The promise of new drugs against hyperkalemia

Matthew R. Weir, MD, is director of the division of nephrology and professor of medicine at the University of Maryland School of Medicine in Baltimore. Dr. Weir was the principal investigator of a clinical trial that demonstrated patient safety and efficacy in the treatment of hyperkalemia in patients with renal disease receiving renin-angiotensin-aldosterone system (RAAS) inhibitors and participated in other trials Of the patient. Patiromer recently received FDA approval for the treatment of hyperkalemia. He spoke to Renal & Urology News about which patient and another hyperkalemic drug in the pipeline, Zirconium Cyclosilicate Sodium (ZS-9), could mean for future patient care.

What are some of the unresolved problems in the treatment of hyperkalemia?

Dr. Weir: The main question is really the best way to deal with it. Acute management is not going to change. Chronic management is much more important. What most doctors do is give sodium polystyrene sulfonate and stop or reduce the dose of RAAS [renin-angiotensin-aldosterone] inhibitors. They will do anything and everything they can to avoid problems. The problem is that we do not have a safe and well tolerated strategy to treat chronic hyperkalemia. Even if people have heart failure or kidney failure, doctors opt for the most appropriate therapy.

I honestly think we have to address this. For our patients with renal disease and heart disease, it will be important for us, clinically, to advance, devise a strategy to increase the use of RAAS-ACE inhibitors, angiotensin receptor blockers and mineralocorticoid receptor antagonists. If these agents [Patiromer and ZS-9] prove to be as safe and effective as they appear to be in clinical trials, they can actually open the window to optimize RAAS block or aldosterone block even in people with chronic kidney disease.

What is the incidence of hyperkalemia among patients with chronic kidney disease (CKD) in RAAS inhibitors?

Dr. Weir: It depends on how advanced kidney disease is. It could be as much as half of all patients, if not more. In my practice, it is at least 20% to 25%.

Do you think that patiromer and zirconium-sodium cyclosilicate (ZS-9), which is in clinical trials, can improve the management of CKD?

Dr. Weir: Absolutely. I really think they will make a difference. The reason is that they are well tested, they seem to be very safe, and I think there will be a greater awareness of a topic that has been neglected for a long time just because there were no adequate treatment strategies.

How do Patiromer and ZS-9 compare? Are there advantages and disadvantages compared to the other?

Dr. Weir: There are no direct studies comparing them. As I look at clinical data, they appear to be very similar in overall efficacy. ZS-9 has a faster onset of action, which I do not think makes a difference in chronic care because it binds potassium higher in the intestine, while the patiromer works more in the colon. You can see the effects of ZS9 in 2 hours, while with patiromer, more like 4 or 5 hours. Both are powder substances that are tasteless and odorless and dissolved in water.

The only major difference I see is that patiromer calcium exchanges, while ZS-9 exchanges sodium. That can make a difference in terms of long-term effects on blood pressure. More studies are needed to clarify the possible differences between these drugs in this regard.

One of the potential complications of these new drugs is that they can be linked to other medications. What is your opinion on that?

Dr. Weir: In vitro tests showed that the patient binds to a number of different drugs. It is not known whether this has clinical relevance. For example, patiromer binds to furosemide, metroprolol and amlodipine, which are probably 3 of the most common drugs we use in patients with CKD. However, in clinical studies, systolic blood pressure drops by approximately 5 mm Hg. The FDA has strongly suggested that there be a 6-hour window between dosage of medication and use of patiromer. I do not know if ZS-9 will have a similar restriction or not.

What do you see as the ideal drug for hyperkalemia?

Dr. Weir: Safe, effective and well tolerated. Cost can be a problem. I suspect that these drugs will come out with price points comparable to phosphate binders.