Refractory hyperkalemia is among the leading causes of initiation or chronic renal
replacement therapy (RRT) by extracorporeal or peritoneal dialysis in patients with chronic
kidney disease (CKD). Dialysis therapy is life-saving, but has a major impact on patients'
quality of life and is terribly expensive. Thus, deferring dialysis initiation by preventing
hyperkalemia would have major implications for patients and health care providers.
Among patients with CKD, glomerular filtration rate (GFR) <45 ml/min/1.73 m2, older age,
coexistence of diabetes or heart failure, and inhibition of the renin angiotensin aldosterone
system (RAAS) by angiotensin-converting-enzyme (ACE) inhibitors, angiotensin receptor
blockers (ARBs) or aldosterone antagonists are the major risk factors for hyperkalemia. On
the other hand, RAAS inhibitors - on the basis of randomized trial results showing the
superior effect of these medications compared to other antihypertensive drug classes in
slowing the progression of chronic nephropathies to end-stage renal disease (ESRD) - are
first-line therapy for patients with CKD, in particular for those with proteinuric
nephropathies.
However, the risk of hyperkalemia is a major impediment to adequate RAAS blockade in CKD,
especially when RAAS inhibitors are used in maximal doses or are combined.
Dietary counseling, correction of metabolic acidosis and treatment with loop diuretics are
key components of potassium-lowering therapy in patients with CKD. Combined therapy with
potassium binders, however, is often needed to prevent or treat hyperkalemia, in particular
in patients with GFR <45 ml/min/1.73 m2, concomitant diabetes and/or RAAS inhibitor therapy.
A newer potassium binder, patiromer, has been approved by FDA and EMA for the treatment of
hyperkalemia. Patiromer is an organic, non-absorbed, sodium-free, potassium-binding polymer
that exchanges potassium for calcium in the gastrointestinal tract. Because of the remarkably
good risk/benefit profile, it is conceivable that patiromer may safely improve hyperkalemia
control and reduce the need of RAAS inhibition interruption or down-titration (not only of
ACE inhibitors and ARBs but also of potassium sparing diuretics such as spironolactone,
eplerenone and finerenone) in patients with severe CKD. In turn, this could translate into
improved nephroprotection and deferred initiation of dialysis, in particular in non-dialysis
patients with CKD stage IV to V. This hypothesis, however, has to be tested in prospective
randomized controlled trials.
Phase:
Phase 3
Details
Lead Sponsor:
Mario Negri Institute for Pharmacological Research