Peripheral vascular disease and serum phosphorus in hemodialysis: A nested case-control study

Background: Serum phosphorus (P) and the product of serum calcium × serum P (Ca × P), are frequently elevated in end-stage renal disease patients on maintenance hemodialysis (HD). Elevated P and Ca × P have been associated with vascular calcification in dialysis patients. Objective: To examine the role of P and Ca × P as risk factors for incident peripheral vascular disease (PVD) in HD patients with pre-existing CVD. Methods: This nested case-control study is drawn from the 11 incident PVD events reported in the cohort of the Secondary prevention with antioxidants of cardiovascular disease in end-stage renal disease (SPACE): a randomized placebo-controlled trial. PVD was defined clinically and confirmed ultrasonographically. Each individual with a PVD event was matched for SPACE treatment group (vitamin E or placebo), age (in 4-year categories) and gender with two individuals who had no CVD end point during the follow-up period. Results: Serum P and Ca × P levels were significantly higher in PVD patients than in controls. In univariate logistic regression analysis, only serum P predicted PVD in this population (OR 2.02, 95% CI 1.07-3.81, p=0.03). In multivariate analysis, adjustment was made for variables dissimilar by PVD status including underlying renal disease, diabetes, smoking, history of angina pectoris, prescription for vitamin D₃, erythropoietin, calcium channel blockers and aspirin. In this model, serum P remained the only significant predictor of incident PVD (OR 2.4, 95% CI 1.01-5.74, p=0.04). Conclusions: Findings of the present study are consistent with a role for serum P and Ca × P in the pathogenesis of PVD in HD patients.