Hyperkalemia: From the Inside Out

The video above may be viewed at hyperkalemiainsights.com

 

By Lance Berman, M.D., M.S.

Senior Vice President and Chief Medical Officer

Something that has always appealed to me is the opportunity to work in uncharted space, pursuing new avenues that have yet to be fully explored. Such opportunities are rare in the pharmaceutical industry, which is why investigating a new treatment for hyperkalemia has been so gratifying. When I joined Relypsa, the only indicated treatment for hyperkalemia had been developed over 50 years prior, with little progress since that time. In some ways, it was like a blank canvas.

Not many people have heard of hyperkalemia, or elevated blood potassium levels in the blood. If potassium levels get to high in the bloodstream, it can result in sudden and even fatal abnormal heart rhythms.1,2 The target blood potassium concentration range is considered to be 3.5 -5.0 mEq/L.2 Potassium is one of the essential electrolytes required for life, responsible for regulating electrical activity across cells, a process essential to helping the heart beat properly.2 However, too much or too little potassium is not a good thing. Hyperkalemia is the term used when potassium levels are too high, and hypokalemia is the term used when potassium levels are too low, and both can have serious consequences. To help keep potassium levels in check, the body has exquisite biological systems of regulation in place.

Maintenance of this system is called homeostasis, as the body works to maintain potassium levels in the bloodstream that are stable and appropriate.3 Interestingly, potassium is the most abundant cation (a positively-charged ion) in the body, but very little of it is actually found in the bloodstream.2 The vast majority of the potassium in our body, about 98% of it, is stored inside of our cells, to be released into the bloodstream as needed.2


“When I joined Relypsa, the only indicated treatment for hyperkalemia had been developed over 50 years prior, with little progress since that time. In some ways, it was like a blank canvas.”


Under normal conditions, the maintenance of a proper potassium concentration in the blood is not a problem; your body can handle it, no matter what you eat.4 Bananas come to mind for most people when considering foods that are rich in potassium, but artichokes and avocados contain more than twice as much. Whatever your preferred dietary source of potassium, however, it is the kidneys that remove most of the excess potassium from our bodies, about 90% of it, while the remainder is removed by way of the colon.2,3

Our total daily output of potassium should be about the same as our total daily intake, keeping the levels more or less balanced.5 In the presence of decreased kidney function, however, this system of homeostasis breaks down, and without the workhorse kidneys acting as our primary filter, potassium levels will inevitably begin to rise.6 This is why hyperkalemia is such an important issue for people with chronic kidney disease.

However, the body also has an elegant compensatory process to clear excess potassium that kicks-in if renal function is impaired.6 As potassium levels start to rise, the colon can actually compensate for the failing kidney through outlets called Big Potassium (or “Big K”) channels.5,7 These channels pump excess potassium into the lumen of the colon, where it can then be excreted along with the feces.7

This works for a while, but unfortunately, the colon cannot keep pace with excess potassium when the kidneys are not functioning properly. Clearance through the colon can compensate for only about 30 to 50 percent of the increase in potassium, and once these compensatory systems reach their limit, potassium levels will continue to rise.6 One possible approach to helping the body manage potassium levels is through assisted removal of excess potassium from the colon.1 In this way, potassium concentrations in the colon are maintained at a relatively low level, and sensing this, the Big K channels will keep pumping excess potassium into the colon.1

The exact level at which excess potassium will cause problems can vary greatly from patient to patient, and it is difficult to predict.6 This type of uncertainty motivates doctors to take preventative action. But in fact, options are fairly limited for these patients and a diet low in potassium is challenging to stick to. For people with progressive kidney disease especially, hyperkalemia can represent an ongoing risk that can be difficult to manage.

I am proud to be part a team of dedicated individuals here at Relypsa who are driven to find novel approaches to solve challenging health problems such as hyperkalemia. It has been quite a journey thus far, and there is more good work to be done as we continue to partner with other like-minded companies and healthcare professionals to discover, develop and deliver new medicines that can help improve patients’ lives.  

Lance joined Relypsa in December 2011 as Senior Vice President, Commercial Strategy and Medical Affairs, and was promoted in October 2012 to Senior Vice President and Chief Medical Officer.  Lance received his Bachelor of Medicine and Bachelor of Surgery at the University of Cape Town in Cape Town, South Africa, and holds a Masters Degree in Pharmaceutical Medicine.

References:

Bushinsky DA, et al., Kidney Int. 2015; Rastegar A, et al., Postgrad Med J. 2001;77:759-64. Giebisch GH, et al., Semin Nephrol. 2013;33:209-14; Khanna A, et al., Am J Med. 2009;122:215-21; 5 Welling PA,, Semin Nephrol. 2013;33:215-28; Evans KJ, et al., J Intensive Care Med. 2005;20:272-90; Sausbier M, et al.,  J Am Soc Nephrol. 2006;17:1275-82.