Where Are the Novel Tools to Treat Hyperkalemia?
When I was a resident and renal fellow in the 1970s, our armamentarium to combat hyperkalemia included intravenous calcium, calcium polystyrene sulfate, bicarbonate, insulin, and potassium-wasting diuretics. If you have failed with these interventions, the patient was put on dialysis.
Fast forward to 2015 and it seems that we are left with the same choices. To add insult to injury, today’s treatments for hypertension, systolic dysfunction, diabetics with proteinuria, chronic renal failure, and resistant hypertension include pharmaceuticals that not only prolong life, but also cause or aggravate hyperkalemia. These include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and spironolactone. Talk about being between a rock and a hard place.
Now, all of sudden, our archaic therapeutics may change drastically.
Two Top Papers1,2 have identified a medication that is both safe and effective in potassium removal. Patiromer is a high capacity, oral, nonabsorbed polymer that binds potassium in exchange for calcium in the colon.
The first study1 started patients with chronic kidney disease and hyperkalemia (5.1-6.5 meq/L) who were taking renin-angiotensin-aldosterone system (RAAS) inhibitors on patiromer for 4 weeks in the initial treatment phase. After 4 weeks, 76% of the patients reached their target “lower” potassium value.
Eligible patients at the end of week 4 (potassium level of 5.5-<6.5 mmol/L, which decreased to 3.8-<5.1 mmol/L) entered an 8-week withdrawal phase, where they were randomly assigned to continue patiromer or switch to placebo. The data showed that hyperkalemia recurred in 60% of the placebo group versus only 15% in the patiromer folks at 8 weeks. Note: Side effects included constipation and low magnesium, but keep in mind that the pharmaceutical is aimed at replacing calcium polystyrene resin, which has perforated and caused bowel necrosis.
In the second study,2 patients with diabetes who had serum potassium levels >5.0 meq/L and were receiving RAAS inhibitors were subjects. Based on increasing levels of serum potassium, incrementing doses of patiromer were given. From weeks 4 through 52, significantly decreased levels of potassium were achieved, again with few serious side effects. Hypokalemia occurred in 5.6% of those treated.
Patiromer is not yet FDA approved, however, it seems that its efficacy and safety will lead to approval—possibly later this year. Will primary care find it useful? Just think about how many times you have needed to treat a diabetic with an ACE or ARB, but had your hands tied by a potassium level that is >5 meq/L. What about those patients you follow with severe systolic dysfunction that also cannot take an ACE or an ARB and have recurrent episodes of heart failure? You had to decrease or discontinue the use of calcium polystyrene sulfate because some of the side effects were fatal or at least severely debilitating (eg, perforated bowel requiring surgery).
My training era in the 1970s is long gone. So should the “old” manner of treating of elevated potassium. We are on to something good here!
Gregory W. Rutecki, MD, is a physician at the National Consult Service at the Cleveland Clinic. He is also a member of the editorial board of Consultant. Dr Rutecki reports that he has no relevant financial relationships to disclose.
1.Weir MR, Bakris GL, Bushinsky DA, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015;372(2):211-221.
2.Bakris GL, Pit B, Weir MR, et al. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease. The AMETHYST-DN randomized clinical trial. JAMA. 2015;314(2):151-161.