EFFECT OF PHOSPHATE BINDER THERAPY ON MORTALITY IN PRE-DIALYSIS PATIENTS

INTRODUCTION AND AIMS Coronary artery calcifications ( CAC ) are prevalent and severe in all stages of chronic kidney disease. In pre-dialysis patients (NDD-CKD ), CAC display an accelerated progression that is strongly associated to poor outcomes such as cardiovascular events and faster inception to dialysis. Despite the clinical relevance of the latter findings, there is no study aimed at establishing improvement of outcomes by reducing CAC progression in NDD-CKD. The main aim of the present study was to ascertain whether outcomes may be ameliorated by reducing CAC progression in NDD-CKD patients treated with either sevelamer or calcium carbonate. METHODS: This study has been performed in a sub-group of outpatients from a larger multicenter, prospective, randomized study. Inclusion criteria were: age > 18 years, CKD stage 2-4, presence of CAC. Exclusion criteria were: heart failure and/or coronary artery disease, history of myocardial infarction, coronary bypass, angioplasty, stroke, arrhythmia. Patients were treated either with calcium carbonate or sevelamer. Routine blood chemistry was assessed at enrollment and every six months. Clinicians were instructed to control parameters of mineral metabolism according to their everyday practice; targets taken in account were those suggested by K/DOQI guidelines that were available at the start of the study. Recorded events were: sudden death, fatal and not fatal myocardial infarction, other-cause mortality, and inception of dialysis. The scheduled follow-up for evaluation of events was 36-month long. Coronary Calcium Score (CAC-Score) was assessed by computed tomography at study entry, on 6th, 12th, 24th month. Progression of CAC was evaluated as (1) absolute change of CAC-score (change between 24th month and baseline) and (2) annualized progression that take in account the time between scans. Patients were defined progressors when the difference between the last and the baseline CAC-score was ≥ 15%. Data are expressed as mean ± standard deviation. Kaplan-Meier survival curves were created and a long-rank test used for comparisons. Multivariable Cox regression analysis was performed to assess factors significantly associated to events risk. RESULTS: Enrolled patient were n. 113 (n.47 and n. 66 treated with calcium and sevelamer, respectively). Baseline CAC-score was 388±413 and 306±382 AU in calcium and sevelamertreated patients, respectively; p=0.27). CAC-score did not progress in n.1 and in n. 22 patients treated with calcium and sevelamer, respectively; p=0.0001). All survival curves were significantly (p=0.001) worse in calcium-treated patients.