Phosphate Metabolism Modulation in Chronic Kidney Disease: When, How and to What Extent?

Implication for health policy/practice/research/medical education: The use of calcium containing vs. calcium free phosphate binder is one of the hot topic in Nephrology due to the survival benefit and cost burden associated with the use of the latter. Numerous observations have repeatedly shown that serum phosphorous is associated with poor survival (1). In a large cohort of 1,716 chronic kidney disease (CKD) referred to a Nephrology Center in Emilia Romagna, Italy (2), we investigated the robustness of the association between serum levels of phosphate and the risk of death by any cause or dialysis inception (2). Overall, we analyzed men (66% male) and women of 70 years of age [mean (standard deviation): age 70 (13.6) years] with CKD stage 4 [me-dian estimated glomerular filtration rate (eGFR): 25 mL/ min/1.73m 2 ] (2). Over a relatively short period of time [1.3 (0.9) years] we recorded a total of 451 events (composite endpoint event rate: 202/1000 patient-year) equally distributed between the 2 outcome of interest (i.e. all-cause mortality and dialysis inception) (2). The risk of the composite endpoint was almost linearly and independently associated with serum phosphate levels. In this study co-hort, hyperphosphatemia (serum phosphorous greater than 4.3 mg/dL) was observed in 25% of the study cohort and associated with a significant 104% (hazard ratio: 2.04; 95% Condfidence Interval: 1.44-2.90; P < 0.001) increased risk of either death or dialysis inception (2). Notably, in this study cohort, the risk associated with hyperphos-phatemia was modulated by the presence of diabetes. Indeed, diabetic patients with hyperphosphaemia were at greater risk of unfavorable outcome when compared to non-diabetic patients with hyperphosphatemia (P for interaction test = 0.02) (2). Though numerous studies corroborate these findings, several aspects of phosphorous balance and metabolism still need to be elucidated. What we measure in serum is only a small portion of the total body pool and is tightly regulated by a series of different factors (3). Diet intake, bone metabolism as well as kidney and intestinal excre-tion contribute to determine serum phosphorous levels however mechanism(s) that regulates phosphate excre-tion and exchange among body compartments are far from being elucidated (3). Studies that have investigated when hyperphosphatemia ensues in the course of CKD suggest that this condition may become prevalent when the GFR is reduced below 30 mL/min (i.e. CKD stage 4 according to the National Kidney Founfation classification) (4). However, phosphaturic factors such as fibrobast growth factor 23 (FGF23) …