Clinical question: Does early initiation of maintenance dialysis for patients with stage 5 chronic kidney disease affect survival?
Background: There is considerable variation in timing of dialysis for patients with chronic kidney disease, with a trend toward early initiation. Observational cohort and case control studies have suggested increased survival and quality of life and decreased complications with early initiation. More recent observational data, however, call this into question.
Study design: Randomized controlled trial.
Setting: Thirty-two centers in Australia and New Zealand.
Synopsis: A total of 828 patients were randomly assigned to the early-start group, in which patients would begin dialysis with an estimated glomerular filtration rate (GFR), using the Cockcroft-Gault Equation, of 10.0 ml to 14.0 ml per minute per 1.72 meters squared, or a late-start group in which dialysis would be initiated at a goal GFR of 5.0 ml/min to 7.0 ml/min.
Though 75.9% of patients in the late-start group initiated dialysis above the target rate due to symptoms or physician recommendation, the mean time to dialysis was still almost six months longer (7.40 months versus 1.80 months).
Patients were followed for a median of 3.59 years. Mortality was similar between the groups: 37.6% and 36.6% of the early-start group and late-start group died, respectively (hazard ratio 1.04, p=0.75). There was no significant difference in other adverse events (cardiovascular events, infections, or complications of dialysis) between the two groups.
The study could not be blinded but the adherence to a definitive endpoint of mortality limits the possibility of observation bias. Post hoc analysis with an alternative method of GFR assessment (the MDRD equation) yielded similar conclusions.
This is the first randomized controlled trial to look at this question, and while concordant with recent observational studies, the conclusions are inconsistent with existing guidelines from national and international groups. Adherence to guidelines recommending early initiation of dialysis is unlikely to improve clinical outcomes while significantly increasing costs.
Bottom line: Early initiation of dialysis is not associated with improved survival in patients with stage 5 chronic kidney disease compared with delaying dialysis to a goal GFR of 7.0 ml/min or the development of symptoms.
Citation: Cooper BA, Branley P, Bulfone L, et al. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med. 2010;363(7):609-619.
Reviewed for TH eWire by Jill Goldenberg, MD, Alan Briones, MD, Chad Craig, MD, Ramiro Jervis, MD, FHM, Brian Markoff, MD, FHM, Andrew Dunn, MD, FACP, FHM, Division of Hospital Medicine, Mount Sinai School of Medicine, New York City.
For more physician reviews of HM-related research, visit our website.