Prediction and Management of Hyperkalemia Across the Spectrum of Chronic Kidney Disease
Department of Medicine, ASH Comprehensive Hypertension Center, The University of Chicago Medicine, Chicago, IL 60637 Seminars in Nephrology
(Impact Factor: 3.48).
05/2014; 34(3). DOI: 10.1016/j.semnephrol.2014.04.008
Hyperkalemia commonly limits optimizing treatment to slow Stage 3 or higher CKD progression. The risk of hyperkalemia is linked to dietary potassium intake, level of kidney function, concomitant diseases that may affect potassium balance such as diabetes and use of medications that influence potassium excretion. The risk predictor for developing hyperkalemia are an estimated glomerular filtration rate of <45 ml/min/1.73m2 and a serum potassium level >4.5 mEq/L in the absence of blockers of the renin angiotensin aldosterone system (RAAS). Generally, monotherapy with RAAS blockers does not increase risk substantially unless hypotension or volume depletion occur. Dual RAAS blockade involving any combination of an ACEI, ARB, renin inhibition or aldosterone receptor blocker markedly increases risk of hyperkalemia in those with Stage 3 or higher CKD. Moreover, dual RAAS blockade further reduces albuminuria by 25-30% over monotherapy, it has failed to demonstrate a benefit on CKD progression or cardiovascular outcome, thus, not indicated in such patients due its marked increase in hyperkalemia potential. While sodium polystyrene resins exist to manage hyperkalemia in those requiring therapy that increase serum potassium, they are not well tolerated. Newer more predictable, better tolerated polymers to bind potassium are on the horizon and may be approved within the next one to two years.
Available from: nejm.org
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Hyperkalemia increases the risk of death and limits the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) in high-risk patients. We assessed the safety and efficacy of patiromer, a nonabsorbed potassium binder, in a multicenter, prospective trial.
Patients with chronic kidney disease who were receiving RAAS inhibitors and who had serum potassium levels of 5.1 to less than 6.5 mmol per liter received patiromer (at an initial dose of 4.2 g or 8.4 g twice a day) for 4 weeks (initial treatment phase); the primary efficacy end point was the mean change in the serum potassium level from baseline to week 4. Eligible patients at the end of week 4 (those with a baseline potassium level of 5.5 to <6.5 mmol per liter in whom the level decreased to 3.8 to <5.1 mmol per liter) entered an 8-week randomized withdrawal phase in which they were randomly assigned to continue patiromer or switch to placebo; the primary efficacy end point was the between-group difference in the median change in the serum potassium level over the first 4 weeks of that phase.
In the initial treatment phase, among 237 patients receiving patiromer who had at least one potassium measurement at a scheduled visit after day 3, the mean (±SE) change in the serum potassium level was -1.01±0.03 mmol per liter (P<0.001). At week 4, 76% (95% confidence interval, 70 to 81) of the patients had reached the target potassium level (3.8 to <5.1 mmol per liter). Subsequently, 107 patients were randomly assigned to patiromer (55 patients) or placebo (52 patients) for the randomized withdrawal phase. The median increase in the potassium level from baseline of that phase was greater with placebo than with patiromer (P<0.001); a recurrence of hyperkalemia (potassium level, ≥5.5 mmol per liter) occurred in 60% of the patients in the placebo group as compared with 15% in the patiromer group through week 8 (P<0.001). Mild-to-moderate constipation was the most common adverse event (in 11% of the patients); hypokalemia occurred in 3%.
In patients with chronic kidney disease who were receiving RAAS inhibitors and who had hyperkalemia, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia. (Funded by Relypsa; OPAL-HK ClinicalTrials.gov number, NCT01810939.).
New England Journal of Medicine 11/2014; 372(3). DOI:10.1056/NEJMoa1410853 · 55.87 Impact Factor
American Journal of Pharmacy Benefits 03/2015; 7(2):81-83.
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ABSTRACT: Apparent treatment-resistant hypertension (aTRH) is defined as blood pressure (BP) >140/90 mmHg despite three different antihypertensive drugs including a diuretic. aTRH is associated with an increased risk of cardiovascular events, including stroke, chronic renal failure, myocardial infarction, congestive heart failure, aortic aneurysm, atrial fibrillation, and sudden death. Preliminary studies of renal nerve ablation as a therapy to control aTRH were encouraging. However, these results were not confirmed by the Symplicity 3 trial. Therefore, attention has refocused on drug therapy. Secondary forms of hypertension and associated conditions such as obesity, sleep apnea, and primary aldosteronism are common in patients with aTRH. The pivotal role of aldosterone in the pathogenesis of aTRH in many cases is well recognized. For patients with aTRH, the Joint National Committee-8, the European Society of Hypertension, and a recent consensus conference recommend that a diuretic, ACE inhibitor, or angiotensin receptor blocker and calcium channel blocker combination be used to maximally tolerated doses before starting a 'fourth-line' drug such as a mineralocorticoid receptor (MR) antagonist. Although the best fourth-line drug for aTRH has not been extensively investigated, a number of studies summarized here show that an MR antagonist is effective in reducing BP when added to the standard multi-drug regimen.
Drugs 03/2015; 75(5). DOI:10.1007/s40265-015-0372-3 · 4.34 Impact Factor
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