Phosphate binders: Sevelamer in the prevention and treatment of hyperphosphataemia in chronic renal failure

摘要

In chronic kidney disease patients, bone and mineral abnormalities have a major impact on morbidity and mortality. Hyperphosphatemia has been associated with increased mortality and with the development of cardiovascular calcification, an independent predictor of mortality. Sevelamer, or more precisely 'sevelamer hydrochloride', is a weakly basic anion-exchange resin in the chloride form that was introduced in 1997 for the treatment of the hyperphosphataemia of patients with end-stage renal failure. Sevelamer sequesters phosphate within the gastrointestinal tract, so prevents its absorption and enhances its faecal excretion. Over the succeeding years, large numbers of patients have been treated with sevelamer, and it has fulfilled expectations in helping to control the hyperphosphataemia of end-stage renal failure. Additionally treatment with sevelamer was accompanied with lower incidence of hypercalcemia, decreased incidence of low PTH levels, a 15-31% decrease of LDL-cholesterol both in dialysis and predialysis patients, decreased C-reactive protein, amelioration of hyperuricemia and low fetuin A, decrease of uremic toxins, suggesting an overall anti-inflammatory effect. In incident dialysis patients, treatment with sevelamer has been associated with better survival, while in prevalent patients a clear benefit could only be demonstrated in older patients and in patients treated for more than 2 years. In dialysis patients, the treatment of hyperphospathemia with calcium based compounds, when compared with sevelamer, is associated with more frequent episodes of hypercalcemia, suppression of intact PTH and with progression of coronary calcifications. In the presence of adynamic bone disease, calcium load has a significantly higher impact on aortic calcifications and stiffening. Sevelamer treatment resulted in no statistically significant changes in bone turnover or mineralization compared with calcium carbonate, but bone formation rate increased and trabecular architecture improved only with sevelamer. In conclusion, the treatment of hyperphosphatemia with sevelamer hydrochloride, a noncalcium and non-metal containing phosphate binder, is associated with a beneficial effect on vascular calcification progression, bone disease and most likely with a survival benefit in some hemodialysis patients populations. Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphataemia in CKD patients. Sevelamer carbonate formulated as a powder for oral suspension presents a novel, patient- friendly alternative to tablet phosphate binders. Safety and efficacy of sevelamer carbonate powder compared with sevelamer hydrochloride tablets in CKD patients are equivalent, with Sevelamer carbonate having fewer side effects from gastrointestinal tract.