Elevated Phosphorous in CKD: How to Avoid Vascular Calcification

Gregory W. Rutecki, MD

Dr Rutecki is with the Cleveland Clinic National Consultation Service.

The optimal choice of medication to bind excess phosphate in patients with advanced CKD won't always be straightforward.

Decreased renal function leads to an elevation in serum phosphorus levels. As a result, many patients with chronic kidney disease (CKD) are prescribed phosphate binders to decrease absorption of phosphate from the gastrointestinal tract. From a cardiologist’s perspective, the phosphate abnormality translates into increased cardiovascular calcification as well as increased cardiovascular morbidity/mortality. In fact, in patients with end stage renal disease (ESRD), hyperphosphatemia is an independent risk factor for death.

A recent review in the Cleveland Clinic Journal of Medicine is an excellent update on the treatment of hyperphosphatemia as well as on the myriad cardiovascular implications.

In the majority of CKD 5 patients, dialysis does not remove enough phosphorus to normalize serum levels, necessitating use of phosphorus binders. Binders are categorized into 2 groups: those containing and those without calcium. The two most commonly used calcium-containing binders are calcium carbonate and calcium acetate. Non-calcium binders are lanthanum, sevelamer, sucroferric oxyhydroxide, and ferric citrate. There is an important clinical difference between the 2 binder groups. Two randomized controlled trials compared sevelamer to calcium-based binders. The risk of vascular calcification was higher in both studies with the calcium-containing agents. Fetuin A, a specific serum agent, is an inhibitor of vascular calcification and is decreased in CKD. Sevelamer increases fetuin A. More definitive data in this regard are lacking.

Unfortunately, there are other important variables impacting phosphate binder choice. Expense is one. Two hundred calcium acetate pills are approximately $105.1 In contrast, 200 lanthanum pills are $2,880 (sucroferric oxyhydroxide is almost exactly the same cost). Sucroferric oxyhydroxide and ferric citrate also increase iron stores. This translates into a decreasing requirement for parenteral iron and erythropoietin in some dialysis patients.

Longer-term benefits of the non-calcium based binders-including vascular benefits-have not been completely proven. Presently, non-calcium based binders should be the agents of choice in patients with CKD and hyperphosphatemia and any of the following: complicated diabetes mellitus, vascular or valvular calcification, and persistent inflammation. The area remains a work in progress.

Source: Sekar A, Kaur T, Nally JV, et al. Phosphorus binders: The new and the old, and how to choose. Clev. Clin. J. Med. 2018; 85:629-638.