Second Chances in Mineral Metabolism

The optimal management of disordered mineral metabolism in patients with chronic kidney disease has been among the most controversial topics in clinical nephrology during the past decade. The origins of the current controversies can be traced back to the initial reports from large-scale human studies of important associations between individual mineral metabolites—calcium, phosphorus, parathyroid hormone (PTH)—and adverse clinical outcomes (1,2). The volume of the mineral metabolism discourse escalated with the publication of complex pharmacoepidemiologic studies that suggested that therapy with active forms of vitamin D might improve survival (3,4). In the next wave of individual analyte studies that followed, deficiencies in the vitamin D axis were found to be associated with increased risk of cardiovascular disease and death (5,6). The introduction of cinacalcet into clinical practice doubled the number of available PTH-lowering therapies but, predictably, launched a new layer of jostling to identify the ideal therapeutic cocktail for dialysis patients. Unfortunately, it is doubtful that clear answers will ever emerge if we continue to assume that “better control” of individual mineral metabolism analytes, as judged by national and international practice guidelines, will translate into improved patient survival rather than directly comparing survival rates of different strategies in head-to-head studies.How to best treat dialysis patients' elevated serum phosphate levels is a related quagmire. Again, limited definitive data have promoted a dependence on nonvalidated surrogate markers and expert opinion (educated guessing), which has sparked seemingly never-ending controversy, including calcium versus noncalcium-based binders, metal versus polymer, efficacy versus safety, and so on. These issues have deflected attention from the most fundamental questions for which we also have no answers: Will reducing an elevated serum phosphate level improve survival and, if so, what is the optimal level to target? The imminent bundling of dialysis-related medications into a …