IDEAL Trial Results and Changes in Dialysis Initiation Timing in Canada

The optimal time to initiate dialysis for the treatment of kidney failure remains uncertain. Renal recovery is rare following dialysis initiation and patients receiving dialysis treatments are at high risk for morbidity and mortality and a diminishing quality of life. Further, early initiation of dialysis increases healthcare costs and may not provide optimal value from a health system perspective.

Results of the IDEAL (Initiating Dialysis Early and Late) randomized clinical trial were published in April 2010. In the IDEAL trial, patients with predialysis chronic kidney disease were randomized to planned initiation of dialysis at eGFR 10 to 14 mL/min/1.73 m² (early start) or to initiation of dialysis at eGFR 5 to 7 mL/min/1.73 m² (late start). Trial results suggested there was no association between earlier initiation of dialysis and a statistically significant difference in survival or other clinical outcomes such as cardiovascular events and infections.

Researchers in Canada, led by Thomas W. Ferguson, MSc, recently conducted an interrupted time series analysis study to examine the association between the publication of results of the IDEAL trial and the proportion of patients in Canada who initiated dialysis early (eGFR ≥10.5 mL/min/1.73 m²). Results of the analysis were reported online in JAMA Internal Medicine

The primary outcome of interest was the proportion of early dialysis starts. Secondary outcomes were the proportions of acute inpatient dialysis starts, patients who started dialysis using a home modality, and patients receiving hemodialysis who started with an arteriovenous access. The researchers utilized data from the Canadian Organ Replacement Register.

The analysis model included the trend before the IDEAL trial publication, an evaluation of the change in this trend after publication, and the immediate consequence of publication. The pretrial period was 56 months (January 1, 2006, to August 31, 2010). Following publication of the trial in August 2010, a 6-month grace period was included in the model (September 1, 2010, to February 28, 2011). The posttrial period was 58 months (March 1, 2011, to December 31, 2015).

Eligible participants were ≥18 years of age with incident chronic dialysis between January 1, 2006, and December 31, 2015, in Canada. Patients from the province of Quebec were excluded due to privacy laws that preclude submission of deidentified data without first-person consent. Eligibility included at least 90 days of nephrologist care prior to initiation of dialysis and a recorded eGFR at dialysis initiation.

The final study cohort included 28,468 patients; 60.9% (n=17,342) were male and mean age was 64.8 years. Compared with the pretrial population, patients in the posttrial period were more likely to be male; had lower serum hemoglobin, lower serum albumin, and higher serum phosphate levels at dialysis initiation; had more days of predialysis care; had higher body mass index; and had more comorbid conditions.

Of the total cohort, 36.3% of patients (n=10,323) initiated dialysis during the study period with an eGFR at initiation higher than 10.5 mL/min/1.73 m². The proportion of early dialysis starts was 39.0% (95% confidence interval [CI], 38.1%-39.9%) in the pretrial period and 34.0% (95% CI, 33.3%-34.7%) in the posttrial period. During the pretrial period, there was a statistically significant increasing trend in the monthly proportion of early dialysis (adjusted rate ratio, 1.002; 95% CI, 1.001-1.004; P=.004). There was a statistically significant decrease in the proportion of early states immediately after the pretrial and grace periods (rate ratio, 0.874; 95% CI, 0.818-0.933; P<.001). There was also a statistically significant change in trend between the pretrial and posttrial periods (rate ratio, 0.994; 95% CI, 0.992-0.996; P<.001).

During the study period, 26.9% of patients (n=7166) initiated dialysis as acute inpatients. In the pretrial period, the proportion of acute inpatient starts was 24.0% (95% CI, 23.2%-24.8%) compared with 28.9% (95% CI, 28.2%-29.6%) in the posttrial period. There was no statistically significant trend in the proportion of acute inpatient initiations in the pretrial period, no statistically significant immediate consequence was observed, and no statistically significant change in trend between the pre- and posttrial periods was observed.

A total of 7066 patients (24.8%) initiated dialysis using a home modality during the study period. In the pretrial period, 26.8% of patients initiated dialysis with a home modality, compared with 23.1% in the posttrial period. There was no statistically significant trend in the proportion of dialysis initiations with a home modality in the pretrial period, no statistically significant immediate consequence, and no statistically significant change in trend between the pretrial and posttrial periods observed.

During the study period, 21,054 patients (74.0%) initiated hemodialysis. Of those, 26.1% (n=5497) began therapy with an arteriovenous fistula (AVF) or arteriovenous graft (AVG) access. In the pretrial period, 27.6% of patients initiated dialysis with an AVF or AVG, compared with 25.1% in the posttrial period. There was a statistically significant decrease in the proportion of hemodialysis patients initiating therapy with an AVF or AVG in the pretrial period. Following the pretrial and grace periods, there was no statistically significant immediate consequence, and no statistically significant change in trend between the pretrial and posttrial periods.

There were some limitations cited by the authors: assuming that the IDEAL trial was the major catalyst for changes in dialysis initiation practice; including only patients with evidence of nephrologist care at least 90 days prior to dialysis initiation; and the study occurring in a universal healthcare system, limiting the generalizability of the findings to privately funded healthcare settings.

“This study found that publication of the IDEAL trial appeared to be associated with immediate and sustained change in the timing of dialysis initiation in Canada, excluding Quebec. No statistically significant sustained differences were found in acute inpatient dialysis initiations, the proportion of home-based modality as the initial modality, or the proportion of arteriovenous access construction for hemodialysis,” the researchers said.

Takeaway Points

1. Results of the IDEAL (Initiating Dialysis Early and Late) trial were published in April 2010; there was no association between early initiation of dialysis and improved survival or clinical outcomes.
2. Researchers in Canada recently conducted an analysis to examine the association between the results of the IDEAL trial and the proportion of early dialysis starts in Canada over time.
3. Prior to IDEAL, there was an increasing trend in the monthly proportion of early dialysis starts; following publication of IDEAL results, there was an immediate decrease in the proportion of early dialysis starts. Publication of IDEAL trial results appeared to be associated with a change in the timing of dialysis initiation.