Starting Dialysis Too Early Linked to Increased Mortality Risk

From MedscapeCME Clinical Briefs

Laurie Barclay, MD
Désirée Lie, MD, MSEd

December 7, 2010 — Starting dialysis too early is linked to an increased mortality risk, according to the results of a study reported online December 6 in the Canadian Medical Association Journal.

"Recent studies have reported a trend toward earlier initiation of dialysis (i.e., at higher levels of glomerular filtration rate [GFR]) and an association between early initiation and increased risk of death," write William F. Clark, MD, from the University of Western Ontario, London, Canada, and colleagues. "We examined trends in initiation of hemodialysis within Canada and compared the risk of death between patients with early and late initiation of dialysis."

Using the Canadian Organ Replacement Register from 2001 to 2007, the investigators identified an analytic cohort of 25,910 patients 18 years or older who began hemodialysis. Dialysis was defined as beginning early if the estimated GFR (eGFR) exceeded 10.5 mL/minute/1.73 m2. To compare mortality risk between patients who started dialysis early vs late, the investigators fitted time-dependent proportional-hazards Cox models.

At initiation of dialysis, mean eGFR increased from 9.3 ± 5.2 mL/minute/1.73 m2 in 2001 to 10.2 ± 7.1 mL/minute/1.73 m2 in 2007 (P < .001). During the same period, the proportion of early dialysis initiations increased from 28% (95% confidence interval [CI], 27% - 30%) to 36% (95% CI, 34% - 37%). Among those starting dialysis early, mean GFR at initiation was 15.5 ± 7.7 mL/minute/1.73 m2 vs 7.1 ± 2.0 mL/minute/1.73 m2 among those who started dialysis late.

For early vs late initiation of dialysis, the unadjusted hazard ratio (HR) for death was 1.48 (95% CI, 1.43 - 1.54). After adjustment for demographic factors, serum albumin, primary cause of end-stage renal disease, type of vascular access, comorbid conditions, late referral, and transplant status, the HR for death decreased to 1.18 (95% CI, 1.13 - 1.23). Difference in mortality per 1000 patient-years between starting dialysis early vs late decreased after 1 year of follow-up but persisted and began increasing again after 24 months of follow-up, with significant differences at 6, 12, 30, and 36 months.

"In Canada, dialysis is being initiated at increasingly higher levels of ...GFR," the study authors write. "A higher GFR at initiation of dialysis is associated with an increased risk of death that is not fully explained by differences in baseline characteristics."

Limitations of this study include biases related to observational design, those associated with the use of registry data, and potential confounding by indication.

"The consistent absence of a survival benefit with early initiation of dialysis across a variety of study designs, populations and health care delivery systems supports the conclusion that early initiation confers no survival benefit, and argues against pre-emptive initiation of dialysis in asymptomatic patients," the study authors conclude. "In contrast to early initiation of dialysis, early referral to a nephrologist is consistently associated with better survival. Further research is needed to determine the objective signs, symptoms and laboratory test results associated with increased mortality and decreased quality of life among patients with advanced renal failure."

CMAJ. Published online December 6, 2010.
Clinical Context

Examination of dialysis registers has shown that the procedure is being initiated earlier at increasingly higher levels of eGFR. In the United States, the National Kidney Foundation has suggested that initiation of dialysis be considered before stage V chronic kidney disease (eGFR < 15 mL/minute/1.73 m²). However, studies have suggested no survival benefit in patients with early initiation of hemodialysis.

This is a cohort study of Canadian patients who initiated hemodialysis early vs late to examine recent trends in timing of initiation and the association with mortality risk.