Balancing the cardio-renal benefits of RAASi therapy against the risks of hyperkalaemia in CKD patients is a significant challenge. ERA-EDTA 2017 provided an update on this topic, along with the status of novel potassium (K+) binders and their role in maintaining RAASi use. This article gives an overview of the key presentations and posters from the recent congress.
Benefits and risks of RAAS inhibition (RAASi)
Multiple presentations focused on the benefits of RAASi therapy and the increased associated risks of hyperkalaemia.
In an oral presentation on Sunday, Dr Matthew Weir examined the potential benefits of treatment with mineralocorticoid receptor antagonists (MRAs) in patients with heart failure. MRAs are an important therapy for HFrEF patients (HF with reduced ejection fraction) but are associated with an increased risk of hyperkalaemia, with the rates seen in real-world studies significantly higher than those reported in randomised controlled trials. The difficulties in balancing risk and benefit were highlighted by data showing that in patients with severe heart failure, treatment with an MRA improved survival vs placebo, even in the presence of moderate hyperkalaemia.
RAASi data from the DOPPS study was analysed in multiple posters:
- Dr Xu et al. assessed variations in RAASi prescriptions according to serum K+ levels, comorbidities and geography over time; overall, patients with diabetes and hypertension were more likely to receive RAASi prescription vs those without. They noticed that RAASi may be underprescribed in patients who would most benefit from this treatment, particularly CHF patients.
- Dr Karaboyas and colleagues found that in haemodialysis patients, RAASi prescription was associated with lower adjusted all-cause mortality in both incident (HR=0.87; 0.79-0.96) and prevalent (HR=0.93; 0.89-0.98) haemodialysis, compared to no RAASi prescription.
The risks of hyperkalaemia in CKD patients were discussed in several posters and oral presentations on both Sunday and Monday. These included:
- A Danish prospective cohort study which found that 23% of CKD patients had a hyperkalaemic event in a 4-year period; patients with heart failure, diabetes and/or treated with ACE-inhibitors or spironolactone were at highest risk for developing hyperkalaemia
- A UK retrospective study which assessed that physicians were more likely to discontinue RAASi in CKD patients with high serum K+levels
- Another analysis of the same UK retrospective database found that patients with an initial severe hyperkalaemic event had a higher incidence of all-cause hospitalisation, decline in kidney function and all-cause mortality versus those with a mild or moderate hyperkalaemic event. Severe hyperkalaemia was defined as K+ >6.0 mmol/L or a diagnosis code, regardless of K+ level
Novel potassium binders
Two novel potassium binders, patiromer and ZS-9, were also discussed in several presentations.
In the oral session Heart failure in chronic kidney disease, Dr Weir reviewed the current hyperkalaemia treatment landscape (excluding emergency treatment). Current options include dietary restrictions, potassium removal during dialysis, and potassium binders such as kayexalate (sodium polystyrene sulfonate). However, their use is hindered by individual limitations: the prevalence of potassium can lead to healthy foods being excluded from a diet; a longer time required for dialysis and warnings for kayexalate relating to serious GI events and increases in sodium levels. Dr Weir went on to present data on patiromer (a non-absorbed polymer that binds K+) in HK patients on continuous RAASI therapy. Results showed a significant reduction in serum K+ from baseline. At week 4, 76% of patients achieved a serum K+ within target range.
During a free communication session, Dr David Bushinsky presented a pooled analysis of the OPAL-HK and AMETHYST-DN clinical trials, evaluating the efficacy and safety of patiromer in patients receiving one or more RAAS inhibitors across CKD stages 3 to 5. The change from baseline in serum potassium during the first four weeks of patiromer treatment was reduced by a similar amount in three eGFR subgroups (<15, ≥15-<30, and ≥30 mL/min/1.73 m2). Dr Bushinsky concluded that, in patients receiving RAASi therapy, patiromer is effective and well tolerated across CKD Stages 3-5, irrespective of the presence of diabetes.
Data on both ZS-9 and patiromer was also presented in two industry symposia, confirming efficacy and safety results from Phase III randomised controlled trials.[8,9]
- Mineralocorticoid receptor blockers in CKD patients. Matthew Weir. Symposium presentation – ERA-EDTA 2017 Congress
- [MP385] Renin-angiotensin-aldosterone system inhibitor prescription patterns in haemodialysis patients: results from the international Dialysis Outcomes and Practice Patterns Study (DOPPS). Hairong Xu et al. ERA-EDTA 2017 Congress
- [SP551] Renin-angiotensin-aldosterone system inhibitors (RAASi) and clinical outcomes in hemodialysis patients: results from the DOPPS. Angelo Karaboyas et al. ERA-EDTA 2017 Congress
- [MO066] Elevated potassium levels in patients with chronic kidney disease. Incidence, risk factors and clinical outcomes. Reimar Thomsen et al. ERA-EDTA 2017 Congress
- [MP373] The relationship between serum potassium concentration and discontinuation of renin-angiotensin-aldosterone system inhibitors in UK patients with CKD. Lei Qin et al. ERA-EDTA 2017 Congress
- [MP380] CLINICAL OUTCOMES ASSOCIATED WITH HYPERKALAEMIA IN ADULTS IN THE UK. Laura Horne et al. ERA-EDTA 2017 Congress
- Treatment of hyperkalaemia in dialysis patients: what is on the horizon? Matthew Weir. Symposium presentation – ERA-EDTA 2017 Congress
- Optimising RAASi therapy in cardio-renal patients through hyperkalaemia management. Industry Symposium. ERA-EDTA 2017
- Hyperkalaemia in CKD: An Evolving Treatment Landscape. Industry Symposium. ERA-EDTA 2017