In this single center study of consecutive incident dialysis patients, we identified that a proportion of patients with a normal eGFR or early stage CKD (1 to early stage 4), initiated dialysis after an illness that induced a permanent, rapid loss of eGFR. Virtually all of these patients used a CVC as initial dialysis access. While this acute start patient group made up only a small percentage of all dialysis starts, they were at an increased risk for mortality compared to chronic start patients. Finally, CVCs were associated with a trend to increased mortality, but amongst chronic dialysis starts, the mortality risk of CVCs was attenuated and comparable to patients with alternative access.
For the chronic start patients, there are potential reasons that dialysis access was not associated with increased mortality, a finding in contrast to large registry studies [2, 6]. An association between mortality and AKI/ACKD leading to ESRD has been demonstrated in previous studies [13, 14, 27]. The majority of these patients initiate dialysis with a CVC. However, even patients with non-dialysis requiring AKI have a higher mortality risk compared to those without AKI . This emphasizes that the association between CVC access and mortality (in AKI patients who do not recover kidney function) may be the result of AKI itself. Alternatively AKI or ACKD may negatively impact on other factors that have been known to influence mortality in dialysis patients, such as residual renal function [29, 30]. If these patients are not excluded from studies of incident dialysis and mortality, the mortality risk of CVCs may be overestimated. Another consideration is that the comparable survival for CVC vs. AVF/PD catheter access after exclusion of acute starts may be related to access conversion. While it was not the intention of this study, it has been shown that conversion from a CVC to an AVF after dialysis initiation is associated with increased survival .
The suggestion that the CVC associated mortality may be overestimated is further supported in our analysis of cause of death. Only 7/148 patient deaths (5 %) were clearly a direct result of the CVC itself (infection or vascular thrombosis). 4 of the 7 patient deaths were acute starts, a population who may be at an increased risk of hospital acquired bacteremia from other sources. While cause of death may have been subject to classification error, we were able to corroborate data with electronic records in this study. In contrast, registry studies may not always have access to individual records to confirm or refute cause of death .
However, even if CVC related mortality was underestimated in this study, complete avoidance of CVCs may be unrealistic and unachievable for a large number of incident dialysis patients. The three chronic start patients who died of catheter sepsis had largely unavoidable reasons for CVC use including previous access failure and patient refusal of alternative access. Furthermore, a recent study determined that the majority of late referred ESRD dialysis starts are unavoidable , and it can be assumed that many of these patients start dialysis with a CVC. This assumption was confirmed in our study, namely, that a sizeable proportion of patients develop ESRD after a rapid loss of eGFR, a setting in which alternative access is not anticipated. The notion that CVCs should be avoided at all costs also needs to be reconsidered in light of AVF success rates. Fistulas continue to have a high primary non-function rate [34–36]. The utility of AVFs is also questioned in many older patients. This is in part due to the high competing risk of death prior to dialysis access and the significant early mortality risk of elderly CKD patients with functioning access after the start of dialysis [37, 38]. Overall, these scenarios suggest that while AVF and PD catheter access are preferred, there will still be considerable numbers of dialysis starts that will not be optimal despite our best efforts [39, 40].
The findings of our study need to be compared to other cohort studies examining the association between dialysis access, acute start and mortality. The findings in our study were similar to a recent analysis of Veterans Affairs (VA) patients in which a “catastrophic loss of eGFR” (defined as loss from levels >60 ml/min/1.73 m2 within 6 months or less) was associated with early mortality . While those patients initiated dialysis at a higher eGFR than our study (in part because the definition of predialysis eGFR was different), both studies highlight the importance of a rapid eGFR decline and its impact on mortality. In a large French REIN registry analysis of incident dialysis patients with congestive heart failure (CHF), despite excluding unplanned dialysis starts, CVC use was still associated with a statistically significant mortality HR of 1.35 (95 % CI 1.22-1.49) . However, unlike the REIN study, our cohort had both CHF and non-CHF patients. In addition, the definition of an acute start differs from the unplanned definition used in REIN cohort studies [42, 43]. We only classified AKI/ACKD patients who started dialysis as “acute starts”, but not those with previously undiagnosed or uninvestigated late stage CKD who presented late. While speculative, the latter may be a group of “survivors” (by virtue of being able to survive to the point of getting dialysis access) that would have been excluded from the REIN chronic cohort of planned dialysis starts.
There are limitations to this study. Three-month eGFR measurements were not available in all patients and ultrasound or patient history may be inaccurate in differentiating acute and chronic kidney disease. However, using the criteria in our definition, and considering the acute events in this patient group (primarily RPGN and myeloma) it was not illogical to classify patients as an acute start when eGFRs were not readily available. While the accuracy of our ESRD database is enhanced by its use of detailed electronic records, we acknowledge that there may have been some patients with AKI and early mortality that were misclassified as ESRD patients, or ESRD acute starts that were not included in this study. Because of a lack of frequent eGFR measurements in all patients, it was not possible to accurately capture the rate of eGFR decline and incorporate it into the definition. Some authorities may advocate for placement of a fistula or PD catheter at an eGFR >25 ml/min/1.73 m2 if a patient were experiencing a rapid decline in eGFR. However, a sensitivity analysis using a more conservative eGFR cutoff of >30 ml/min/1.73 m2 (corresponding to the lower limit of stage 3 CKD), did not change the results of our study. A final limitation of our definition of acute start is that fistulas or PD catheters can be placed and accessed within 3 months of identifying a need for dialysis. However, our population also required an acute illness event to precipitate the decline in eGFR prior to dialysis initiation. Therefore, most physicians would be unprepared to institute optimal access placement in this population. This would be true for patients with a recent cardiac/septic event or admission in an individual with potentially reversible AKI (i.e. myeloma or RPGN). In addition to the study population, there are other limitations inherent to the study design. Despite controlling for multiple variables, there is the possibility of residual confounding and bias. It is possible that a larger study may detect a small, persistent, residual early mortality risk associated with CVCs. Furthermore, while we attempted to capture all of the CVC related deaths, 15 % of deaths amongst chronic start patients were of unknown cause. It is possible that additional catheter-related septic deaths were missed in this group.
It should be emphasized that while this study suggests that the mortality attributed to CVCs needs to be examined after consideration of an “acute start”, we are not suggesting that CVCs are optimal dialysis access. We acknowledge that our patients may have developed CVC complications that indirectly led to alternative causes of death or morbidity. Moreover, given CVCs are associated with significant morbidity and cost [44–47], there should be concerted efforts to obtain alternative access in prevalent dialysis patients.