Major Adverse Kidney Events in Youth on CKRT

Because children, adolescents, and young adults with critical illness have a high risk of developing acute kidney injury (AKI) and disorders of fluid balance, they are increasingly treated with continuous kidney replacement therapy (CKRT). However, little has been reported about longer-term outcomes for this patient population, such as persistent kidney dysfunction, continued need for dialysis, or death.

To address this knowledge gap, Dana Y. Fuhrman, DO, MS, and fellow researchers sought to characterize the incidence and risk factors, including patterns of liberation from CKRT, associated with major adverse kidney events 90 days after CKRT initiation (MAKE-90) in young patients listed in the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease registry. Their results appeared in JAMA Network Open.

The researchers selected subjects aged 0 to 25 years and requiring CKRT due to AKI or fluid overload. They categorized patients into one of three liberation categories based on attempts to liberate within the first 28 days of CKRT: (1) liberated: patients who did not receive CKRT or another dialysis modality for 72 or more hours after discontinuing CKRT; (2) reinstituted: patients who resumed CKRT or another dialysis modality within 72 hours of attempting liberation; (3) not attempted: patients who did not attempt CKRT liberation within the first 28 days after initiating CKRT. The primary outcome was MAKE-90, including death or persistent kidney dysfunction (dialysis dependence or ≥25% decline in estimated glomerular filtration rate from baseline).

The study included 969 patients (529 males [54.6%]; median [IQR] age, 8.8 [1.7-15.0] years; 16 American Indian [1.9%]; 40 Asian or Pacific Islander [4.7%]; 127 Black [14.9%]; 652 White [76.4%]; and 160 Hispanic [18.6%]). MAKE-90 occurred in 630 (65%) patients. Of those, 368 (58.4%) patients fulfilled the MAKE-90 criteria via mortality, 91 (14.4%) were dialysis-dependent, and 262 (41.6%) had persistent kidney dysfunction. Patients with no prior comorbidities comprised the smallest proportion of the MAKE-90 population (85 [13.5%]). Patients with cardiac (145 [23.0%]), oncologic (161 [25.6%]), or immunologic (123 [19.5%]) comorbidities constituted the largest proportions of the MAKE-90 population.

Patients who successfully liberated from CKRT within 28 days had a 68% lower chance of meeting MAKE-90 criteria (adjusted odds ratio [aOR], 0.32; 95% CI, 0.22-0.48) compared with those who had CKRT reinitiated after attempting liberation. Patients who were successfully liberated had 98% lower odds of meeting the criteria for MAKE-90 compared with patients for whom liberation was never attempted (aOR, 0.02; 95% CI, 0.01-0.04). A longer period from intensive care unit (ICU) admission to initiation of CKRT was independently associated with increased chances of MAKE-90 (aOR for 6 days vs 1 day, 1.07; 95% CI, 1.02-1.13). Having a cardiac comorbidity was associated with 1.60-fold increased odds of MAKE-90 (aOR, 1.60; 95% CI, 1.08-2.37). The absence of any comorbidity was protective against MAKE-90 (aOR, 0.48; 95% CI, 0.30-0.76).

MAKE-90 incidence varied among the liberated group (110 [17.5%]), reinstituted group (179 [28.4%]), and not attempted group (341 [54.1%]). At 90 days, there was a statistically significant difference in mortality among patients who successfully liberated (26 [7.8%]), required reinstitution of CKRT after a liberation attempt (42 [14.6%]), and in whom liberation was not attempted (278 [77.9%]; P<.001). There was also a significant difference in mortality when comparing the successfully liberated group with the group that had CKRT reinstituted (log-rank P=.006). Individuals who successfully liberated had the lowest probability of MAKE-90 (33.6%; 95% CI, 25.6%-42.7%) compared with the not attempted group (95.6%; 95% CI, 93.3%-97.5%) and reinstituted group (61.0%; 95% CI, 51.2%-69.9%).

The study authors acknowledged several limitations. It is possible that liberation pattern does not directly contribute to MAKE but is instead a consequence of disease severity or that pathophysiologic mechanisms contributing to adverse outcomes after CKRT are independent of severity of illness. The study is retrospective, using data self-reported by participating centers, which could result in selection bias. The researchers included multiple markers of severity of illness in their analysis, but it is possible that there was residual confounding present. Only the first attempt at liberation was documented, so it is possible that the researchers missed patients who successfully liberated after a subsequent attempt. All hospitals included were tertiary or quaternary, which may have limited generalizability to resource-limited settings. The type I error rate may have surpassed the minimal level given that no adjustments for multiple testing were performed. Only multivariable results using complete data were reported, and 34 patients with missing data were excluded. Finally, the definition of liberation status may have introduced periods of immortal time during which patients could not experience the outcome, resulting in some bias in researchers’ estimates.

In summary, the study found that MAKE-90 were common in young patients receiving CKRT, with more than two-thirds experiencing them. The researchers also successfully identified risk factors for MAKE-90, as they noted: “We found that successful liberation from therapy within 28 days was associated with lower odds of MAKE-90. Our study findings further suggest that cardiac diagnoses and increased duration between ICU admission and CKRT initiation contribute to MAKE at 90 days. Our study results support the need for future prospective studies exploring a causative relationship between CKRT parameters and clinically relevant outcomes in children, adolescents, and young adults.”

Source: JAMA Network Open