Early initiation of dialysis fails to prolong survival in patients with end-stage renal failure

Sir,

We write to express our concern about a letter recently published in NDT by Van Biesen et al. [1]. In this letter regarding initiation of dialysis, attention was drawn to our recent paper on this subject [2]. In our study, we concluded that starting dialysis for end-stage renal failure based on patients’ symptoms rather than level of renal function did not disadvantage these patients in terms of survival. Van Biesen et al. made two specific points in their letter that we take issue with.

The first point concerns patient deaths before reaching dialysis. We identified 22 patients who had been accepted for dialysis but who died before actually starting dialysis. In their letter, van Biesen et al. claim that adding these 22 patients to the late start group leads to a significant survival benefit for the early start group of patients. They attempt to support this assertion using a chi-square test on our data. However, the chi-square test is not an acceptable method for assessing survival when used in isolation. The only role that the chi-square test has in survival analysis is as one of several steps in performing the Mantel–Haenszel test (also known as the log-rank test) [3]. We used an appropriate method, Kaplan–Meier survival analysis, with these 22 patients added to the late start group and found no survival difference with a log-rank P-value of 0.71. Details of this analysis are provided in the original article.

The second point made by Van Biesen et al. was of concern that of 2095 patients with an estimated creatinine clearance (ECC) below 20 ml/min that were identified in our study, only 933 patients started dialysis. We gave a complete description of the methods used to identify patients in our original article but are pleased to provide further details. The 1162 patients who had an ECC of <20 ml/min but were not included in further analysis consisted of patients with acute renal failure and patients with chronic renal failure who had not yet started dialysis. Of these 1162 patients, 361 patients had acute renal failure and are not relevant to our analysis, 216 patients continue to attend our clinics, have died or have started dialysis since the study was reported. 191 patients have been discharged from our care, 373 patients have died and only 21 patients are not being followed up in our centre.

One of the main aims of our study was to remove the effect of late referral. Of those 373 patients who had died without ever having dialysis, 157 patients met our inclusion criteria of being referred more than 180 days prior to endpoint, had enough data to remove lead-time bias and had either been accepted for dialysis or no decision regarding this had been made. The rest of the 373 patients either were referred late, did not have an early enough ECC to remove lead-time bias or had been turned down for dialysis. The 157 patients who did meet our inclusion criteria included the 22 patients who have already been included in our analysis as discussed above.

This group of 157 patients displayed a wide range of ECC prior to death with a median ECC prior to death of 16.4 ml/min (inter-quartile range 11.7, 20.3). Only 16 patients had an ECC of <8.3 ml/min prior to death; 8.3 ml/min was the median ECC in our study group and was used to separate early start patients from late start patients. Six of these patients had been accepted for dialysis and were part of the 22 patients discussed above and described in our original paper. Of the remaining 10 patients, it was not possible to ascertain whether or not these patients should have been started on dialysis or whether this was deemed inappropriate. However, in view of the possible assertion that these patients might have survived had they started dialysis sooner, we have added these 10 patients to the late start group as well as the 22 patients already mentioned. Despite this there is still no survival benefit on Kaplan–Meier analysis (log-rank P = 0.90).

In summary, we are concerned about the conclusions that Van Biesen et al. have drawn from our study. It is clear from their description of our late start group as a ‘too late’ start group that Van Biesen et al. are themselves biased towards early initiation of dialysis. Our results support the predominantly symptom-based dialysis initiation policy practised by many units which we feel should continue unless evidence is produced to support any other policy. Other recent studies support this view [46]. The issue of when to start dialysis still requires a prospective randomized trial and we await the findings of the ongoing IDEAL study in Australia/New Zealand [7] with interest.

Conflict of interest statement. None declared.

Jamie P. Traynor1,2, Keith Simpson1, Colin C. Geddes2, Christopher J. Deighan1 and Jonathan G. Fox1

1Glasgow Royal Infirmary Renal Unit 2Western Infirmary Renal Unit Glasgow, UK Email: jamie.traynor1{at}ntlworld.com

References

  1. Lameire N, Vanholder R, Van Biesen W. Reply. Nephrol Dial Transplant 2003; 18: 1229[Free Full Text]
  2. Traynor JP, Simpson K, Geddes CC, Deighan CJ, Fox JG. Early initiation of dialysis fails to prolong survival in patients with end-stage renal failure. J Am Soc Nephrol 2002; 13: 2125–2132[Abstract/Free Full Text]
  3. Brown RA, Swanson Beck J. Medical Statistics on Personal Computers, 2nd Edn. BMJ Publishing Group, 1994; 109–114
  4. Korevaar JC, Jansen MA, Dekker FW et al. When to initiate dialysis: effect of proposed US guidelines on survival. Lancet 2001; 358: 1046–1050[CrossRef][ISI][Medline]
  5. Fink JC, Burdick RA, Kurth SJ et al. Significance of serum creatinine values in new end-stage renal disease patients. Am J Kidney Dis 1999; 34: 694–701[ISI][Medline]
  6. Beddhu S, Samore MH, Roberts MS et al. Impact of timing of initiation of dialysis on mortality. J Am Soc Nephrol 2003; 14: 2305–2312[Abstract/Free Full Text]
  7. Pollock C, Collins J, Harris D. IDEAL Study—Initiating Dialysis Early and Late. http://www.nephrology.edu.au/trials/index.htm. 2003.




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