Blog entry by Arif Khwaja
An interesting pilot study is published in this months cJASN adds more data to the never ending debate about the benefits of calcium binders versus non calcium based binders. A multicentre RCT based in Napoli, Italy assigned 212 CKD3/4 patients to sevelamer or calcium carbonate. The primary endpoint was all cause mortality and 22/105 patients died in the calcium carbonate arm compared to 12/107 in the sevelamer arm (p<0.05) over 3 years follow up. The time to dialysis inception was longer in the sevelamer arm though the criteria for starting dialysis were not standardised. One of the criticisms of the DCOR study ( a huge RCT which failed to show any difference in outcomes between sevelamer and caclcium binders in a prevalent dialysis population) was that by the time dialysis starts all the vascular calcification has taken place - therefore the authors are to be commended for doing an RCT in the predialysis population. Furthermore the de novo onset of coronary artery calcification was 81.8% in the calcium group versus 12.8% in the sevelamer group.
However there are a numbers of issues to bear in mind:
i) the study wasnt blinded - not clear why not
ii) there was not target phosphate to achieve - clinicians just had to maintain phosphate concentration between 2.7-4.6mg/dl
iii) the problem with this approach is that the final and time-average phosphate concentration was significantly lower in the sevelamer group than the calcium group! Thus its impossible to know whether the improvement in mortality is due to better phosphate control or use of a non-phosphate binder..... in fact in adjusted models for baseline and time-varying covariates the protective effect of sevelamer was lost!
iv) to my mind the most interesting part of the study is the that its the first RCT to suggest that lowering phosphate in the predialysis population may improve outcomes.
v) this study reinforces the need for an RCT in the predialysis population to address 2 specific issues - what the optimal phosphate level is (if any) and whether using a calcium vs non-calcium binder makes a difference. To be fair to the authors they acknowledge that this is a pilot study and recognise the need for a large RCT
vi) Whilst in my opinion the cost of sevelamer doesn't justify its widespread use in the predialysis population once the drug becomes generic and prices fall it would be reasonable to use sevelamer as an alternative to calcium based binders.