by Nancy Walsh
Planned early initiation of dialysis in patients with chronic kidney disease did not improve survival or other clinical outcomes, a multicenter randomized trial conducted in Australia and New Zealand found.
The hazard ratio for death among patients who had an early start of dialysis, when the estimated glomerular filtration rate (GFR) was 10 to 14 mL/min, was 1.04 (95% CI 0.83 to 1.30, P=0.75), according to Bruce A. Cooper, MBBS, PhD, of Sydney (Australia) Medical School, and colleagues.
This was in comparison with patients who had a later start, when the estimated GFR was 5 to 7 mL/min, the investigators reported at the European Renal Association-European Dialysis and Transplant Association Congress in Munich. The findings were concurrently published online by the New England Journal of Medicine.
Traditionally, the timing for initiating dialysis was based on the occurrence of signs and symptoms of uremia plus biochemical parameters.
However, based on findings from some observational studies, a worldwide trend has been seen in recent years toward earlier starting, with various national and international guidelines recommending the initiation when the estimated GFR reaches 10 to 15 mL/min/1.73 m2 of body-surface area.
“The GFR targets in these guidelines have clearly influenced the clinical practice of nephrology,” the investigators stated.
For example, the proportion of patients who began dialysis when the GFR was higher than 10 mL/min rose from 19% in 1996 to 45% in 2005.
But more recent data — also observational and therefore potentially subject to bias — have suggested that early-start dialysis may actually be harmful.
To address the questions raised by these contradictory and uncertain findings, Cooper and colleagues conducted the randomized IDEAL (Initiating Dialysis Early and Late) trial at 32 centers.
Between July 2000 and November 2008, 828 adults with stage V kidney disease whose median age was 60.4 years were randomized to early or late start of dialysis, and followed until November 2009.
The study population included almost twice as many men as women, and nearly three-quarters of patients were white.
The primary cause of end-stage renal disease was diabetes in one third of all patients.
The two groups were well matched for baseline characteristics and pharmacologic interventions.
In the early-start group, the median time from randomization to dialysis was 1.80 months (95% CI 1.60 to 2.23), compared with 7.40 months (95% CI 6.23 to 8.27) in the late-start group.
The hazard ratio for initiation of dialysis in the early start group was 2.09 (95% CI 1.81 to 2.41, P<0.001), the investigators reported.
Mean estimated GFR in the early-start group at the time of the initiation of dialysis was 12 mL/min, compared with 9.8 mL/min in the late-start group, for a mean difference of 2.2 mL/min (95% CI 1.8 to 2.6, P<0.001).
During the follow-up period, 152 patients in the early-start group died, as did 155 in the late-start group. There was no difference in survival between the groups.
A sensitivity analysis determined that there also was no significant difference in survival among patients who underwent transplantation, with a hazard ratio for early start of 1.01 (95% CI 0.81 to 1.26, P=0.92).
Nor were there differences in secondary outcomes:
* Cardiovascular events, HR for early start 1.23 (95% CI 0.97 to 1.56, P=0.09)
* Infectious events, HR for early start 0.87 (95% CI 0.70 to 1.08, P=0.20)
* Complications of dialysis, HR for early start 1.08 (95% CI 0.85 to 1.35, P=0.54)
There also were no differences in quality of life, according to the investigators.
“The results [of this study] show that with careful clinical management of chronic kidney disease, dialysis can be delayed for some patients until the GFR drops below 7.0 mL per minute or until more traditional clinical indicators for the initiation of dialysis are present,” they stated.
These findings also highlight the importance of close monitoring of patients with decreasing renal function, and suggest that GFR should not be the sole determinant of the timing of dialysis initiation.
Limitations of the study included its use of an estimated GFR and the lack of a uniform method of creatinine assessment.
Nonetheless, the investigators concluded, “Our results indicate that such trends toward early initiation of dialysis, which have enormous implications in terms of the cost and infrastructure of dialysis services, are unlikely to improve clinical outcomes.”
Nancy Walsh is a MedPage Today contributing writer.