REVIEW Phosphate binders in CKD: chalking out the differences Lesley Rees & Rukshana C. Shroff Received: 16 July 2009 / Revised: 15 August 2009 / Accepted: 18 August 2009 / Published online: 7 November 2009 # IPNA 2009 Abstract Plasma phosphate levels are important in the evolution of hyperparathyroidism and ectopic calcification in chronic kidney disease (CKD). Although dietary management may be adequate to control plasma phosphate in its early stages, most patients develop hyperphosphataemia by CKD stages 3-4 and require the addition of a phosphate binder. Calcium-containing phosphate binders are the most used and cheapest binders but have fallen out of favour because of the potential for positive calcium balance and calcium toxicity. This problem may be attenuated by newer phosphate binders such as sevelamer hydrochloride and lanthanum carbonate. In this review, the role of phosphate as a uraemic toxin and the advantages and disadvantages of the currently available phosphate binders are discussed. Keywords Children . Phosphate . Calcium . Phosphate binders . Calcium carbonate . Calcium acetate . Sevelamer . Lanthanum Introduction Phosphate has probably the best described spectrum of toxicity of all molecules that circulate in excess in chronic kidney disease (CKD). Decreased renal phosphate excretion plays a major role in the onset of hyperparathyroidism. Furthermore, plasma phosphate levels are positively and independently correlated with an increasing risk of death from cardiovascular disease [1]. However, despite these clear associations, control of our patients’ plasma phosphate is one of our most challenging management issues, and indeed, some physicians believe that a high plasma phosphate is an inevitable consequence of CKD, accepting that good phosphate control is an impossible task. The role of phosphate in the evolution of hyperparathyroidism Phosphate is filtered at the glomerulus and reabsorbed in the proximal tubules, with approximately 85% of the filtered phosphate reabsorbed via the sodium-phosphate cotransporter IIa located in the proximal tubular brush- border membranes. It would be expected, therefore, that CKD would result in hyperphosphataemia. However, we now know that compensatory mechanisms act to preserve a normal plasma phosphate in early CKD. The molecules responsible for this are fibroblast growth factor-23 (FGF-23), a hormone produced by the osteocyte; and Klotho, a single-pass transmembrane protein. FGF-23 requires Klotho as an obligatory coreceptor to activate FGF signalling. Together they result in negative phosphate balance by decreasing renal tubular phosphate reabsorption and by suppressing the renal 1-α hydroxylase receptor, thereby reducing the synthesis of 1,25-dihydroxyvitamin D [1,25(OH) 2 D]. This, in turn, decreases gastrointestinal phosphate absorption [2]. The sequence of events that stimulate this process is not yet known: it could be that decreased Klotho expression from renal damage stimulates an increase in FGF-23 to L. Rees : R. C. Shroff Department of Nephrology, Great Ormond Street Hospital for Children NHS Trust, London, UK L. Rees (*) Renal Office, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, UK e-mail: Reesl@gosh.nhs.uk Pediatr Nephrol (2010) 25:385–394 DOI 10.1007/s00467-009-1329-0