The Association Between Vasopressin and Adverse Kidney Outcomes in Children and Young Adults Requiring Vasopressors on Continuous Renal Replacement Therapy.

OBJECTIVES: Continuous renal replacement therapy (CRRT) and shock are both associated with high morbidity and mortality in the ICU. Adult data suggest renoprotective effects of vasopressin vs. catecholamines (norepinephrine and epinephrine). We aimed to determine whether vasopressin use during CRRT was associated with improved kidney outcomes in children and young adults. DESIGN: Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a multicenter, retrospective cohort study. SETTING: Neonatal, cardiac, PICUs at 34 centers internationally from January 1, 2015, to December 31, 2021. PATIENTS/SUBJECTS: Patients younger than 25 years receiving CRRT for acute kidney injury and/or fluid overload and requiring vasopressors. Patients receiving vasopressin were compared with patients receiving only norepinephrine/epinephrine. The impact of timing of vasopressin relative to CRRT start was assessed by categorizing patients as: early (on or before day 0), intermediate (days 1-2), and late (days 3-7). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1016 patients, 665 (65%) required vasopressors in the first week of CRRT. Of 665, 248 (37%) received vasopressin, 473 (71%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (death, renal replacement therapy dependence, and/or > 125% increase in serum creatinine from baseline 90 days from CRRT initiation), and 195 (29%) liberated from CRRT on the first attempt within 28 days. Receipt of vasopressin was associated with higher odds of MAKE-90 (adjusted odds ratio [aOR], 1.80; 95% CI, 1.20-2.71; p = 0.005) but not liberation success. In the vasopressin group, intermediate/late initiation was associated with higher odds of MAKE-90 (aOR, 2.67; 95% CI, 1.17-6.11; p = 0.02) compared with early initiation. CONCLUSIONS: Nearly two-thirds of children and young adults receiving CRRT required vasopressors, including over one-third who received vasopressin. Receipt of vasopressin was associated with more MAKE-90, although earlier initiation in those who received it appears beneficial. Prospective studies are needed to understand the appropriate timing, dose, and subpopulation for use of vasopressin.

Kidney Health Monitoring in Neonatal Intensive Care Unit Graduates: A Modified Delphi Consensus Statement.

Importance: Kidney disease is common in infants admitted to the neonatal intensive care unit (NICU). Despite the risk of chronic kidney disease (CKD) in infants discharged from the NICU, neither evidence- nor expert-based recommendations exist to guide clinical care after discharge. Objective: To develop recommendations for risk stratification and kidney health monitoring among infants after discharge from the NICU. Evidence Review: At the National Institute of Health-supported Consensus Workshop to Address Kidney Health in Neonatal Intensive Care Unit Graduates meeting conducted in February 2024, a panel of 51 neonatal nephrology experts focused on 3 at-risk groups: (1) preterm infants, (2) critically ill infants with acute kidney injury (AKI), and (3) infants with critical cardiac disease. Using established modified Delphi processes, workgroups derived consensus recommendations. Findings: In this modified Delphi consensus statement, the panel developed 10 consensus recommendations, identified gaps in knowledge, and prioritized areas of future research. Principal suggestions include risk stratification at time of hospital discharge, family and clinician education and counseling for subsequent kidney health follow-up, and blood pressure assessment as part of outpatient care. Conclusions and Relevance: Preterm infants, critically ill infants with AKI, and infants with critical cardiac disease are at increased risk of CKD. We recommend (1) risk assessment at the time of discharge, (2) clinician and family education, and (3) kidney health assessments based on the degree of risk. Future work should focus on improved risk stratification, identification of early kidney dysfunction, and development of interventions to improve long-term kidney health.

Characteristics and outcomes of children ≤ 10 kg receiving continuous kidney replacement therapy: a WE-ROCK study.

