important electrolyte abnormalities that can lead to cardiac arrhythmias and sudden cardiac death. Elderly patients, because of many underlying conditions, are particularly predisposed to develop this electrolyte disturbance.1 A combination of age-associated reductions in glomerular filtration rate (GFR) and disturbances in the renin-angiotensin-aldosterone system (RAAS) and renal tubular function lead to this predisposition.1,2 The prevalence of hyperkalemia in the general population has been estimated at 2% to 3%.3 However, studies in older patients with chronic kidney disease (CKD) show much higher frequencies of hyperkalemia—as high as 50%—particularly in those with advanced stages of CKD, diabetes, and heart failure (HF) and in patients treated with RAAS inhibitors (RAASIs).3-5

Background and Significance
The number of elderly people (aged ≥65 years) in the world is estimated to increase more than two-fold from 420 million (6.9% of the world population) in the year 2000 to 973 million (12.0%) in 2030.6 In the United States, the number of elderly people doubled from 1960 to 2000, and it is estimated to double again to 71 million by 2030.6,7

The projected medical and economic burden of the aging population on the healthcare system is significant.8 The aging population requires a focus on chronic diseases, such as heart disease, cancer, respiratory disease, cerebrovascular disease, dementia, diabetes, and kidney disease.9 Chronic diseases are often associated with disability, which leads to an increased use of long-term care services, such as nursing homes, assisted living facilities, and home healthcare.10 Over two-thirds of individuals who reach 65 years of age are projected to need long-term care in their lifetime—for an average of 3 years.11,12 Nursing home residents, because of their chronic conditions, take an average of 6.7 different medications per day.13 Chronic diseases are a significant medical burden, potentially leading to hospitalizations, invasive medical procedures (eg, dialysis), poor quality of life, and increased mortality in the community and in long-term care settings.10

This article reviews the current understanding of how elderly patients with CKD and/or HF may develop hyperkalemia, and how the recent advent of new treatment strategies may be helpful in improving clinical outcomes in these patients.

The prevalence of CKD and end-stage renal disease (ESRD) in the United States, especially in older individuals, is high and growing.14 The 2015 United States Renal Data System annual data report revealed the prevalence of CKD and ESRD in the Medicare population to be approximately 11%.15 Interestingly, although the incidence of ESRD has generally plateaued in the last decade, its prevalence has continued to rise by approximately 21,000 cases per year.15 Consistent with this, the prevalence of patients receiving dialysis (hemodialysis and peritoneal dialysis) increased by 4%, and of those receiving a renal transplant, it increased by 3.1%.15 This increase in prevalence has generally been attributed to increased longevity.15

The decision of whether or not to start dialysis in patients with advanced CKD can be difficult, especially in elderly patients with multiple comorbidities.16-18 Advanced age, poor functional assessment, disabilities, and conditions such as dementia and depression should be taken into consideration. In a recent retrospective national cohort analysis of more than 28,000 patients with a sustained estimated GFR (eGFR) less than 15 mL/min/1.73 m2, it was found that the proportion of patients who received, or were preparing to receive, renal replacement therapy differed significantly between younger and older populations: 96% for patients aged less than 45 years and 53% for those 85 years and older.19 Consistent with this finding, the patients deciding against dialysis were significantly older (mean age, 75 years) and had a significantly higher Gagne comorbidity score (mean, 6.1), including greater rates of dementia and stroke.19

Reducing overactivity of the RAAS with RAASIs has shown significant renoprotective benefit in patients with CKD in multiple clinical trials, including RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) and IDNT (Irbesartan Diabetic Nephropathy Trial).20-24 Although no RAASI clinical trial has assessed mortality as the primary end point in patients with CKD, a large observational study showed an association between RAASI use and lower mortality in patients with CKD.25 For these reasons, use of RAASIs is recommended by guidelines.26,27 The National Kidney Foundation’s Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines recommend using angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) at moderate-to-high doses in patients with diabetic or nondiabetic kidney disease with proteinuria, with or without hypertension.28 More recent hypertension guidelines (Eighth Joint National Committee) also support the use of RAASIs in adult patients with CKD and hypertension.27 The major incentive for using RAASIs in patients in the long-term care setting goes beyond blood pressure control and includes a reduction in intraglomerular pressure and proteinuria, thereby slowing the progression of CKD to ESRD. However, because these patients are typically elderly, have renal insufficiency, and are taking multiple medications, providers may be concerned about the risk versus benefit of prescribing RAASIs in these patients for fear of increased serum creatinine, reduced GFR, or hyperkalemia.

RAAS inhibition with an ACEI or ARB can result in an acute increase in serum creatinine and/or fall in eGFR in patients with CKD.29 The rise in serum creatinine may lead physicians to discontinue or reduce the dose of these disease-delaying medications.29 Many physicians view this rise in serum creatinine as a contraindication for future RAASI use. Clinical trial data demonstrate that serum creatinine rises transiently and stabilizes relatively quickly in patients with diabetic or nondiabetic kidney disease.29 It is now generally accepted that an elevation in serum creatinine of up to 30% to 35% that stabilizes within the first 2 months of RAASI therapy is associated with good prognosis and long-term preservation of kidney function.29,30

Another major concern related to usage of RAASIs is hyperkalemia. Patients with CKD on RAASI therapy, especially the elderly, commonly develop this electrolyte abnormality.2,31-33 RAASI-induced hyperkalemia has been associated with an increased risk of adverse renal outcomes in patients with diabetic nephropathy.34 Hyperkalemia has also been associated with an increased risk of sudden death in patients undergoing chronic dialysis.35 In large retrospective analyses, hyperkalemia in patients with CKD and/or on dialysis was correlated with an increased risk of death.4,36-38 Therefore, it is recommended that serum potassium (K+) level be closely monitored, as follows in patients with CKD who are on RAASI therapy: every 2 to 4 weeks if baseline serum K+ level (at initiation or dose increase of RAASI) is 4.6 to 5.0 mEq/L, and every 2 weeks or less if the baseline serum K+ level is greater than 5.0 mEq/L.28,39 The K/DOQI guidelines recommend reducing the dose of an ACEI or ARB by 50% if hyperkalemia (serum K+ level >5.0 mEq/L) develops and re-evaluating serum K+ level every 5 to 7 days.28 If serum K+ level does not return to baseline in 2 to 4 weeks, RAASI therapy should be discontinued.28 It should be noted, however, that these guidelines were developed before the recent advent of new and more tolerable therapies for the treatment of hyperkalemia.

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