Progression of coronary artery calcification in patients with chronic kidney disease. Role of phosphorus binders

Introduction and Aims: Coronary artery calcifications (CAC) are more frequent in patients on dialysis (ESRD-patients) than in general population and rapidly proceed. Progression may cause further cardiovascular events. Greater prevalence and progression of CAC have been ascribed to exoge- nous calcium load consequent to high-calcium dialysate, and/or calcium containing phosphate binders (CCPB). Prevalence and progression of CAC have been recently reported to be greater in pre-dialysis patients than in normal subjects; progression was found to be correlated to phosphorus despite the majority of patients had normal concentration; fatal and not-fatal cardiovascular events occurred with manifest progression of CAC. In ESRD-patients progression of CAC can be halted by a non-calcium containing phosphate binder (sevelamer, S) but not CCPB. The present study was performed to assess the role of CCPB and S on the progression of CAC in patients with CKD not on dialysis (CKD-patients). Methods: Consecutive out-patients (stage 3-4 CKD), homogeneous for age, biochemical variables and baseline TCS (mean TCS:320-470 Agatston Units) were randomized to receive S (1600 mg/day) or CCPB (calcium carbonate, 2 gr/day) throughout the study (18 months). In prior study these doses did not cause suppression of PTH and/or hypercalcemia. Treated patients exhibiting hypercalcemia or suppression of PTH exit the study. Agents affecting mineral metabolism were not allowed. Serum calcium phosphorus, i-PTH, homocysteine, C-reactive protein, triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol were measured every 3 months. Progression of CAC was assessed measuring total calcium score (TCS) by computed tomography. Scans were obtained at start (initial) and end of observation period (final). Data of patients treated with CCPB and S were compared with those of non-treated CKD-patients (Controls; C). Results: Seventy-six patients were enrolled in three groups: C=n.27; CCPB=n.22; S=n.27. Initial and final biochemical variables were unchanged but final TCS was significantly increased in three groups. TCS proceeded by 56% and 55% in patients treated with C and CCPB, respectively; and by 21% in those treated with S. Mean TCS and annualized progression were not different between patients treated with CCPB and C. No episodes of hypercalcemia were encountered. PTH remained unchanged. Patients free from CAC at the start remained non calcified at the end of the study. Conclusions: Progression of CAC is rapid in CKD-patients despite baseline normality of mineral metabolism parameters and not exogenous calcium load. Progression was greater in patients treated with CCPB and C but small in those treated with S. Study design and small number of patients did not allow to determine in which manner S contributed to the benefit on CAC progression. When prescription and reimbursement problem will be overcame, larger studies are mandatory to better establish the efficacy of S in reducing CAC progression and eventually morbidity and mortality in CKD-patients.