PEARL-HF: RLY5016--A cure for hyperkalemia phobia and a help for needy CHF patients?

I'll never forget my horrifying first experience with hyperkalemia. While rounding at Jewish Hospital in Louisville, KY as a senior medical student, a code was called on "8 towers." I ran up the stairs and through the door to the usual code frenzy with CPR in progress, both sides of the bed flanked with nurses and techs performing their lifesaving break-dance with syringes and paddles. Their subject was a large African American male whose girth made it nearly impossible for adequate chest compressions. Intubation was quickly accomplished by the ER physician, who was yelling orders as he worked. A rhythm strip was run, torn off the printer and handed to me for interpretation. (Why me? I asked myself, as I stood speechless at what I saw). Luckily for the victim, my attending arrived just seconds behind me, grabbed the ECG strip from my hands and immediately ordered an amp of calcium gluconate. I'll never forget the triangular-shaped QRS complex, frighteningly wide and sprawled across "two big boxes," appearing more like a child's drawing than anything resembling an electrical cardiac cycle. Amazingly, despite a potassium level of greater than 8.0, this burly gentleman with "way too much of a good thing" survived. He was a chronic dialysis patient who, after much interrogation, admitted to his habit of paying a neighborhood child to run to the grocery and purchase sacks full of "limes to suck on" to alleviate his thirst. He reasoned that since lemons were so high in potassium, he might utilize limes as an adequate substitute. He was a "frequent flier" at the hospital, and this time, his penchant for citrus almost caused him to "fly away."

Lessons like this are not soon forgotten, so when the presenter of the PEARL-HF study rightly pointed out that the "fear" of hyperkalemia often prevents therapy with ARBs and ACE inhibitors, he was correct. The fear is justified and a real impediment to optimal heart-failure management in many. Since it was stated today that the risk of death increases by 10-fold on the day following a potassium level of >=5.5, abnormal potassium levels demand the respect they are owed. Kayexalate, a poorly tolerated solution for hyperkalemia with side effects of bowel necrosis and what I fondly refer to as "third-degree-burn diarrhea," has been our only real ally in the fight to correct potassium levels in the long term. It often requires re-treatment and can get very messy if the per rectum route is required.

This new compound, RLY5016, is a novel compound that acts as what was described as a "lumen sink" because it pulls potassium directly from the bloodstream into the distal colon. It is said to have twice the binding capacity of Kayexalate with a very tolerable side-effect profile, the worst of which was flatulence in 7% (well, depends on who we are referencing with regard to tolerability, the patient or his most unfortunate fellow human being who happens to be close at hand). There is a 6% incidence of hypokalemia, which we all know can be just as life-threatening, so recommendations for monitoring will be forthcoming. Also, there was some mention of a reduced 20-g dose option that would help avoid low potassium levels altogether, with available dosages up to 30 g.

Kayexalate has been in my medical armamentarium for nearly three decades, and I'm not sad to see it have some competition. The only concerns about the new treatment option expressed today included some issue with the distal colon where both magnesium and calcium concentrations are significant. There might also be some potential for leaching those elements, which might lead to such long-term theoretical issues as osteoporosis or acute issues such as hypocalcemia and hypomagnesemia. None of these issues, however, were noted in this short and very early study of this compound.

With the exception of a 30% decrease in the bioavailability of valsartan and rosiglitazone, the tolerability profile of RLY5016 is thus far excellent. I only hope that the long-term safety profile is just as excellent, and then perhaps this compound will be adequate therapy for those with a phobia of hyperkalemia and provide a mechanism by which heart-failure patients can obtain the lifesaving RAAS inhibition they so desperately need.

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Your comments

	PEARL-HF: RLY5016--A cure for hyperkalemia phobia and a help for needy CHF patients?
	# 1 of 2	August 30, 2010 04:21 (EDT)
	constantin rusu	I'm afraid Relypsa will only cure (hopefully) the fear of adding spironolactone to an ACE inhibitor/ ARB. It will do nothing on the "fear" of up-titrating the ACE inhibitor to full-dose. The scarecrow here is not that much the potassium level as it is the BP (a much prettier scarecrow, if you ask me). Maybe we need more trials like ATLAS, emphasizing the equal importance of quantity (and the overestimation of adverse events).
	# 2 of 2	August 30, 2010 05:13 (EDT)
	Melissa	Constantin, At this point, I'll take all the help I can get with this population of patients! Just discussing it is therapy in and of itself!  Thanks for posting! Melissa

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