BACKGROUND: Continuous kidney replacement therapy (CKRT) is often used for acute kidney injury (AKI) or fluid overload (FO) in children ≤ 10 kg. Intensive care unit (ICU) mortality in children ≤ 10 kg reported by the prospective pediatric CRRT (ppCRRT, 2001-2003) registry was 57%. We aimed to evaluate characteristics associated with ICU mortality using a contemporary registry. METHODS: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry is a retrospective, multinational, observational study of children and young adults aged 0-25 years receiving CKRT (2015-2021) for AKI or FO. This analysis included patients ≤ 10 kg at hospital admission. PRIMARY AND SECONDARY OUTCOMES: ICU mortality and major adverse kidney events at 90 days (MAKE-90) defined as death, persistent kidney dysfunction, or dialysis within 90 days, respectively. RESULTS: A total of 210 patients were included (median age 0.53 years (IQR, 0.1, 0.9)). ICU mortality was 46.5%. MAKE-90 occurred in 150/207 (72%). CKRT was initiated at a median 3 days (IQR 1, 9) after ICU admission and lasted a median 6 days (IQR 3, 16). On multivariable analysis, pediatric logistic organ dysfunction score (PELOD-2) at CKRT initiation was associated with increased odds of ICU mortality (aOR 2.64, 95% CI 1.68-4.16), and increased odds of MAKE-90 (aOR 2.2, 95% CI 1.31-3.69). Absence of comorbidity was associated with lower MAKE-90 (aOR 0.29, 95%CI 0.13-0.65). CONCLUSIONS: We report on a contemporary cohort of children ≤ 10 kg treated with CKRT for acute kidney injury and/or fluid overload. ICU mortality is decreased compared to ppCRRT. The extended risk of death and morbidity at 90 days highlights the importance of close follow-up.

Advocating for the inclusion of kidney health outcomes in neonatal research: best practice recommendations by the Neonatal Kidney Collaborative.

Acute kidney injury (AKI) occurs in nearly 30% of sick neonates. Chronic kidney disease (CKD) can be detected in certain populations of sick neonates as early as 2 years. AKI is often part of a multisystem syndrome that negatively impacts developing organs resulting in short- and long-term pulmonary, neurodevelopmental, and cardiovascular morbidities. It is critical to incorporate kidney-related data into neonatal clinical trials in a uniform manner to better understand how neonatal AKI or CKD could affect an outcome of interest. Here, we provide expert opinion recommendations and rationales to support the inclusion of short- and long-term neonatal kidney outcomes using a tiered approach based on study design: (1) observational studies (prospective or retrospective) limited to data available within a center's standard practice, (2) observational studies involving prospective data collection where prespecified kidney outcomes are included in the design, (3) interventional studies with non-nephrotoxic agents, and (4) interventional studies with known nephrotoxic agents. We also provide recommendations for biospecimen collection to facilitate ancillary kidney specific research initiatives. This approach balances the costs of AKI and CKD ascertainment with knowledge gained. We advocate that kidney outcomes be included routinely in neonatal clinical study design. Consistent incorporation of kidney outcomes across studies will increase our knowledge of neonatal morbidity.

An evaluation of the outcomes associated with peritoneal catheter use in neonates undergoing cardiac surgery: A multicenter study.

Objective: The study objective was to determine if intraoperative peritoneal catheter placement is associated with improved outcomes in neonates undergoing high-risk cardiac surgery with cardiopulmonary bypass. Methods: This propensity score-matched retrospective study used data from 22 academic pediatric cardiac intensive care units. Consecutive neonates undergoing Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 3 to 5 cardiac surgery with cardiopulmonary bypass at centers participating in the NEonatal and Pediatric Heart Renal Outcomes Network collaborative were studied to determine the association of the use of an intraoperative placed peritoneal catheter for dialysis or passive drainage with clinical outcomes, including the duration of mechanical ventilation. Results: Among 1490 eligible neonates in the NEonatal and Pediatric Heart Renal Outcomes Network dataset, a propensity-matched analysis was used to compare 395 patients with peritoneal catheter placement with 628 patients without peritoneal catheter placement. Time to extubation and most clinical outcomes were similar. Postoperative length of stay was 5 days longer in the peritoneal catheter placement cohort (17 vs 22 days, P = .001). There was a 50% higher incidence of moderate to severe acute kidney injury in the no-peritoneal catheter cohort (12% vs 18%, P = .02). Subgroup analyses between specific treatments and in highest risk patients yielded similar associations. Conclusions: This study does not demonstrate improved outcomes among neonates with placement of a peritoneal catheter during cardiac surgery. Outcomes were similar apart from longer hospital stay in the peritoneal catheter cohort. The no-peritoneal catheter cohort had a 50% higher incidence of moderate to severe acute kidney injury (12% vs 18%). This analysis does not support indiscriminate peritoneal catheter use, although it may support the utility for postoperative fluid removal among neonates at risk for acute kidney injury. A multicenter controlled trial may better elucidate peritoneal catheter effects.

