Early Dialysis May Not Improve Survival in Stage V Chronic Kidney Disease

Laurie Barclay, MD

September 18, 2010

August 11, 2010 — Planned early initiation of dialysis in patients with stage V chronic kidney disease is not linked to better survival or clinical outcomes, according to the results of a randomized controlled trial reported in the August 12 issue of the New England Journal of Medicine.

"In clinical practice, there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease, with a worldwide trend toward early initiation," write Bruce A. Cooper, MB, BS, PhD, from Royal North Shore Hospital and Sydney Medical School in Sydney, Australia, and colleagues from the Initiating Dialysis Early and Late (IDEAL) study. "In this study, conducted at 32 centers in Australia and New Zealand, we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease."

Patients at least 18 years old with progressive chronic kidney disease and an estimated glomerular filtration rate (GFR) between 10.0 and 15.0 mL/minute/1.73 m2 of body surface area were randomly assigned to early-start or late-start dialysis. Early start of dialysis was defined as planned initiation when the estimated GFR, calculated with use of the Cockcroft-Gault equation, was 10.0 to 14.0 mL/minute/1.73 m2, and late start was defined as initiation when the estimated GFR was 5.0 to 7.0 mL/minute/1.73 m2. Death from any cause was the main study endpoint.

The study sample consisted of 828 adults randomly assigned between July 2000 and November 2008. Mean age was 60.4 years, there were 542 men and 286 women, and 355 had diabetes.

In the early-start group, median time to the initiation of dialysis was 1.80 months (95% confidence interval [CI], 1.60 - 2.23 months) vs 7.40 months (95% CI, 6.23 - 8.27 months) in the late-start group. Because they became symptomatic, 75.9% of the patients in the late-start group started dialysis when the estimated GFR was above the target of 7.0 mL/minute.

During a median follow-up period of 3.59 years, there were 152 deaths among 404 patients in the early-start group (37.6%) and 155 deaths among 424 patients in the late-start group (36.6%). For early initiation, the hazard ratio of death was 1.04 (95% CI, 0.83 - 1.30; P = .75). Frequency of adverse events, including cardiovascular events, infections, and dialysis complications, also did not differ significantly between the groups.

"In this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes," the study authors write. "The results show that with careful clinical management, dialysis may be delayed until either the GFR drops below 7.0 ml per minute or more traditional clinical indicators for the initiation of dialysis are present."

Limitations of this study include use of an estimated GFR assessment on the basis of the Cockcroft-Gault equation, lack of use of a uniform method of creatinine assessment, and dialysis initiation sooner than indicated by protocol in most patients in the late-start group.

In an accompanying editorial, Norbert Lameire, MD, PhD, and Wim Van Biesen, MD, PhD, from the University Hospital Ghent in Ghent, Belgium, note that the optimal timing for the initiation of dialysis is still debated. They suggest placing in perspective the main conclusion that for asymptomatic patients, renal replacement therapy can be delayed by an average of 6 months.

"In our view, the IDEAL trial supports the currently recommended practice, in which most nephrologists start patients on renal-replacement therapy on the basis of clinical factors rather than numerical criteria such as the estimated GFR alone," Drs. Lameire and Van Biesen write. "Early referral to a nephrologist, a well-organized patient-education program, and careful planning before dialysis is initiated are the cornerstones of such a strategy."

The National Health and Medical Research Council of Australia supported this study, along with the Australian Health Ministers Advisory Council; the Royal Australasian College of Physicians/Australian and New Zealand Society of Nephrology (Don and Lorraine Jacquot Fellowship); the National Heart Foundation (Australia) and the National Heart Foundation (New Zealand); and by unrestricted grants from Baxter Healthcare, Health Funding Authority New Zealand (Te Mana Putea Hauora O Aotearoa), the International Society for Peritoneal Dialysis, Amgen Australia, and Janssen-Cilag.

Some of the study authors have disclosed various financial relationships with Baxter Healthcare, Amgen, Roche, AstraZeneca, Fresenius Medical Care, Shire, and/or Janssen-Cilag.

Disclosure information provided by the editorialists is available here .

New Engl J Med. 2010;363:609-619, 678-680.

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