Evaluation of calcium acetate/magnesium carbonate as a phosphate binder compared with sevelamer hydrochloride in haemodialysis patients: a controlled randomized study (CALMAG study) assessing efficacy and tolerability.

BACKGROUND: Phosphate binders are required to control serum phosphorus in dialysis patients. A phosphate binder combining calcium and magnesium offers an interesting therapeutic option. METHODS: This controlled randomized, investigator-masked, multicentre trial investigated the effect of calcium acetate/magnesium carbonate (CaMg) on serum phosphorus levels compared with sevelamer hydrochloride (HCl). The study aim was to show non-inferiority of CaMg in lowering serum phosphorus levels into Kidney Disease Outcome Quality Initiative (K/DOQI) target level range after 24 weeks. Three hundred and twenty-six patients from five European countries were included. After a phosphate binder washout period, 255 patients were randomized in a 1:1 fashion. Two hundred and four patients completed the study per protocol (CaMg, N = 105; dropouts N = 18; sevelamer-HCl, N = 99; dropouts N = 34). Patient baseline characteristics were similar in both groups. RESULTS: Serum phosphorus levels had decreased significantly with both drugs at week 25, and the study hypothesis of CaMg not being inferior to sevelamer-HCl was confirmed. The area under the curve for serum phosphorus (P = 0.0042) and the number of visits above K/DOQI (≤1.78 mmol/L, P = 0.0198) and Kidney disease: Improving global outcomes (KDIGO) targets (≤1.45 mmol/L, P = 0.0067) were significantly lower with CaMg. Ionized serum calcium did not differ between groups; total serum calcium increased in the CaMg group (treatment difference 0.0477 mmol/L; P = 0.0032) but was not associated with a higher risk of hypercalcaemia. An asymptomatic increase in serum magnesium occurred in CaMg-treated patients (treatment difference 0.2597 mmol/L, P < 0.0001). There was no difference in the number of patients with adverse events. CONCLUSION: CaMg was non-inferior to the comparator at controlling serum phosphorus levels at Week 25. There was no change in ionized calcium; there was minimal increase in total serum calcium and a small increase in serum magnesium. It had a good tolerability profile and thus may represent an effective treatment of hyperphosphataemia.

Complement factor H gene polymorphism and risk of cardiovascular disease in end-stage renal disease patients.

The main cause of increased mortality in end-stage renal disease (ESRD) is cardiovascular disease (CVD). Complement factor H (CFH) may affect risk of CVD. Our study investigates a role of CFH Y402H polymorphism as a potential risk factor of CVD in a large group of patients. A group of 1200 patients with ESRD and 818 healthy controls were genotyped for the Y402H (T1277C) polymorphism. There was a significant difference in genotype frequencies between patients with CVD and those without CVD and healthy controls (p<0.001). Homozygosity for the C allele in CVD patients was associated with an odds ratio of 7.28 (95 % CI 5.32-9.95). No significant difference was found between patients without CVD and controls. Multivariate logistic regression analysis showed that Y402H genotype was independently associated with cardiovascular comorbidity in ESRD patients. This is the first study suggesting an association between CFH gene polymorphism and susceptibility to CVD in dialyzed patients.