The 2016 ERA-EDTA Congress featured two satellite symposia that highlighted the disease burden of hyperkalemia, as well as an oral session on mineral metabolism that discussed new potassium binder therapies (that are not approved at the time of writing in Europe).
Two satellite symposia included presentations on the challenges associated with managing potassium levels in CKD patients.
- Dr Johannes Mann discussed the epidemiology and mechanisms of hyperkalemia. He concluded that hyperkalemia is associated with increased mortality, and elevated serum potassium >5.5 mmol/l and >6.0 mmol/l is seen in ~10% and ~5% of patients with CKD stages 3-5, respectively. Several medications, low GFR and high urine protein can all indicate an increased risk of hyperkalemia, which is primarily driven by impaired renal potassium excretion.
- Dr Martin de Borst summarized current and emerging options for hyperkalemia treatment. Current options include dietary restrictions, sodium polystyrene sulfonate and restricted RAAS inhibitor use. However, all of these solutions have limitations and can lead to suboptimal management of other risk factors for CKD progression.
- Dr Matthew Weir highlighted that, although hyperkalemia is often a limiting factor for the use of RAAS inhibitors in CKD patients, new potassium binding agents are being developed which may allow patients who have been previously unable to tolerate RAAS inhibition to benefit from this important treatment option.
New compounds that are proposed for hyperkalemia treatment include zirconium cyclosilicate and patiromer. Both have met efficacy and safety endpoints in clinical trials, but await both longer-term safety results and EMA approval.
Two oral presentations at the ERA-EDTA 206 Congress reported data on the novel potassium binder, patiromer, which has been approved by the FDA and has been submitted for marketing approval by the EMA.
A sub-analysis of the AMETHYST-DN Phase II study of patiromer in diabetic kidney disease patients focused on a sub-group of patients on RAASi therapy. Results of this analysis were presented by Dr Murray Epstein. 56 patients were identified as receiving either dual therapy (both an ACE inhibitor and an ARB) or combined therapy (ACE inhibitor and/or ARB with a mineralocorticoid receptor antagonist). Of these patients, 41 had mild and 15 had moderate hyperkalemia. “Clinically significant decreases in mean serum potassium with patiromer were observed at the first post-baseline assessment on day 3 and were sustained throughout 52 weeks.” Patiromer was generally well tolerated in the study.
A pilot study of patiromer in healthy subjects was also presented. Dr David Bushinky hypothesized that patiromer could also bind to sodium in the gastrointestinal tract, reducing the risk of volume overload and thus hypertension in CKD patients. A study of 32 healthy subjects receiving patiromer showed a dose-related decrease in urine excretion of sodium, supporting the hypothesis that patiromer binds both sodium and potassium in the gastrointestinal tract.
- Epstein M, Mayo M, Garza D, et al. SO010 – Patiromer Protected Against Recurrent Hyperkalemia for up to 52 Weeks in Patients with Diabetic Kidney Disease Receiving Combined RAAS Inhibitor Therapy. Nephrol Dial Transplant. 2016;31(suppl 1):i4-i4. doi:10.1093/ndt/gfw118.05.
- Bushinsky DA, Spiegel DM, Benton W, et al. SO008 – Effect of the Potassium Binding Polymer Patiromer on Urine Sodium Excretion in Healthy Adults. Nephrol Dial Transplant. 2016;31(suppl 1):i3-i4. doi:10.1093/ndt/gfw118.03.