A calcium-free treatment designed to cut death rates in dialysis patients is no better than standard medication, according to a major study.
Genzyme Corp says that Renagel (sevelamer HCl) represents a major breakthrough in the care of kidney patients because by binding phosphate without using calcium the treatment should in theory cut cardiovascular risk and reduce mortality rates.
This hope appeared to be borne out, when in January this year a small study, sponsored by Genzyme, suggested that deaths rates were lower in patients on Renagel compared to those on older treatments. The Renagel in New Dialysis study was a randomised open-label trial involving 127 patients new to hemodialysis at five dialysis centres across the USA. However, a much larger study also published in the Nature journal Kidney International suggests the optimism was premature.
The Dialysis Clinical Outcomes Revisited (DCOR) trial of 1,068 patients found that Renagel did not reduce all-cause mortality in dialysis patients as compared with calcium-based phosphate binders. Wadi Suki of the Baylor College of Medicine, in Houston, Texas, who led the new study, said the results indicated that cutting death rates in end-stage kidney patients was a "daunting task". Renagel did appear to have an effect on mortality in prevalent dialysis patients aged 65 years and older but this was not due to fewer cardiovascular events.
Dr Suki said the different outcomes of the two studies might be at least in part, due to their different designs and he noted that in the earlier, smaller study, patients were followed for a longer period. He added: "In general, future studies in dialysis patients should be large, of long duration, and possibly enroll patients enriched for higher event rates."
Kidney specialists are anxious to make inroads into the very high death rates in patients with advanced disease, and in the USA, the annual all-cause mortality rate of dialysis patients is nearly 25%. Phosphorus retention is a major contributing factor to mortality in dialysis patients, yet the calcium-based phosphate binders used to prevent this could contribute to arterial calcification, which is associated with arterial stiffening and increased mortality.
Renagel had been hailed as the solution to the calcium-based phosphate binder dilemma and the drug netted $135.1 million for Genzyme in the last quarter of 2006, a rise of 22%. In the USA alone, there are around 350,000 people on dialysis, and the numbers are increasing by almost 8% annually. By Michael Day