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CRRT Timing Tied to Survival in Children with AKI, Volume Overload

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Unlike in adults, earlier initiation of continuous renal replacement therapy (CRRT) might be life-saving for children with acute kidney injury (AKI) or volume overload in the intensive care unit, according to investigators. 

In a study of 969 pediatric critical care patients from the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry, 630 patients experienced death, dialysis dependence, or a more than 25% decline in estimated glomerular filtration rate (eGFR) within 90 days, collectively termed MAKE-90. CRRT initiation appeared significantly delayed among those who experienced MAKE-90 compared with those who did not by a median 3 vs 2 days after ICU admission, Katja M. Gist, DO, of Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine in Ohio, and colleagues reported in JAMA Network Open.

Each 1-day delay in CRRT initiation was significantly associated with 3% increased odds of MAKE-90 and 4% increased odds of 90-day mortality. CRRT delayed for 6 days after ICU admission was significantly associated with 21% increased odds of MAKE-90 compared with CRRT performed on day 1.

The mortality rate at 90 days was significantly higher among pediatric patients with late CRRT initiation (more than 2 days after ICU admission) than among those with early initiation (2 or fewer days after ICU admission): 41.7% vs 33.7%.

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“These findings are particularly profound when one considers that the early CRRT initiation group was sicker, as measured by higher PRISM-III scores at ICU admission. This highlights the continued need to develop stratification tools aimed at identifying at-risk patients early in their ICU course,” Dr Gist’s team wrote.

Among the 601 pediatric patients who survived, 44% had persistent kidney dysfunction, and of these, 35% were dialysis dependent.

The study lacked information on when AKI occurred (prior to or during ICU admission), AKI etiology, and the indication for CRRT initiation, so further research is needed to determine optimal timing of CRRT in children as well as dose, fluid removal, and anticoagulation.

Results from a separate study suggest that correcting serum creatinine for fluid balance may improve diagnosis of AKI in infants. In a post hoc analysis of the PENUT randomized trial ( Identifier: NCT01378273) including 923 premature infants, fluid correction increased the proportion diagnosed with AKI from 23.3% to 33.9%. In multivariable analysis, fluid-corrected AKI was significantly associated with 2.2- and 2.1-fold increased odds of ventilation and severe bronchopulmonary dysplasia, respectively, Michelle C. Starr, MD, MPH, of Indiana University School of Medicine in Indianapolis, and colleagues reported in JAMA Network Open. Fluid-corrected serum creatinine was defined as serum creatinine multiplied by fluid balance (calculated as percentage change from birth weight) divided by total body water (estimated as 80% of birth weight).

An automated clinical decision support (CDS) program combining risk stratification and AKI biomarker assessment can reduce pediatric CRRT morbidity, Stuart L. Goldstein, MD, of the Center for Acute Care Nephrology at Cincinnati Children’s Hospital in Ohio, and colleagues reported in Kidney International Reports. The CDS program incorporated renal angina index (RAI) at 12 hours after ICU admission to guide urinary neutrophil gelatinase-associated lipocalin (uNGAL) testing with further furosemide stress testing, if warranted, to predict severe AKI.

In the Trial in AKI using NGAL and Fluid Overload to optimize CRRT Use (TAKING FOCUS 2), 286 patients aged 3 months to 25 years were admitted to the hospital’s pediatric ICU during 2014-2021. Of these, 178 patients received CRRT.

Fluid intake, diuretic management, and initiation of CRRT were informed by the decision support algorithm to prevent fluid accumulation exceeding 15% of body weight. Management was ultimately decided by clinicians, however.

Implementation of the CDS program was significantly associated with a 2-day shorter median time from ICU admission to CRRT initiation, and a lower rate of 15% or greater fluid accumulation prior to CRRT, the investigators reported. ICU length of stay (LOS) after CRRT discontinuation and total ICU LOS were 6 and 11 days shorter for CRRT survivors, respectively.

Rates of survival to ICU discharge after CRRT discontinuation were higher after implementation, according to Dr Goldstein’s team.

Future studies will examine disease-specific RAI thresholds, alternate urinary biomarkers, and long-term progression to hypertension, proteinuria, and chronic kidney disease.


Gist KM, Menon S, Anton-Martin P, et al; WE-ROCK investigators. Time to continuous renal replacement therapy initiation and 90-day major adverse kidney events in children and young adults. JAMA Netw Open. Published online January 2, 2024. doi:10.1001/jamanetworkopen.2023.49871

Starr MC, Griffin RL, Harer MW, et al. Acute kidney injury defined by fluid-corrected creatinine in premature neonates: a secondary analysis of the PENUT randomized clinical trial. JAMA Netw Open. 2023 Aug 1;6(8):e2328182. doi:10.1001/jamanetworkopen.2023.28182

Goldstein SL, Krallman KA, Roy JP, et al. Real-time acute kidney injury risk stratification-biomarker directed fluid management improves outcomes in critically ill children and young adults. Kidney Int Rep. 2023 Sep 22;8(12):2690-2700. doi:10.1016/j.ekir.2023.09.019

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Schedule30 May 2024