Post-natal steroid exposure in very low birthweight neonates and associations with acute kidney injury.

OBJECTIVE: The relationship between adrenal insufficiency (AI), post-natal steroids (PNS) and neonatal acute kidney injury (AKI) remains understudied. We investigated associations between PNS and AKI in very low birthweight (VLBW) neonates, hypothesizing PNS is associated with reduced AKI. STUDY DESIGN: We conducted a single-center retrospective review of VLBW infants comparing those with and without PNS exposure. Associations between PNS exposure and AKI were evaluated using generalized linear mixed-modeling adjusted for confounders. RESULT: Of 567 neonates, 97 (17.1%) were exposed to PNS and 130 (22.9%) experienced AKI. Infants with PNS had lower gestational age, birthweight, Apgar scores, and experienced more AI versus those without PNS (all p < 0.05). PNS was associated with AKI (aRR 1.72, 95% CI 1.09-2.72) though hydrocortisone alone was not. CONCLUSION: PNS exposure, but not hydrocortisone alone, is associated with increased AKI in VLBW neonates. Further analysis is needed to investigate the role of AI and AKI.

Growth in children with nephrotic syndrome: a post hoc analysis of the NEPTUNE study.

BACKGROUND: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression. METHODS: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression. RESULTS: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (- 0.13 ± 1.21 vs. - 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (ß - 7.5 × 10-6, CI - 1.2 × 10-5, - 3 × 10-6, p = 0.001) and incident cases of NS (vs. prevalent) (ß - 1.1, CI - 2.22, - 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (ß 0.16, CI 0.04, 0.29, p = 0.01) over time. CONCLUSION: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score.

Selective Cytopheretic Device Use in Continuous Kidney Replacement Therapy in Children: A Cohort Study With a Historical Comparator.

Rationale and Objective: Critically ill children with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) are at increased risk of death. The selective cytopheretic device (SCD) promotes an immunomodulatory effect at circuit-ionized calcium of <0.40 mmol/L. In an adult CRRT patient study, SCD-treated patients reported improved survival or dialysis independence. We reported safety data from children who received CRRT-SCD therapy and compared outcomes with a historic pediatric CRRT cohort. Study Design: We performed 2 prospective multicenter studies to evaluate the safety and feasibility of SCD in critically ill children. Setting and Participants: Four pediatric institutions enrolled children weighing 10 kg or more with AKI and multi-organ dysfunction receiving CRRT as the standard of care with the SCD-integrated post-CRRT membrane. Exposure: Patients received CRRT-SCD with regional citrate anticoagulation for up to 7-10 days, or CRRT discontinuation, whichever came first. Analytical Approach: We reported serious adverse events among patients and CRRT-SCD-related process and outcome variables. We compared survival to intensive care unit (ICU) discharge rates between the CRRT-SCD cohort and a matched cohort from the prospective pediatric CRRT registry, using odds ratios in multivariable analysis for factors associated with prospective pediatric CRRT patient ICU mortality. To validate these crude analyses, Bayesian logistic regression was performed to assess for attributable benefit-risk assessment of the SCD. Results: Twenty-two patients received CRRT-SCD treatments. Fifteen serious adverse events were recorded; none were SCD-related. Seventeen patients survived till ICU discharge or day 60. Both multivariable and Bayesian analyses revealed a probable benefit of the addition of SCD. Fourteen of the 16 patients surviving ICU discharge reported a normal estimated glomerular filtration rate and no patient was dialysis dependent at 60 days. Limitations: The study had a few limitations, such as (1) a small sample size in the SCD-PED cohort group; (2) unchanging historic control group; and (3) adverse events were not recorded in the control group. Conclusions: The SCD therapy is feasible, safe, and demonstrates probable benefit for critically ill children who require CRRT for AKI.

Only 50% of critically ill children with kidney failure who require the most advanced forms of dialysis survive. One cause of this poor survival is the increased activation of the immune system, which leads to inflammation and organ failure. Reducing the effects of inflammation could improve the survival rate in this very sick population. We studied a device, the selective cytopheretic device (SCD) that lessens the activity of cells in the body that cause inflammation. Twenty-two children received treatment with the SCD put in line with a standard dialysis machine, of which 17 (77%) survived (compared to the expected 11). There were no adverse effects noted with the SCD. Hence, we suggest that the SCD offers an option to improve outcomes in critically ill children with kidney failure.

