From Phosphaturia to Cardiovascular Protection

Mortality among patients on maintenance hemodialysis is excessive with an annualized mortality rate of 20% among U.S. patients. Moreover, cardiovascular disease is the leading cause of morbidity and mortality among this population. The phenotype of the patient on maintenance hemodialysis is extremely complex and indeed this patient population is well known to have a high prevalence of multiple traditional (e.g. hypertension and diabetes) and non-traditional cardiovascular (e.g., anemia, vascular calcification, etc) that contribute to excessive cardiovascular morbidity and mortality. Studies in animal models and humans have clearly demonstrated that derangements in hormonal regulators of mineral metabolism are associated with cardiovascular disease including vascular calcification and left ventricular hypertrophy, common complications of end-stage kidney disease. Dissecting out the leading target for intervention within the complex pathophysiology and hormonal milieu of the uremic environment in people on dialysis has been a vexing and difficult problem. Hence, over the past two decades large-scale randomized controlled trials aimed at dose of dialysis 1 , dialysis membrane type 2 , statins 3, 4 , secondary hyperparathyroidism and vascular calcification 5, 6 , and anemia 7, 8 have failed to demonstrate improvement in clinical outcomes. Alas, worldwide no new therapies have been definitively shown to reduce morbidity and mortality in hemodialysis populations. Recently, the search for new targets has focused on the ever increasingly complex mineral metabolism milieu in uremic patients on hemodialysis. 9