Date of publication: December 11, 2017

News & Views

ASN Kidney Week 2017: The Impact of Hyperkalemia on RAASi Use and New Data on Novel Potassium Binders

At the American Society of Nephrology’s Kidney Week 2017 congress in New Orleans, results from several studies looking at the prevalence and impact of hyperkalemia were presented, alongside data for new therapies which may allow greater use of renin-angiotensin aldosterone system inhibition (RAASi) in patients with CKD and cardiac disease.

Prevalence and impact of hyperkalemia

Several presentations at Kidney Week 2017 focused on the prevalence of hyperkalemia in the US. Data from the international CKDopps cohort was also analysed to assess RAASi usage in moderate to advanced CKD, alongside concomitant medications such as potassium binders.

Using the extensive US Medicare data resource, researchers calculated the prevalence of hyperkalemia in the elderly (>65yrs) population in the US, stratified by concomitant disease.[1] They reported a rate of 2.6%-2.7% in the overall Medicare sample, with a rise to 10.8%-12.4% in those with CKD and 50.2%-52.8% in those undergoing dialysis. Heart failure, diabetes, and hypertension were also associated with significant increases in the risk of hyperkalemia. Scaling up to consider the total US elderly population, this equates to an annual incidence of hyperkalemia of 1-1.1 million in this group.[1]

In a poster presentation, Macedo et al. examined hospital records and found that 8% of hospitalized patients had at least two hyperkalemic measurements (serum potassium >5mmol/L). The investigators also analysed the occurrence of complicated hyperkalemia, which was associated with increased length of hospital stay and high mortality, and identified “clinical and process of care factors” which can help identify patients at highest risk for complications.[2]

In an oral session, Dr Pecoits-Filho, Brazil, presented an analysis of the international CKDopps cohort, testing the hypothesis that RAASi treatment may be underused in CKD patients, potentially due to risks of hyperkalemia.[3] Examination of RAASi prescription patterns in Brazil, France, Germany and USA for patients with eGFR 15-45 ml/min showed that RAASi use varied between countries, but was consistently lower in the US for all indications. Only 54% of patients in the US with any indication for RAASi prescription received treatment. Potassium binder use was uncommon in all countries, but particularly low in the USA and Brazil.[3]

New data and new options in hyperkalemia management

Two new potassium binders have the potential to support RAASi dosing to an optimal level. Several presentations at Kidney Week 2017 presented new study data on these therapies.

Using real-world data from patients receiving dialysis at Fresenius Kidney Care centres in the US, Chatoth et al. analysed serum potassium (s[K+]) levels in the 6 months following initiation of patiromer, a potassium binder. The average s[K+] at baseline was 5.8 mEq/L, which was reduced by 0.3 mEq/L by week 1 of treatment, remaining reduced at 5.3 mEq/L at 6 months. When patients were stratified by baseline s[K+], those with the highest baseline levels experienced the greatest reduction. The decrease in s[K+] was achieved with minimal dose adjustments from the initiated dose of 8.4 g/day.[4]

In an oral session, Dr David Bushinsky, USA, presented data from TOURMALINE, an open-label, randomized trial comparing administration of patiromer with and without food in hyperkalemic patients with diabetes, heart failure, hypertension and/or CKD.[5]

After 4 weeks of patiromer treatment:

  • Serum calcium remained unchanged
  • Serum 1,25(OH)2D was significantly reduced
  • Parathyroid hormone levels were significantly reduced
  • FGF23 or 25(OH)D remained unchanged
  • Serum phosphorus was significantly reduced in patients with hyperphosphataemia at baseline[5]

Bushinksy et al. concluded that the study results are suggestive of the mechanism of action; when patiromer exchanges intestinal K for calcium, some of the released calcium binds to intestinal phosphorus lowering serum phosphate in hyperphosphatemic patients, and some of the calcium is absorbed, lowering PTH and 1,25(OH)2D. Serum calcium levels remain unchanged.[5]

Several studies into a potential new treatment for hyperkalemia, sodium zirconium cyclosilicate (ZS-9), also featured at this year’s ASN Kidney Week. Most notably, Fishbane et al. presented data from a long-term, Phase III study of ZS-9. This study included an acute treatment phase (ZS-9 10 mg three times a day for 24-72 hrs) followed by an extended stage (up to 12 months) for those patients who achieved s(K+) ≤5.0 mEq/L during the acute period.[6]

Acute treatment resulted in a mean reduction in s[K+] of -0.85 mEq/L, which was maintained throughout the extension period. In the 3-12 months period, 77.9% of patients had s[K+] ≥3.5 and ≤5.0 mEq/L, while 98.7% of patients had s[K+] ≥3.5 and ≤5.5 mEq/L. The mean dose required to maintain normokalemia was 7.2 g/day. There was a low incidence of hypokalemia (5.8% of patients).[6] However, peripheral oedema occurred in 9.7% of patients and hypertension in 11%.[6]

References

  1. Prevalence of Hyperkalemia in Medicare Patients. Brett KA. et ASN Kidney Week 2017, SA-PO430.
  2. Clinical Determinants of Complicated Hyperkalemia in Hospitalized Patients. Macedo E. et al. ASN Kidney Week 2017, SA-PO046.
  3. Are RAASi Underused in Moderate to Advanced CKD? Early Findings from CKDopps. Oral Session: CKD-CV Axis: Epidemiology and Outcomes. Pecoits-Filho R. et al. ASN Kidney Week 2017, FR-OR018.
  4. Outcomes in ESRD Patients on Hemodialysis Taking Patiromer for Hyperkalemia. Chatoth DK. et ASN Kidney Week 2017, TH-PO779.
  5. Effects of the Potassium Binding Polymer Patiromer on Markers of Mineral Metabolism. Oral Session: Mineral Disease: FGF23 and Mineral Metabolism. Bushinsky DA. et al. ASN Kidney Week 2017, FR-OR068.
  6. Maintained Efficacy and Safety of Sodium Zirconium Cyclosilicate for Hyperkalemia: 12-Month, Open-Label, Phase 3 Study. Fishbane S. et al. ASN Kidney Week 2017, TH-PO1112.

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