Neonatal Extracorporeal Membrane Oxygenation: Associations between Continuous Renal Replacement Therapy, Thrombocytopenia, and Outcomes.

INTRODUCTION: The incidence of thrombocytopenia in neonates receiving extracorporeal membrane oxygenation (ECMO) with and without concurrent continuous renal replacement therapy (CRRT) and associated complications have not been well described. The primary aims of the current study were to (1) characterize thrombocytopenia in neonates receiving ECMO (including those treated concurrently with CRRT) and (2) evaluate risk factors (including CRRT utilization) associated with severe thrombocytopenia. In a planned exploratory secondary aim, we explored the association of severe thrombocytopenia with outcomes in neonates receiving ECMO. METHODS: We conducted a retrospective single-center chart review of neonates who received ECMO 07/01/14-03/01/20 and evaluated associations between CRRT, severe thrombocytopenia (platelet count <50,000/mm3), and outcomes (ECMO duration, length of stay, and survival). RESULTS: Fifty-two neonates received ECMO; 35 (67%) received concurrent CRRT. Severe thrombocytopenia occurred in 27 (52%) neonates overall and in 21 (60%) neonates who received concurrent CRRT. Underlying diagnosis, ECMO mode, care unit, and moderate/severe hemolysis differed between those who did and did not receive CRRT. CRRT receivers experienced shorter hospital stays than CRRT non-receivers, but ECMO duration, length of intensive care unit (ICU) stay, and survival did not differ between groups. CRRT receipt was associated with severe thrombocytopenia. Exploratory classification and regression tree (CART) analysis suggests CRRT use, birthweight, and ICU location are all predictors of interest for severe thrombocytopenia. CONCLUSIONS: In our cohort, CRRT use during ECMO was associated with severe thrombocytopenia, and patients who received ECMO with CRRT experienced shorter hospital stays than those who did not receive CRRT. Exploratory CART analysis suggests CRRT use, birthweight, and ICU location are all predictors for severe thrombocytopenia and warrant further investigations in larger studies.

Cardiac Surgery-Associated Acute Kidney Injury in Neonates Undergoing the Norwood Operation: Retrospective Analysis of the Multicenter Neonatal and Pediatric Heart and Renal Outcomes Network Dataset, 2015-2018.

OBJECTIVES: Cardiac surgery-associated acute kidney injury (CS-AKI) is associated with adverse outcomes. Single-center studies suggest that the prevalence of CS-AKI is high after the Norwood procedure, or stage 1 palliation (S1P), but multicenter data are lacking. DESIGN: A secondary analysis of the Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) multicenter cohort who underwent S1P. Using neonatal modification of Kidney Disease Improving Global Outcomes (KDIGO) criteria, perioperative associations between CS-AKI with morbidity and mortality were examined. Sensitivity analysis, with the exclusion of prophylactic peritoneal dialysis (PD) patients, was performed. SETTING: Twenty-two hospitals participating in the Pediatric Cardiac Critical Care Consortium (PC 4 ) and contributing to NEPHRON. PATIENTS: Three hundred forty-seven neonates (< 30 d old) with S1P managed between September 2015 and January 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 347 patients, CS-AKI occurred in 231 (67%). The maximum stages were as follows: stage 1, in 141 of 347 (41%); stage 2, in 51 of 347 (15%); and stage 3, in 39 of 347 (11%). Severe CS-AKI (stages 2 and 3) peaked on the first postoperative day. In multivariable analysis, preoperative feeding was associated with lower odds of CS-AKI (odds ratio [OR] 0.48; 95% CI, 0.27-0.86), whereas prophylactic PD was associated with greater odds of severe CS-AKI (OR 3.67 [95% CI, 1.88-7.19]). We failed to identify an association between prophylactic PD and increased creatinine (OR 1.85 [95% CI, 0.82-4.14]) but cannot exclude the possibility of a four-fold increase in odds. Hospital mortality was 5.5% ( n = 19). After adjusting for risk covariates and center effect, severe CS-AKI was associated with greater odds of hospital mortality (OR 3.67 [95% CI, 1.11-12.16]). We failed to find associations between severe CS-AKI and respiratory support or length of stay. The sensitivity analysis using PD failed to show associations between severe CS-AKI and outcome. CONCLUSIONS: KDIGO-defined CS-AKI occurred frequently and early postoperatively in this 2015-2018 multicenter PC 4 /NEPHRON cohort of neonates after S1P. We failed to identify associations between resource utilization and CS-AKI, but there was an association between severe CS-AKI and greater odds of mortality in this high-risk cohort. Improving the precision for defining clinically relevant neonatal CS-AKI remains a priority.

