Study Details Consequences of Delayed CRRT Initiation in Children, Young Adults

Katja Gist, DO

Credit: Doximity

Delayed initiation of continuous renal replacement therapy (CRRT) is associated with an increased risk of adverse events, including death, dialysis dependence, and persistent kidney dysfunction at 90 days, according to findings from a multinational retrospective cohort study.

A secondary analysis of data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry for children and young adults receiving CRRT for acute kidney injury or volume overload showed each 1-day delay in initiation was associated with 3% greater odds of major adverse kidney events at 90 days (MAKE-90).¹

A method of slower, continuous dialysis to allow solute and fluid homeostasis, CRRT is generally preferred for hemodynamically unstable patients and is often employed in the ICU. However, optimal timing for therapy initiation is not well understood, and research regarding when to begin CRRT is especially sparse for children. Although early initiation may allow for early correction of electrolyte abnormalities, volume status, and azotemia, the impact of time to initiation remains speculative.²

“Multiple randomized trials in adults evaluating the effect of timing of initiation on CRRT outcomes have yielded conflicting results. In children, there are no randomized trials evaluating the timing of CRRT initiation and outcomes, and most studies are small, single center in design with varied timing definitions,” wrote investigators.¹ “This represents a substantial gap in our knowledge and opportunity to improve outcomes in pediatric critical care nephrology.”

To address this gap in research, Katja Gist, DO, codirector of the Center for Acute Care Nephrology at Cincinnati Children's Hospital Medical Center, and a team of investigators retrospectively examined data from the international multicenter WE-ROCK registry from 2015-2021 for children and young adults receiving CRRT for acute liver injury or volume overload at 32 centers across 7 countries. In total, 969 patients were enrolled in the present study, 440 (45.4%) of which were female with a mean age of 8.8 (Interquartile range [IQR], 1.7-15.0) years.¹

The primary exposure variable was time to CRRT initiation from intensive care unit admission. Investigators categorized initiation as a binary variable based on the cohort’s median time to CRRT, with ≤ 2 days defined as early and > 2 days defined as late.¹

The primary outcome of interest was MAKE-90, including death, dialysis dependence, or persistent kidney dysfunction, defined as ≥ 25% decline in estimated glomerular filtration rate (eGFR) from baseline. Secondary outcomes included ventilator-free days and ICU-free days assessed during the first 28 ICU days.¹

Among the cohort, the most common admission category was shock/infection/trauma (37.2%). Baseline kidney function was measured for 541 patients (55.8%) and was a median of 0.4 (IQR, 0.22-0.62) mg/dL. The median ventilator-free days was 12 (IQR, 0-28) and median ICU-free days was 0 (IQR, 0-0).¹

The median time to CRRT initiation was 2 (IQR, 1-6) days and median therapy duration was 6 (IQR, 3-14) days. There were 514 patients (52.5%) who initiated therapy within ≤ 2 days of ICU admission, 314 (61.1%) of whom had MAKE-90 compared to 315 of 465 patients with late initiation (67.7%; P = .054).¹

Of the 630 patients affected by MAKE-90, 368 (58.4%) died. Persistent kidney function was prevalent among 262 (43.6%) of the 601 patients who survived and 91 (34.7%) were dependent on dialysis.¹

In the generalized propensity score–weighted regression, there were approximately 3% higher odds of MAKE-90 for each 1-day delay in CRRT initiation (odds ratio [OR], 1.03; 95% Confidence interval [CI], 1.02-1.04).¹

Investigators pointed out mortality at 90 days was significantly greater among those with late initiation (42.5%) compared to early initiation (33.7%; P = .01). Further analysis revealed mortality was significantly greater among the CRRT > 2 days and volume overload < 10% subphenotype (44.0%) (P < .001). Median ventilator-free days (19 days vs 0 days; P < .001) and ICU-free days (2 days vs 0 days; P < .001) were also reduced among those with late initiation compared to early initiation.¹

The median volume overload at CRRT initiation was 7.4% (IQR, 2.4%-18.1%). Unadjusted median volume overload at CRRT initiation for those who started CRRT > 2 days was 12.5% (IQR, 5.3%-28.7%), and investigators pointed out it was significantly greater than those who started CRRT ≤ 2 days (4.8%; IQR, 1.1%-10.4%) (P < .001).¹

“This analysis of the large multinational WE-ROCK study begins to fill an important gap in the pediatric critical care nephrology literature by providing a detailed analysis of the association of CRRT initiation timing and VO with outcomes. Prospective multicenter studies are needed in children to delineate the appropriate time to initiate CRRT that optimizes survival and reduces long-term morbidity and health care utilization,” investigators concluded.¹

References:

1. Gist KM, Menon S, Anton-Martin P, et al. Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults. Jama Network Open. doi:10.1001/jamanetworkopen.2023.49871
2. Saunders H, Rehan A, Sanghavi DK. Continuous Renal Replacement Therapy. StatPearls. May 8, 2023. Accessed January 2, 2024. https://www.ncbi.nlm.nih.gov/books/NBK556028/