Highlights Related to Hyperkalemia, Hyperphosphatemia, and Renal Anemia

The annual ERA-EDTA conference showcases the latest and best research across all things nephrology from around the world and its 55th meeting, held in Copenhagen, Denmark, was no different. Here are just a few highlights related to chronic kidney disease (CKD) complications, such as hyperkalemia, hyperphosphatemia, and renal anemia.


The RAAS to Improve Hyperkalemia Management

Inhibition of the renin-angiotensin-aldosterone system (RAAS) is a key strategy in treating hypertension, cardiovascular, and renal diseases. However, RAAS inhibitors increase the risk of hyperkalemia. At ERA-EDTA, few studies examined the relationship between the management of hyperkalemia and the use of RAAS inhibitors.

  • Data from an observational study included 1-year incidence rates for hyperkalemia amongst patients receiving mineralocorticoid receptor antagonists (MRAs). According to the authors, over 18% of patients developed hyperkalemia within the first year, the majority occurring within the first three months. Close to half of the patients who experienced a moderate/severe hyperkalemia event had their MRA discontinued. Furthermore, dose reduction was seen in 10% of the patients.1
  • Moderate and severe hyperkalemia events among RAAS inhibitor users in the United Kingdom were reported in another study. The authors noted a rate of 11.5 and 12.3 per 100 patient-years in those with CKD stage 4 and stage 5, respectively.2
  • New research emphasized how hyperkalemia development can lead to the suboptimal use of RAAS inhibitors. The observational study in patients with CKD stage 3+ in the United Kingdom highlighted that two-thirds of patients did not receive the full European Society of Cardiology-recommended dose of any RAAS inhibitors, and that the adjusted odds ratio of a RAAS inhibitor dose down-titration or discontinuation increased with the severity of hyperkalemia.3


Potential Potassium Potions

Recently, novel hyperkalemia therapies such as Vifor FMC Renal Pharma’s Veltassa and Astra Zeneca’s Lokelma have demonstrated long-term efficacy and safety in controlling serum potassium levels in patients with a history of hyperkalemia complications. At ERA-EDTA, several studies investigated the outcomes of these drugs in patients with other comorbidities.

  • One study analyzed the effect of Veltassa on serum potassium levels in hyperkalemia patients with and without obesity. They pooled data from AMETHYST-DN, OPAL-HK and TOURMALINE studies and concluded that treatment with Veltassa resulted in a similar reduction in serum potassium levels over time in both patient groups.4
  • A retrospective analysis of data from a Phase III study of Lokelma compared the efficacy and safety in hyperkalemia patients with and without diabetes. Lokelma was similarly effective in both patient groups, reducing serum potassium levels and maintaining normokalaemia for up to 12 months.5 Further analysis of this study suggested that Lokelma treatment reduced serum potassium levels and maintained normokalaemia up to 12 months in groups with eGFR<30 and eGFR≥30 mL/min/1.73 m2.6


Finally, Phosphate Findings

Hyperphosphatemia plays a critical role in the development of secondary hyperparathyroidism and renal osteodystrophy in patients with late-stage CKD. Achieving optimal phosphate control in late-stage patients is extremely challenging. Despite an increase in the number of phosphate binders available and improvements in dialysis techniques over the years, phosphate control has not greatly improved. However, results shared at the ERA-EDTA suggest that manufacturers of new iron-based phosphate binders such as Vifor FMC Renal Pharma’s Velphoro and Keryx’s Auryxia are looking to establish themselves with benefits beyond just lowering phosphate levels.

  • Analysis of the first 18 months of the VERIFIE trial suggests real-life use of Velphoro lowers phosphate levels in dialysis patients, regardless of prior dialysis duration, previous phosphate binder treatment, or concomitant phosphate binder use.7 Further analysis of the same trial found Velphoro to be well-tolerated, with most adverse drug reactions being gastrointestinal-related and with no new safety risks.8
  • Data from EuCliD5 showed that Velphoro can significantly improve control of serum phosphate with a reduced pill burden (from 5.1 at baseline to 3.9 pills/day in months 4-6 in patients switched from another phosphate binder).9
  • Results from the Phosphate Normalization Trial of fixed-dose ferric citrate compared to standard of care in patients with progressive CKD demonstrated that regardless of baseline, Auryxia significantly increased iron stores and hemoglobin (Hb) levels, and decreased phosphate levels. Authors also suggested a benefit in time to death, dialysis or transplant for those assigned to ferric citrate in the total cohort and among the diabetic patient sub-group.10


Real World Results for Renal Anemia

Using data from the Dialysis Outcomes and Practice Patterns database, investigators studied incident hemodialysis patients with a Hb ≥10 g/dL at 4 months, who also had a Hb level recorded within the first month of dialysis. Of the 4,461 patients, over half had Hb <10 g/dL when starting dialysis. The study results suggested that that the effective management of anemia before initiation of dialysis may improve survival during the first year. Hb levels at the start of dialysis were inversely associated with mortality in months 5-12.11



1 Incidence, predictors and clinical management of hyperkalemia in new users of MRAs. [sao024]

2 Rates of hyperkalemia among individuals receiving RAAS inhibitors. [sp324]

3 Relationship between hyperkalemia and down-titration or discontinuation of RAAS inhibitors in UK patients with CKD. [fp337]

4 Effect of patiromer on serum potassium in hyperkalemic patients with and without obesity: pooled results from the AMETHYST-DN, OPAL-HK and TOURMALINE trials. [fp102]

5 Sodium zirconium cyclosilicate for hyperkalemia in patients with diabetes mellitus: retrospective analysis of a 12-month open label, Phase III study. [sp421]

6 Safety and efficacy of sodium zirconium cyclosilicate for long-term treatment of hyperkalemia in patients with CKD: results from an open-label, Phase III study. [fp071]

7 Real-world effectiveness of sucroferric oxyhydroxide for serum phosphorus control in dialysis patients: an interim subgroup analysis of the VERIFIE study. [fo047]

8 Real-world safety and effectiveness of sucroferric oxyhydroxide in dialysis patients: an interim analysis of the VERIFIE study. [fp593]

9 Evaluating the real-world effectiveness of sucroferric oxyhydroxide in hemodialysis patients: a retrospective database analysis. [fp611]

10 Randomized trial of the effects of ferric citrate in patients with advanced CKD. [lb05]

11 Is low Hb at hemodialysis initiation associated with first-year survival among patients treated to target levels soon after dialysis start? [sp340]

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