Patiromer Trial in CKD Stage IIIB to V

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 lifesaving 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 - based on 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, particularly 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, particularly in non-dialysis patients with CKD stage IV to V. This hypothesis, however, must be tested in prospective randomized controlled trials.