Phosphate-Binding Agents in Adults With CKD: A Network Meta-analysis of Randomised Trials. Suetonia C. Palmer, PhD, Sharon Gardner, MA, Marcello Tonelli, MD, Dimitris Mavridis, PhD, David W. Johnson, PhD, Jonathan C. Craig, PhD, Richard French, MBChB, Marinella Ruospo, MScMed, Giovanni F.M. Strippoli, PhD’Correspondence information about the author PhD Giovanni F.M. Strippoli Am J Kidney Dis 2016;68:691-702. 10.1053/j.ajkd.2016.05.015
Current Australian guidelines recommend 6-12 months assessment of PTH for patients with eGFR<45. What is the evidence for phosphate binders and which if any improve patient outcomes.
The combined effects of higher phosphate, lower calcium and lower vitamin D levels all serve to stimulate parathyroid hormone production, and in turn elevated levels of PTH increase the resorption and release of mineral from bone. It is reported that these changes have been associated with an increased risk of fracture and also increased cardiovascular mortality, perhaps mediated by accelerated vascular calcification.
- Network meta-analysis compare and rank phosphate-binder strategies for adults with CKD.
- Randomized trials with allocation to phosphate binders including
Sevelamer, lanthanum, iron, calcium, colestilan, bixalomer, nicotinic acid, and magnesium.
- The primary outcome was all-cause mortality. Additional outcomes were cardiovascular mortality, myocardial infarction, stroke, adverse events, serum phosphorus and calcium levels, and coronary artery calcification.
77 trials (12,562 participants) were included. Most (62 trials in 11,009 patients) studies were performed in a dialysis population. Trials were generally of short duration (median, 6 months) and had high risks of bias. All-cause mortality was ascertained in 20 studies during 86,744 patient-months of follow-up. There was no evidence that any drug class lowered mortality or cardiovascular events when compared to placebo. Compared to calcium, sevelamer reduced all-cause mortality (OR, 0.39; 95% CI, 0.21-0.74), whereas treatment effects of lanthanum, iron, and colestilan were not significant (ORs of 0.78 [95% CI, 0.16-3.72], 0.37 [95% CI, 0.09-1.60], and 0.55 [95% CI, 0.07-4.43], respectively). Lanthanum caused nausea, whereas sevelamer posed the highest risk for constipation and iron caused diarrhea. All phosphate binders lowered serum phosphorus levels to a greater extent than placebo, with iron ranked as the best treatment. Sevelamer and lanthanum posed substantially lower risks for hypercalcemia than calcium.
There is currently no evidence that phosphate-binder treatment reduces mortality compared to placebo in adults with CKD.