Renal Division, University Hospital Ghent, Belgium Email: wim.vanbiesen{at}rug.ac.be
Sir,
We are pleased with the response of Korevaar et al. [1] to our Editorial Comment on their publication on timing of start of dialysis. The comment confirms that, although evidence in the true scientific sense is still lacking, and different authors apparently defend different recommendations, there is, in fact some form of agreement. The unwritten consensus' seems to be that in patients with low co-morbidity, and with a careful pre-dialysis follow-up by a nephrologist, taking into account all the secondary complications of renal failure, and avoiding malnutrition, the benefit of starting dialysis earlier might be minimal. Therefore, we certainly agree with the recommendation of Korevaar et al. that only the (well-informed) patient and an (unbiased) nephrologist are able to weigh the potential benefits of earlier start of dialysis in this type of uncomplicated end-stage renal disease patients. This viewpoint was reflected in an international opinion survey on timing of start of dialysis [2], where most respondents felt that nutritional status, and appearance of uraemic symptoms should urge the start of dialysis, unless in patients at risk, such as diabetics or patients with uncontrolled hypertension for whom dialysis should be initiated earlier.
However, unfortunately this ideal situation is often lacking.
As already stated in our Editorial Comment, we still believe that there might be some patient selection bias in The Netherlands as compared to other European countries, and especially to the US. Regarding the take-on rate, we point to the following numbers: the Flemish registry reports 140/p.m.p., the same as for Spain and Greece, while the Swedish, the Austrian and the Danish registry report 125/p.m.p.; the Dutch, the Finnish and the Nordic registry report only 90/p.m.p., however. Also for the prevalence, there is a difference, with a reported rate of 800/p.m.p. for Greece and Belgium, 750 for Austria and Sweden, 680 for Denmark, 620 for The Netherlands, and 580 for Finland and Norway. Unless the epidemiology of ESRD is entirely different in the countries with a low take-on rate, these data suggest patient selection, and the probability that a fraction of the potential dialysis population is never submitted to this treatment.
In addition, not only is the take-on rate of importance, but also the age at start (56 years in the NECOSAD cohort vs 65.5 years in the Flemish registry), and the co-morbidity of these patients.
There are other reasons why the NECOSAD population should be considered as a selected cohort. Several studies have demonstrated that >30% of patients starting on dialysis have no pre-dialysis follow-up at all [3]. These patients were excluded in the NECOSAD study, and it is well documented that they are at higher risk of mortality [4]. Furthermore, the NECOSAD reports only on patients who have actually started renal replacement therapy (RRT), and does not take into account those who died before they started dialysis, those who died during the first 3 months of dialysis, or those who were lost to follow-up. This is the opposite of lead-time bias, as the delay of start of RRT might select out the strongest and fittest patients. The study of Traynor et al. [5] points out that this might be the weakest point in the interpretation of this type of retrospective data. In the study of Traynor et al., there was a substantial loss of follow-up of patients, since from >2095 patients who ever had an estimated creatinine clearance below 20 ml/min at some point of time, only 933 patients could be traced to have started RRT. For at least 22 patients, it was demonstrated that they died before they started dialysis, and so these patients should have been attributed to the (too) late start group. If this approach had been implemented, the conclusions from the report of Traynor et al. would have favoured an earlier start of RRT, mortality being higher in the late start group.
In conclusion, the analysis of the NECOSAD cohort indicates that starting patients just because of numbers' is probably not a good strategy. Careful and accurate pre-dialysis follow up is probably as important as the actual timing of start of dialysis, and might be one of the reasons why the observed differences in the NECOSAD cohort are so minimal. Tailoring the start of RRT to the actual needs of the patient, with a careful evaluation of the evolution of co-morbidity, is essential. There is, on the other hand, a lot of indirect evidence that postponing the start of RRT beyond a certain point also has detrimental consequences. In addition, the results of the NECOSAD cohort, and of the report by Traynor et al. can to our opinion not be generalized to the overall population of ESRD patients because both reports are based on a retrospective analysis, be it of a prospectively collected database, and there is no clear reporting of the patients that might have been lost before they had the opportunity to start on dialysis.
Before we can conclude on a general basis that earlier start of dialysis cannot be recommended for the general population, a prospective, randomized trial should be performed. In the meantime, all physicians and health workers involved in the care of (pre-) ESRD patients should realize that high-quality care of future dialysis patients should, in fact, start long before RRT is initiated.
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