What drives early dialysis initiation and how do we optimize timing of RRT?

Timing of dialysis initiation has been in the spotlight in recent years (1). During the last decade, there has been a trend toward initiation of chronic dialysis at higher levels of eGFR (2). The reason for increased attention to the topic is accumulating evidence that early dialysis initiation does not improve patient outcomes and results in unwarranted costs. In observational studies, higher eGFR at dialysis initiation has been associated with higher mortality risk after initiation, independent of patient characteristics including nutritional status (1,3). The Initiating Dialysis Early and Late (IDEAL) trial recently reported that compared with a strategy of delayed dialysis initiation, earlier initiation in patientswith advancedCKDwasnot associatedwith improved survival (4) or quality of life, but was associatedwith increased costs (5). The percentage of patients who initiate RRT at higher eGFR values continued to rise through 2009, both in the United States (6) as well as in Canada. Several factors have been hypothesized to contribute to the reported increase in eGFR at dialysis initiation, including greater acceptance of older and sicker patients with multiple comorbidities for dialysis intervention, a belief that of earlier dialysis initiation is associated with patient benefit, eGFR reporting and reliance on eGFR values to guide timing of dialysis initiation,misinterpretation of clinical practice guidelines, a desire to simplify management of CKD complications, and a greater financial reimbursement to providers associated with dialysis compared with CKD care (1,2). Prior studies have evaluated both patient and provider characteristics associated with timing of dialysis initiation (2,7). In this issue of CJASN, Sood et al. aimed to determine howpatient, facility, and geographic characteristics influence the variation of eGFR at dialysis initiation across Canada (8). The authors observed that patient-related factors accounted for.95% of the explained variability of eGFR at dialysis initiation (8). Many of the specific patient characteristics associated with earlier dialysis initiation are similar to those previously observed in United States cohorts (2,7,9), and include female sex and presence of comorbidities. Prior studies have also suggested that patients with congestive heart failure initiate dialysis at higher eGFR values, likely to assist in the management of the patient’s volume status (2,7). It is likely that in Canada, similar to the United States, acceptance of older and sicker patients for dialysis therapy has contributed to the trend of rising eGFR at dialysis initiation because these patients typically are unable to tolerate uremia to the same degree as younger patients and they may have artificially higher eGFR estimates from their reduced muscle mass. The study by Sood et al. also demonstrated an association between lower phosphorus levels and earlier dialysis initiation (8). Although this may represent poor nutritional status, it may also represent residual confounding. Because phosphorus is renally cleared, it may be that patients with a greater eGFR have greater clearance of phosphorus and lower serum levels. Use of peritoneal dialysis (PD) as the renal replacement modality was associated with higher eGFR at initiation compared with hemodialysis. In a subgroup analysis of the IDEAL trial limited to participants who planned to commence PD, rates of death, cardiovascular events, and peritonitis were not different between early and delayed start arms. However, the proportion of patients planning to commence PD who actually initiated dialysis with PD was higher in the early start group (80% versus 70%; P50.01) (10). The need for careful planning of PD catheter insertion and training for PD before urgent indications for dialysis arise likely pushes providers to initiate patients who desire to commence PD earlier. Because residual renal function is important for PD patient outcomes, avoidance of hemodialysis as the first dialysis modality is highly desirable. Further research is needed that would identify optimal timing for PD catheter placement and patient training, while avoiding unnecessary time on dialysis as well as missed PD opportunities. Variability of eGFR at dialysis initiation in the Canadian cohort was largely explained by the patient characteristics,withminimal geographicvariation. This finding is somewhat surprising. Ina studyof factors that influence the decision to start dialysis among European nephrologists, nephrologists from countrieswith a high incidence of treated ESRD chose higher eGFR values for dialysis initiation and were more likely to initiate their patients early in the presence of advanced age and chronic conditions (11). Similarly, in the United States, the incidence of treated ESRD, particularly among elderly patients and patients with multiple comorbid conditions, is highest in regions with the highest intensity of end-of life care (12). Slinin et al. found a weak association between density of nephrologists and Minneapolis Veterans Affairs Health Care System and Department of Medicine, University of Minnesota, Minneapolis, Minnesota