Maureen A. Dillon

Cardiac calcification in adult hemodialysis patients: A link between end-stage renal disease and cardiovascular disease?

OBJECTIVES We sought to determine clinical and laboratory correlates of calcification of the coronary arteries (CAs), aorta and mitral and aortic valves in adult subjects with end-stage renal disease (ESRD) receiving hemodialysis. BACKGROUND Vascular calcification is known to be a risk factor for ischemic heart disease in non-uremic individuals. Patients with ESRD experience accelerated vascular calcification, due at least in part to dysregulation of mineral metabolism. Clinical correlates of the extent of calcification in ESRD have not been identified. Moreover, the clinical relevance of calcification as measured by electron-beam tomography (EBT) has not been determined in the ESRD population. METHODS We conducted a cross-sectional analysis of 205 maintenance hemodialysis patients who received baseline EBT for evaluation of vascular and valvular calcification. We compared subjects with and without clinical evidence of atherosclerotic vascular disease and determined correlates of the extent of vascular and valvular calcification using multivariable linear regression and proportional odds logistic regression analyses. RESULTS The median coronary artery calcium score was 595 (interquartile range, 76 to 1,600), values consistent with a high risk of obstructive coronary artery disease in the general population. The CA calcium scores were directly related to the prevalence of myocardial infarction (p < 0.0001) and angina (p < 0.0001), and the aortic calcium scores were directly related to the prevalence of claudication (p = 0.001) and aortic aneurysm (p = 0.02). The extent of coronary calcification was more pronounced with older age, male gender, white race, diabetes, longer dialysis vintage and higher serum concentrations of calcium and phosphorus. Total cholesterol (and high-density lipoprotein and low-density lipoprotein subfractions), triglycerides, hemoglobin and albumin were not significantly related to the extent of CA calcification. Only dialysis vintage was significantly associated with the prevalence of valvular calcification. CONCLUSIONS Coronary artery calcification is common, severe and significantly associated with ischemic cardiovascular disease in adult ESRD patients. The dysregulation of mineral metabolism in ESRD may influence vascular calcification risk.

A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients

Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia and aluminum-based binders that result in total body aluminum accumulation over time. This investigation describes the use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis patients and compares it with a standard calcium-based phosphate binder. An open-label, randomized, crossover study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder washout period, stable hemodialysis patients were administered either sevelamer or calcium acetate, and the dosages were titrated upward to achieve improved phosphate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Eighty-four patients from eight centers participated in the study. There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-2.0 +/- 2.3 mg/dL) and calcium acetate (-2.1 +/- 1.9 mg/dL). Twenty-two percent of patients developed a serum calcium greater than 11.0 mg/dL while receiving calcium acetate, versus 5% of patients receiving sevelamer (P < 0.01). The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 24% mean decrease in serum low-density lipoprotein cholesterol levels. Sevelamer was effective in controlling hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium acetate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients, and its usage may be advantageous in the treatment of dialysis patients.

A randomized, double-blind, crossover design study of sevelamer hydrochloride and sevelamer carbonate in patients on hemodialysis.

AIMS Sevelamer carbonate is an anion exchange resin with the same polymeric structure as sevelamer hydrochloride in which carbonate replaces chloride as the anion. The study investigated the effects of sevelamer carbonate and sevelamer hydrochloride on serum phosphorus, lipids and bicarbonate levels in hemodialysis patients. MATERIALS AND METHODS This was a double-blind, randomized, crossover study. 79 hemodialysis patients were randomly assigned to either sevelamer carbonate or sevelamer hydrochloride for 8 weeks followed by a crossover to the other regimen for an additional 8 weeks of treatment. RESULTS The mean serum phosphorus was 4.6+/-0.9 and 4.7+/-0.9 mg/dl during sevelamer carbonate and sevelamer hydrochloride treatment, respectively. Sevelamer carbonate and sevelamer hydrochloride were equivalent in controlling serum phosphorus, the geometric least square mean ratio was 0.99 (90% CI, 0.95-1.03). Mean total and LDL cholesterol were 144.0+/-33.9 and 59.5+/-24.9 mg/dl, respectively, during sevelamer carbonate treatment and 139.0+/-33.6 and 56.0+/-23.3 mg/dl, respectively, during sevelamer hydrochloride treatment. Serum bicarbonate levels increased by 1.3+/-4.1 mEq/l during sevelamer carbonate treatment. There were fewer gastrointestinal adverse events with sevelamer carbonate. CONCLUSIONS Sevelamer carbonate and sevelamer hydrochloride were equivalent in controlling serum phosphorus and serum bicarbonate levels increased with sevelamer carbonate. Lipid profiles for both were well-below the levels suggested by KDOQI. Sevelamer carbonate may have advantages over sevelamer hydrochloride in the treatment of hyperphosphatemia in hemodialysis patients.