There are two competing principles that feed into the decision on the timing of initiation of long-term dialysis for patients with end-stage kidney disease. On the one hand is the premise that maintenance dialysis has the potential to improve the quality and quantity of life of most patients with end-stage kidney disease. On the other hand, long-term dialysis imposes a significant burden of treatment as patients have to make substantial and sustained changes to their lives to accommodate the dialysis schedule. Undoubtedly, maintenance dialysis should be initiated at that stage in a patient’s illness when the risk from the untreated uremic syndrome is greater than the burden of treatment. The question that follows is what is that stage in a patient’s illness? Is it numbers or symptoms (Table 1)?
Numbers and symptoms useful in deciding the appropriate timing of initiation of maintenance dialysis in patients with advanced CKD
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Numbers and symptoms useful in deciding the appropriate timing of initiation of maintenance dialysis in patients with advanced CKD
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The accumulated evidence to date suggests that numbers [estimated or measured glomerular filtration rate (eGFR)] should not be the sole guide for the timing of initiation of dialysis. The most important reason for this conclusion is that there does not appear to be any meaningful difference in health outcomes in patients who initiate maintenance dialysis at different levels of GFR. In the only randomized controlled clinical trial undertaken to test this hypothesis, the Initiating Dialysis Early and Late (IDEAL) study, 828 patients with end-stage kidney disease were randomized to initiate dialysis at creatinine clearance, by the Cockcroft–Gault formula, of either 10–14 or 5–7 ml/min/1.73 m2 [1]. At a median follow-up of 3.6 years there was no difference in all-cause or cardiovascular mortality, hospitalizations, health related quality of life or total health care costs between the two groups [1, 2]. Critics of the study have pointed to the small separation that the investigators were able to achieve in the GFR at the time of initiation of dialysis between the two randomized groups. Yet, a handful of observational studies provide corroborative evidence for the key findings from the IDEAL study. Unlike studies with eGFR, observational studies that have used measured GFR as the exposure have demonstrated similar or lower all-cause mortality in patients that initiate dialysis at a higher eGFR compared with those with a lower eGFR [3, 4].
With these studies as a backdrop, many experts and clinical practice guidelines recommend that maintenance dialysis should be initiated only when the patient develops uremic symptoms [5]. On the surface, these recommendations seem quite reasonable. However, abundant caution is warranted for several reasons. First, many uremic symptoms are subtle; patients often adapt to a lower level of functioning and thence do not explicitly experience or endorse the common checklist of symptoms such as fatigue or low level of energy. It is imperative for the clinician to carefully tease these symptoms out to best guide clinical decision making. Second, dialysis treatment does not improve all uremic symptoms—the frequency and severity of symptoms in general in patients undergoing maintenance dialysis is no different in patients with chronic kidney disease (CKD) prior to initiation of dialysis [6]. Which symptoms improve with maintenance dialysis is not well studied—the limited evidence suggests that at least anorexia and symptoms of volume overload improve in the months following initiation of dialysis [7, 8]. Elicitation of these symptoms should thus be prioritized over others when evaluating a patient's need to begin maintenance dialysis. Third, some symptoms have greater health effects than others. In one of the few longitudinal studies that span the pre- and postdialysis initiation period, patients that initiated dialysis secondary to volume overload had the greatest risk for death [9]. This suggests that patients with volume overload necessitating dialysis initiation are particularly vulnerable and the threshold for recommending long-term dialysis in these patients may be lower than in similar euvolemic patients.
It is also important to point out that there are important considerations other than numbers and symptoms that should be incorporated in the clinical decision making around the timing of initiation of maintenance dialysis. There are patients who may choose a nondialytic treatment for their end-stage kidney disease, such as maximum conservative care or preemptive kidney transplantation. Thus it is important for clinicians to periodically ensure that the treatment choices (dialytic or non-dialytic) are closely aligned with patients’ goals of care. Furthermore, the first dialysis treatment for many patients around the world is urgent and often unplanned, not infrequently with a less-preferred dialysis access, such as a central venous catheter, or a dialysis modality other than the one of choice [10]. Hence the efforts to identify the most appropriate time to initiate dialysis should occur in parallel with dialysis modality education, decision support for selection of dialysis modality, timely placement of an appropriate dialysis access and planned initiation of dialysis.
Based on the evidence reviewed above, it is reasonable to conclude that in otherwise asymptomatic patients with low numbers, dialysis can be safely postponed; the time available with this delay should be best used for preparing for dialysis, including modality education, decision support and timely placement of appropriate dialysis access. Conversely, in patients with advanced CKD and difficult-to-manage uremic manifestations, including but not limited to volume overload or electrolyte abnormalities, dialysis should not be denied simply because the GFR is too high. The experience from patients in the IDEAL study randomized to late start showed that they developed uremic symptoms at a mean creatinine clearance of 9.8 ml/min/1.73 m2 [or Modification of Diet in Renal Disease GFR of 7.2 ml/min/1.73 m2] [1].
To conclude, the timing of initiation of dialysis remains within the realm of the art of medicine and should be individualized, guided by a careful and frequent clinical assessment of both numbers and symptoms in partnership with the patients and their caregivers (Figure 1).
Considerations at the bedside on deciding the optimal time to initiate maintenance dialysis in patients with end-stage renal disease
CONFLICT OF INTEREST STATEMENT
None of the authors declare a competing financial interest regarding this study.
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