Corrigendum to "Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK)" [Kidney International Reports Volume 8, Issue 8, August 2023, Pages 1542-1552].

[This corrects the article DOI: 10.1016/j.ekir.2023.05.026.].

Achieving Consensus: Severity-Graded Definitions of Fontan-Associated Complications to Characterize Fontan Circulatory Failure.

BACKGROUND: Fontan physiology leads to chronic changes in other organ systems that may affect long-term survival and the success of heart transplantation. Inadequate assessment and treatment of the extra-cardiac effects of Fontan may contribute to poor outcomes. Severity-graded/ordinal consensus definitions of Fontan complications are lacking, which limits understanding of how Fontan-specific morbidity affects patients' outcomes. METHODS AND RESULTS: A panel of Fontan patient and physiology experts, including pediatric, adult congenital, heart failure, and critical-care cardiology as well as pediatric nephrology, hepatology and psychology, convened to develop definitions of Fontan complications. Definitions were created by using a severity-graded ordinal scale: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, disabling or life threatening. Following definition creation, a second panel of 21 experts in Fontan circulatory failure used a modified Delphi methodology to modify and vote on definitions until consensus (> 90% agreement without recommended further modification) was reached on final definitions. After 3 rounds of modifications and voting, consensus agreement was achieved on all Fontan-specific definitions. The defined complications and morbidities of Fontan include: anatomic Fontan pathway obstruction, cyanosis, systemic venous abnormalities resulting from venous insufficiency, atrial arrhythmia, ventricular arrhythmia, bradycardia, chronic pleural effusions, chronic ascites, protein-losing enteropathy, plastic bronchitis, hemoptysis and pulmonary hemorrhage, sleep apnea, Fontan-associated liver disease, portal and hepatic variceal disease, acute kidney injury affecting clinical treatment, polycythemia, thrombotic disease, recurrent or severe bacterial infection, skin atrophy, adrenal insufficiency, physical impact of previous stroke, mood/behavior disorder, and neurodevelopmental disorder. CONCLUSION: Consensus and severity-graded definitions of Fontan-specific cardiac and extra-cardiac complications were achieved and are available for use in research. They will allow future robust analyses of Fontan patient outcomes.

Longitudinal analysis of blood pressure and lipids in childhood nephrotic syndrome.

BACKGROUND: In the current study, longitudinal BP and lipid measurements were examined in a NEPTUNE cohort of children with newly diagnosed nephrotic syndrome (cNEPTUNE). We hypothesized that hypertensive BP and dyslipidemia would persist in children with nephrotic syndrome, regardless of steroid treatment response. METHODS: A multi-center longitudinal observational analysis of data obtained from children < 19 years of age with new onset nephrotic syndrome enrolled in the Nephrotic Syndrome Study Network (cNEPTUNE) was conducted. BP and lipid data were examined over time stratified by disease activity and steroid exposure. Generalized estimating equation regressions were used to find determinants of hypertensive BP and dyslipidemia. RESULTS: Among 122 children, the prevalence of hypertensive BP at any visit ranged from 17.4% to 57.4%, while dyslipidemia prevalence ranged from 40.0% to 96.2% over a median of 30 months of follow-up. Hypertensive BP was found in 46.2% (116/251) of study visits during active disease compared with 31.0% (84/271) of visits while in remission. Dyslipidemia was present in 88.2% (120/136) of study visits during active disease and in 66.0% (101/153) while in remission. Neither dyslipidemia nor hypertensive BP were significantly different with/without medication exposure (steroids and/or CNI). In regression analysis, male sex and urine protein:creatinine ratio (UPC) were significant determinants of hypertensive BP over time, while eGFR was found to be a determinant of dyslipidemia over time. CONCLUSIONS: Results demonstrate persistent hypertensive BPs and unfavorable lipid profiles in the cNEPTUNE cohort regardless of remission status or concurrent steroid or calcineurin inhibitor treatment.

