NDT Advance Access originally published online on June 13, 2008
Nephrology Dialysis Transplantation 2008 23(8):2709-2710; doi:10.1093/ndt/gfn344
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Reply to Dr S.C. Palmer and co-workers
E-mail: olgaard{at}rh.dkWe thank Dr Palmer and co-workers for their careful response to our Editorial Comments in the June issue of NDT [1] to their meta-analysis: ‘Vitamin D Compounds in Chronic Kidney Disease,’ published in Ann Intern Med 2007 [2].
- We certainly do agree with Dr Palmer's last remark in the reply on the need for further large-scale research on mineral and bone disorders in CKD, as also clearly stated in our Editorial Comments [1].
- It now appears in their reply that some of the rather strong conclusions in their meta-analysis, which we opposed, are modified and less strongly promoted.
- Both Dr Palmer and Dr M. Tonelli refer in their reply to our Editorial Comment to situations, where therapeutic replacement may be harmful and they both mention ‘e.g. oestrogen plus progestin after menopause.’ We do agree with that, but it is, however, not the correct clinical situation to use for comparison with vitamin D deficiency in uraemic patients, as neither calcitriol nor EPO replacement therapy of uraemic patients should be compared to pharmacological hormone replacement therapy for post-menopausal women. Vitamin D deficiency should rather be compared with hormone substitution therapy of ovariectomized young women.
- As pointed out in our editorial, Dr Palmer et al. correctly mentioned in their meta-analysis a number of limitations to their study [2]. In spite of this, and in spite of the fact that none of the studies in the meta-analysis were either powered or designed to evaluate clinically relevant outcomes, such as mortality, Dr Palmer et al. continued to draw some rather powerful conclusions. In our opinion, their conclusions should have been much more moderate or maybe the authors should even have considered, whether the data in their meta-analysis were of too poor quality to warrant publication. It could instead have been turned into a Letter to the Editor and/or to the authorities stressing the need for good RCTs in this scientific field.
We thank Dr Tonelli for his response to our critical editorial Comments [1] to his editorial on: ‘Vitamin D in patients with CKD: nothing new under the sun,’ published in Ann Intern Med, 2007 [3]. We do have some comments to Dr Tonelli's response, which was published together with our Editorial Comments [1] in the June issue of NDT:
- Unfortunately, and strangely, there is a world in between what Dr M. Tonelli and we consider as good scientific quality. From Dr Tonelli's reply, it is clear that he only finds that scientific evidence exists, if proven by randomized controlled trials (RCTs), optimally supported by meta-analyses, while we also do accept the results of good clinical investigations and of well-performed experimental studies. Without such studies no ideas would be created that later could form the basis for subsequent RCTs. As such, we do accept the importance of RCTs and meta-analyses, but do not accept that ‘very little evidence exists to support or advocate for such unproven therapies in the absence of good quality evidence,’ [3] when dealing with the topic of vitamin D.
- As mentioned above to Dr Palmer, neither calcitriol nor EPO therapy of uraemic patients should be compared with pharmacological hormone replacement therapy for post-menopausal women, but vitamin D deficiency should rather be compared with hormone substitution therapy of ovariectomized young women. We agree with Dr Tonelli that physiology and pathophysiology are difficult issues to perceive.
- Of course it is not the call for RCTs that is characterized as ‘potentially dangerous’; we do agree with the need for more RTCs, as concluded in our editorial, but as also stated in our editorial [1], we strongly disagree with Dr Tonelli's statement: ‘In the meantime, it is hard to argue strongly for the use of vitamin D in patients receiving dialysis’ [3], which means that until RCTs and meta-analyses are created, we should withhold vitamin D therapy from dialysis patients, a situation that would last for years.
- We also strongly disagree with the design of future RCTs, which was suggested by Dr M. Tonelli in his editorial [3], where he stated that ‘the most useful way to start would be a trial comparing injectable paracalcitol with placebo in patients receiving dialysis.’ Such an industry-like type of design (why paracalcitol ? and not the genuine hormone, calcitriol ?) would for years leave a population of uraemic patients untreated with severe hyperparathyroidism and renal osteodystrophy (the placebo group) in an effort to examine for hard endpoints, such as mortality.
Conflict of interest statement. None declared.
1 Nephrological Department P Rigshospitalet and 2 Nephrological Department B Herlev Hospital, Copenhagen, Denmark
References
- Olgaard K, Lewin E. Use (or misuse) of vitamin D treatment in CKD and dialysis patients: a recent meta-analysis on vitamin D compounds in chronic kidney disease [1] and an editorial comment [2] accompanying this meta-analysis have already been published. We believe that these papers deserve some comments in the interest of the NDT readership. Nephrol Dial Transplant (2008) 23:1786–1789.
[Free Full Text] - Palmer SC, McGregor DO, Macaskill P, et al. Meta-analysis: vitamin D compounds in chronic kidney disease. Ann Intern Med (2007) 147:840–853.
[Abstract/Free Full Text] - Tonelli M. Vitamin D in patients with chronic kidney disease: nothing new under the sun. Ann Intern Med (2007) 147:880–881.
[Free Full Text]
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