The Authors Reply:

Abstract

Yokoyama et al.1.Yokoyama K. Yoshida H. Maruyama Y. et al.Should the targeted value of the phosphate be reviewed lower to normal range from the viewpoint of vascular calcification?.Kidney Int. 2010; 77: 928Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar take issue with our recommendation to lower elevated phosphorus levels toward the normal range in patients with chronic kidney disease (CKD) stage 5D (2C), as reported in the KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guidelines for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), chapter 4.1.1.2.Kidney Disease-Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).Kidney Int Suppl. 2009; 76: S1-S130Google Scholar The strength of this recommendation has been classified as ‘2’, meaning that the majority of people in this situation would want the recommended course of action, but many would not, and different choices will be appropriate for different patients. The quality of the studies used for this recommendation was classified as ‘C’, indicating that it was low. This means that the true effect may be substantially different from the estimate of the effect. The authors mention that many studies have shown a close association between serum phosphorus concentration and the relative risk of mortality. Based on these observations, and their data demonstrating an association of vascular calcification with serum phosphorus concentrations of 4.8 mg/dl or greater, they claim that the serum phosphorus levels should be normalized in patients with CKD stage 5D. As pointed out in our CKD-MBD guideline, it is impossible to draw firm conclusions from association studies, because they are only hypothesis generating. There are several examples in recent literature wherein randomized controlled trials did not confirm the results of observational studies in patients with CKD, as for example with anemia correction or cholesterol lowering.3.O’Shaughnessy D.V. Elder G.J. Review article: patient-level outcomes: the missing link.Nephrology (Carlton). 2009; 14: 443-451Crossref PubMed Scopus (9) Google Scholar It is also not clear whether slowing vascular calcification translates into improvements in clinical outcomes, and therefore this should be considered as a surrogate end point only and should not supersede conclusions from associative mortality studies. To date, there is no convincing report showing that the active normalization of hyperphosphatemia with any therapy (phosphate binders, diet, or dialysis) improves hard patient outcomes such as fractures, cardiovascular events or death. Thus, although the experimental evidence that phosphorus is a uremic toxin is strong,4.Barreto F.C. Barreto D.V. Liabeuf S. Drueke T.B. et al.Effects of uremic toxins on vascular and bone remodeling.Semin Dial. 2009; 22: 433-437Crossref PubMed Scopus (16) Google Scholar definitive human data are lacking. Therefore, although it is reasonable to lower serum phosphorus levels towards normal, caregivers must weigh any potential benefit against the potential adverse consequences of such an approach for a given patient.5.Fadem S.Z. Moe S.M. Management of chronic kidney disease mineral-bone disorder.Adv Chronic Kidney Dis. 2007; 14: 44-53Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar