SAGE-Hindawi Access to Research International Journal of Nephrology Volume 2011, Article ID 970245, 6 pages doi:10.4061/2011/970245 Review Article Phosphate Metabolism in CKD Stages 3–5: Dietary and Pharmacological Control Markus Ketteler Division of Nephrology, Klinikum Coburg, 96450 Coburg, Germany Correspondence should be addressed to Markus Ketteler, markus.ketteler@klinikum-coburg.de Received 21 December 2010; Accepted 14 March 2011 Academic Editor: Domenico Russo Copyright © 2011 Markus Ketteler. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. When compared to the available information for patients on dialysis (CKD stage 5D), data on the epidemiology and appropriate treatment of calcium and phosphate metabolism in the predialysis stages of chronic kidney disease (CKD) are quite limited. Perceptible derangements of calcium and phosphate levels start to become apparent when GFR falls below 30 mL/min in some, but not all, patients. However, hyperphosphatemia may be a signiﬁcant morbidity and mortality risk predictor in predialysis CKD stages. The RIND study, evaluating progression of coronary artery calciﬁcation in incident hemodialysis patients, indirectly demonstrated that vascular calciﬁcation processes start to manifest in CKD patients prior to the dialysis stage, which may be closely linked to early and invisible derangements in calcium and phosphate homeostasis. Novel insights into the pathophysiology of calcium and phosphate handling such as the discovery of FGF23 and other phosphatonins suggest that a more complex assessment of phosphate balance is warranted, possibly including measurements of fractional phosphate excretion and phosphatonin levels in order to appropriately evaluate disordered metabolism in earlier stages of kidney disease. As a consequence, early and preventive treatment approaches may have to be developed for patients in CKD stages 3-5 to halt progression of CKD-MBD. 1. Introduction Availability of phosphate is of key importance for a number of normal physiological body functions including bone de- velopment, cellular membrane integrity (phospholipid con- tent), and energy transfer (mitochondrial metabolism). Normal phosphate homeostasis, thus, maintains serum con- centrations quite constantly between 0.8 and 1.45 mmol/L in the normal population. In this line, meals containing a high phosphate load in most instances do not acutely raise the serum phosphate levels, because phosphaturia may become augmented by as yet undeﬁned mechanisms [1]. Further- more, serum phosphate levels show rather a circadian rhythm which does not parallel intake (phosphate peaks in the early morning hours) [2]. In health, the kidney excretes approximately two thirds of the daily dietary phosphate load, and even with deteriorating kidney function in CKD, this excretion rate remains relatively well maintained [3]. Acute “unphysiological” oral phosphate intake is probably managed by the so-called phosphatonins or by adaptations of the ﬁltered load [3, 4]. It appears that the body activates a number of potent systems in order to avoid both the occurrence of hyperphosphatemia. 2. Epidemiology of Hyperphosphatemia in CKD Patients Kestenbaum and colleagues were the ﬁrst to publish data from a large observational study studying the relationship between phosphate serum levels and outcomes in a CKD cohort [5]. More than 6,000 CKD patients were cross- sectionally available for analysis, while 3,490 of them had a serum phosphate measurement during the previous eighteen months. The major result was that phosphate serum levels were found to be in the normal range until a GFR of 30 mL/min was reached; only from then on average phos- phate levels started to rise beyond the upper normal range and started to become inversely related to GFR, while it is yet unclear when serum phosphate levels tend to rise “within” the normal range in CKD [6]. In Kestenbaum’s study, serum phosphate levels above 3.5 mg/dL were already