Authors’ Reply: Calcium-Based Phosphate Binders and Plasma Oxalate Concentration in Dialysis Patients

We thank Oka and colleagues for their comments on our paper and their suggestion for a possible role for alternative therapeutic interventions to reduce oxalate concentrations and cardiovascular mortality in patients on dialysis. They suggest a low-oxalate diet or calcium-based phosphate binders could decrease oxalate absorption and lead to reduced cardiovascular risk. We agree these measures warrant further evaluation when planning interventional studies examining elevated plasma oxalate concentrations and risk of sudden cardiac death in patients on dialysis. Avoidance of high-oxalate foods makes sense, although the dietary restrictions faced by patients on dialysis are already burdensome.¹ Of note, food products high in potassium often contain high amounts of oxalate (nuts, beans, certain vegetables).² The current Kidney Disease Improving Global Outcomes guidelines³ suggest restricting the dose of calcium-based phosphate binders in adults with CKD stage G3a–G5D receiving phosphate-lowering treatment (2B recommendation), due to a higher mortality risk. For patients on dialysis, this recommendation was made on the basis of a large trial comparing sevelamer to a calcium-containing phosphate binder.⁴ The eight trials analyzed by Jamal et al.,⁵ and duly cited by Oka and colleagues, also compared sevelamer with calcium carbonate or acetate. Yet, sevelamer itself may also feature a modest oxalate-lowering effect, as shown in a small trial in patients with enteric hyperoxaluria.⁶ Future studies could elucidate this issue further.

Disclosures

F. Knauf reports receiving personal fees from Advicenne, Allena Pharmaceuticals, Alnylam Pharmaceuticals, Fresenius Medical Care, Oxthera Pharmaceuticals, and Sanofi Pharmaceuticals, outside the submitted work; receiving honoraria from Advicenne, ECoR1, Medice, and Sanofi; receiving research funding from Alnylam Pharmaceuticals, Dicerna Pharmaceuticals, Deutsche Forschungsgemeinschaft, and Else Kröner Fresenius Stiftung; having consultancy agreements with Chinook Pharmaceuticals USA, EcoR1 USA, and Zai Pharmaceuticals China; serving on the scientific advisory board of the Oxalosis and Hyperoxaluria Foundation NYC; and having patents or royalties with PocketDoktor Medical Books. F. Knauf and A. Pfau report being employees of the nonprofit institute Charité-Universitätsmedizin Berlin, which has recently filed a patent for oxalate-lowering agents in patients on dialysis, with A. Pfau and F. Knauf listed as inventors. A. Pfau reports receiving personal fees from Alnylam Pharmaceuticals, outside the submitted work.

Funding

None.

Author Contributions

F. Knauf provided supervision, reviewed and edited the manuscript, and was responsible for validation; and A. Pfau conceptualized the idea of this manuscript, wrote the original draft, and was responsible for investigation.