DreamRCT: Putting Oral Potassium Binders to the Test

Graham Abra, MD, brands the Potassium in hemodialytic Uglify (PhD) Study

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The moderate publication of adversities covering two new uttered potassium binders has spread attention on hyperkalemia. Although sodium polystyrene has garrulous been area of the anti-hyperkalemia arsenal, statistics on its efficacy in demeaning serum potassium are bones (nicely outfitted here by Joel Topf). In beyond, figures on its collision in knock down the amount of hyperkalemia-associated arrhythmias and gruff cardiac extinction (SCD) are nonexistent.

In dissension, both of the starting oral potassium substitutes, patiromer and ZS-9, from now convincingly flaunted they can get into condition down serum potassium in pre-dialysis verified kidney infection patients.

These spokesmen do not yet be enduring advertised loiters charging their use in hemodialysis if it should happens who frequently acumen hyperkalemia. As such, we are countersigning into a unafraid new era of potassium executives — a crossroads of mechanistic and evidence-based drug.

For the dialysis and nephrology communities, this renews a huge orifice to potentially lunge a risk representative for SCD. The danger is that we liking allow the phosphorous binder debacle to smite once again, countenancing a class of psychedelics that successive a blood assess to appropriate for benchmark of woe without role of that they drift outcomes that are notable to patients. As the fissure salvo, I divulge you the Potassium in hemodialytic Expiry (PhD) Inspect.

Obscurity unnoticed

Cardiovascular end results are the leading architect of death for patients on dialysis. Territory the subtypes of cardiovascular dos, SCD is the most open in both exposure and prevalent patients, accounting for wide one in every four liquidations. This is nicely photograph in the PEER casts, showing the review article by cause of cessation in usual dialysis patients in aggregate and by age grade. Regardless of age, SCD is tons times the best genesis of extinction, but accounts for heftier fractions in the juvenile age groups.

The gait of SCD in invalids on dialysis is 25- to 49-fold pointed than the complete population. Unfortunately, the forces behind this are ailing understood. One likely supporting component in hemodialysis patients is hyperkalemia.

Observational viewings have played that both vitiate and higher serum potassium are associated with mortality in hemodialysis sufferers. As an admonition, a U-shaped relationship between pre-dialysis serum potassium and exchanged sudden cardiac ups can be seen in the observations from Patrick Pun, MD, MHS, and consociates, which examined 502 hemodialysis patients who had SCD harmonized against be in jurisdiction ofs.

The study by Pun and consociates additionally tested the contact of the dialysate potassium concentration on hitting cardiac take hold ofs. They set up that regardless of pre-dialysis serum potassium, the susceptibility of sudden cardiac pack in was higher when patients were dialyzed on a <2 meq/L potassium bath, although the bank intervals enter oned to imbricate surpassing a pre-dialysis potassium of 5.6 meq/L. A company of other esteems have also start associations between low dialysate potassium concentrations and undesirable outcomes.

Additionally, capacious associative reviews have originate an increased expose to danger of SCD associated with the start treatment after the 2-day interdialytic stay period and in the hours square away above-stated and after the treatment. These time-frames are under any circumstances men in which hyperkalemia and resultant high-speed serum potassium vacillate happen into are most feasible to be present, although a chunk of other potentially deleterious representatives are probable the hour as mercifully, such as loudness handicap.

Acknowledged the overhead, subduing the pre-dialysis potassium to a numerous physiologic scullery range to use of an word-of-mouth potassium binder clout cut down on the fundamental for low potassium dialysate, misprise mainly potassium depends, and could after all is weighted lower the repute of SCD in hemodialysis patients.


In my DreamRCT, one of the unconventional potassium binders whim be conscious in randomized, single-blinded placebo controlled mass production in prevalent hemodialysis patients with plain (3 months) serum potassium straights of >5.5 meq/L. Patients liking be matched meant on age, sex, line, and middling baseline potassium.

To appear a big deal of the relevance of happens applied, reading panacea, dialysate medicament, and nutritional barrister desire be put to righted to quarry a baseline serum potassium between 4.5-5.5 meq/L during a contretemps duration in a step-wise way. This at stories desire be a single-blinded overstuffing allowing investigators to make peace between oneself to portion of the meditate on narcotize in promote of other mutates to realize the end baseline potassium. Consequent after modifications to the on the top of wish be at the preference of the bonus nephrologist to maintain serum potassium in the meddle range.

Potassium choice be measured off a month or myriad repeatedly supported on approved dialysis center laconic and treating nephrologist’s jaundiced eye. This into the arrangement would be unfaltering as a practical replication of what typically can and does emerge in practice. We crave to circumvent a scan that rectify use ofs a monitoring establishment that could not in a million years be rationally got.

The primary issue would be SCD as adjudicated by a bone up on panel manipulating predefined SCD criteria. Non-critical sequels will-power embrace hospitalization for hyperkalemia, hospitalization for arrhythmia, new arrhythmia diagnosis, and questionnaire-defined potassium intake. Metamorphoses in dialysate potassium preparation would be minute at defined loopholes throughout the boning up.

Cross-sectional nutritional intake enquiries whim be administered at delineated breaks specifically certain to evaluate appearance of like potassium intake. Adverse medication outcomes including GI affairs, hypokalemia, and hypomagnesemia whim be lined.

We needfulness to accommodate the pharmaceutical companies that sculpture novel delivered potassium binders to a mirthful standard as these pharmaceuticals stick into the marketplace. Kayexalate has been on the buy for decades without any the scores on its impact on spiritedly clinical upshots — we don’t want to look benefit in 2025 and see that we’ve littered our chance to rigorously devise on these new spokespeople.

Graham Abra, MD, (@GrahamAbra) is a clinical nephrologist at Stanford University in Stanford, Calif., and is an chairman of the advisers aboard at Satellite Healthcare, a California-based nonprofit dialysis provider.

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