Incidence, Risk Factors, and Outcomes Associated With Recurrent Neonatal Acute Kidney Injury in the AWAKEN Study.

Importance: The incidence and associated outcomes of recurrent acute kidney injury (rAKI) in neonates remain largely unknown. Objective: To determine the incidence, risk factors, and clinical outcomes associated with rAKI in critically ill neonates. Design, Setting, and Participants: This cohort study was a secondary analysis of the multicenter, international Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates retrospective study. Comparisons were made among neonates with no AKI, a single AKI episode (sAKI), and rAKI. All neonates younger than 14 days who were admitted between January 1 and March 31, 2014, to 24 participating level II to IV neonatal intensive care units and received intravenous fluids for at least 48 hours were considered for inclusion. Neonates with congenital heart disease requiring surgery within the first week of life, lethal chromosomal anomalies, death within 48 hours of admission, or severe congenital kidney abnormalities were excluded. Data were analyzed from May 23, 2022, to December 8, 2023. Exposure: Recurrent AKI using the neonatal Kidney Disease: Improving Global Outcomes criteria. Determination of each rAKI required a complete return to the baseline serum creatinine level that defined the prior AKI episode. Main Outcomes and Measures: Incidence and risk factors of rAKI and associations of rAKI with length of stay (LOS; ie, birth to hospital discharge) and mortality. Results: The study cohort (n = 2162) included 1233 male neonates (57.0%). Gestational age distribution was less than 29 weeks for 276 neonates (12.8%), 29 to less than 36 weeks for 958 (44.3%), and 36 weeks or older for 928 (42.9%). Of 605 neonates with AKI, 133 (22.0%) developed rAKI with risk factors including younger gestational age, lower birthweight, and higher stage of initial AKI. Infants with rAKI experienced longer median LOS (no AKI, 17 [IQR, 8-34] days; sAKI, 18 [IQR, 9-45] days; rAKI, 60 [IQR, 25-109] days; P < .001). Time-varying Cox proportional hazards regression models suggest rAKI is independently associated with a lower hazard of discharge (adjusted hazard ratio, 0.7 [95% CI, 0.6-0.9]; P = .01) when compared with sAKI, but mortality did not differ between groups (adjusted hazard ratio, 1.4 [95% CI, 0.6-3.0]; P = .44). Conclusions and Relevance: In this cohort study, neonatal rAKI was independently associated with longer LOS when compared with sAKI, suggesting that rAKI in neonates may be an important clinical distinction warranting further study and careful monitoring after an initial AKI episode.

Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults.

Importance: In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown. Objective: To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO; <10% vs ≥10%), is associated with major adverse kidney events at 90 days (MAKE-90). Design, Setting, and Participants: This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young adults (birth to 25 years) receiving CRRT for acute kidney injury or VO at 32 centers across 7 countries. Statistical analysis was performed from February to July 2023. Exposure: The primary exposure was time to CRRT initiation from intensive care unit admission. Main Outcomes and measures: The primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction [>25% decline in estimated glomerular filtration rate from baseline]). Results: Data from 996 patients were entered into the registry. After exclusions (n = 27), 969 patients (440 [45.4%] female; 16 (1.9%) American Indian or Alaska Native, 40 (4.7%) Asian or Pacific Islander, 127 (14.9%) Black, 652 (76.4%) White, 18 (2.1%) more than 1 race; median [IQR] patient age, 8.8 [1.7-15.0] years) with data for the primary outcome (MAKE-90) were included. Median (IQR) time to CRRT initiation was 2 (1-6) days. MAKE-90 occurred in 630 patients (65.0%), of which 368 (58.4%) died. Among the 601 patients who survived, 262 (43.6%) had persistent kidney dysfunction. Of patients with persistent dysfunction, 91 (34.7%) were dependent on dialysis. Time to CRRT initiation was approximately 1 day longer among those with MAKE-90 (median [IQR], 3 [1-8] days vs 2 [1-4] days; P = .002). 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, 1.03 [95% CI, 1.02-1.04]). Conclusions and Relevance: In this cohort study of children and young adults receiving CRRT, longer time to CRRT initiation was associated with greater risk of MAKE-90 outcomes, in particular, mortality. These findings suggest that prospective multicenter studies are needed to further delineate the appropriate time to initiate CRRT and the interaction between CRRT initiation timing and VO to continue to improve survival and reduce morbidity in this population.