With great interest, we have read the comments of Traynor et al. on our reply regarding the NECOSAD study, in a recent issue of NDT.
We agree completely with the new interpretation they give here to their study results: that starting dialysis purely on numbers is probably not a good policy, and that clinical symptoms are a better basis to start dialysis, a conclusion that was also supported by the NECOSAD data and is also supported by a more recent study by Beddhu et al. [1], and was already stated in our previous comment. This conclusion as the authors formulate it now is, however, slightly different from the one given in the original publication of Traynor et al., where it was stated that Until evidence becomes available from a prospective randomized trial that eliminates the effect of lead time bias, early initiation of dialysis cannot be supported, which is a far more negative interpretation, and might erronously lead to the conclusion that the later dialysis is started, the better the outcome.
We also agree that a simple chi-square test is not an ideal method for comparing survival in groups, but as we did not have the original data at our disposal, it was the only way for us to calculate the statistics. In addition, it was not really the numbers that mattered to us, it was more the concept of inverse lead time bias that we wanted to stress. It is indeed very conceivable that patients can drop out of the study because they died before they were able to start dialysis. In this regard, the criteria on which it was decided whether a patient was acceptable for dialysis are of course of importance. Traynor et al. consider for their calculations only patients who were considered for dialysis and skipped the others. This might lead to selection bias in favour of the fittest patients (and thus in favour of no difference), if the reasons why patients were not considered anymore for dialysis were related to their late initiation of renal replacement therapy (RRT). At the least, this selection makes the study results hard to generalize for countries like Belgium, where all patients have a trial of RRT.
We do not agree that we should be biased towards early start of RRT. We just want to avoid the perception that the start of RRT should be delayed as long as possible should become generalized. As we read the comments of Traynor et al., we believe that the authors also agree that a timely start of dialysis, i.e. at the moment the patient becomes symptomatic irrespective of GFR numbers, is probably the best strategy.
In addition, we agree with the authors that only a prospective randomized trial will be able to provide us with the correct answer. Only in this way, will the problem of lead time bias and selection bias can be correctly avoided. In addition, GFRs can be measured in prospective studies instead of calculated, as it is clear that estimated creatinine clearances can lead to erroneous conclusions, as patients with low serum creatinines because of malnutrition, or poor general condition will by these methods be categorized in the early start group, a result that was also confirmed in the study by Beddhu et al. However, even in such a prospective trial, scrutinous notification of the clinical status of the patient will be necessary, as we still believe that this will, even in a prospective trial, be more important as a predictor of outcome than merely a number of GFR.
Conflict of interest statement. None declared.
Renal Division University Hospital Ghent Belgium Email: isabel.vandorpe{at}ugent.be
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