Toward Equitable Kidney Function Estimation in Critical Care Practice: Guidance From the Society of Critical Care Medicine's Diversity, Equity, and Inclusion in Renal Clinical Practice Task Force.

OBJECTIVES: Accurate glomerular filtration rate (GFR) assessment is essential in critically ill patients. GFR is often estimated using creatinine-based equations, which require surrogates for muscle mass such as age and sex. Race has also been included in GFR equations, based on the assumption that Black individuals have genetically determined higher muscle mass. However, race-based GFR estimation has been questioned with the recognition that race is a poor surrogate for genetic ancestry, and racial health disparities are driven largely by socioeconomic factors. The American Society of Nephrology and the National Kidney Foundation (ASN/NKF) recommend widespread adoption of new "race-free" creatinine equations, and increased use of cystatin C as a race-agnostic GFR biomarker. DATA SOURCES: Literature review and expert consensus. STUDY SELECTION: English language publications evaluating GFR assessment and racial disparities. DATA EXTRACTION: We provide an overview of the ASN/NKF recommendations. We then apply an Implementation science methodology to identify facilitators and barriers to implementation of the ASN/NKF recommendations into critical care settings and identify evidence-based implementation strategies. Last, we highlight research priorities for advancing GFR estimation in critically ill patients. DATA SYNTHESIS: Implementation of the new creatinine-based GFR equation is facilitated by low cost and relative ease of incorporation into electronic health records. The key barrier to implementation is a lack of direct evidence in critically ill patients. Additional barriers to implementing cystatin C-based GFR estimation include higher cost and lack of test availability in most laboratories. Further, cystatin C concentrations are influenced by inflammation, which complicates interpretation. CONCLUSIONS: The lack of direct evidence in critically ill patients is a key barrier to broad implementation of newly developed "race-free" GFR equations. Additional research evaluating GFR equations in critically ill patients and novel approaches to dynamic kidney function estimation is required to advance equitable GFR assessment in this vulnerable population.

Programs and processes for advancing pediatric acute kidney support therapy in hospitalized and critically ill children: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

Pediatric acute kidney support therapy (paKST) programs aim to reliably provide safe, effective, and timely extracorporeal supportive care for acutely and critically ill pediatric patients with acute kidney injury (AKI), fluid and electrolyte derangements, and/or toxin accumulation with a goal of improving both hospital-based and lifelong outcomes. Little is known about optimal ways to configure paKST teams and programs, pediatric-specific aspects of delivering high-quality paKST, strategies for transitioning from acute continuous modes of paKST to facilitate rehabilitation, or providing effective short- and long-term follow-up. As part of the 26th Acute Disease Quality Initiative Conference, the first to focus on a pediatric population, we summarize here the current state of knowledge in paKST programs and technology, identify key knowledge gaps in the field, and propose a framework for current best practices and future research in paKST.

Pediatric AKI in the real world: changing outcomes through education and advocacy-a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

BACKGROUND: Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles education and advocacy play in the care of children with AKI, discuss the importance of customizing educational outreach efforts to individual groups and contexts, and highlight the opportunities created through innovations and partnerships to optimize lifelong health outcomes. METHODS: During the 26th Acute Disease Quality Initiative (ADQI) consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations on AKI research, education, practice, and advocacy in children. RESULTS: The consensus statements developed in response to three critical questions about the role of education and advocacy in pediatric AKI care are presented here along with a summary of available evidence and recommendations for both clinical care and research. CONCLUSIONS: These consensus statements emphasize that high-quality care for patients with AKI begins in the community with education and awareness campaigns to identify those at risk for AKI. Education is the key across all healthcare and non-healthcare settings to enhance early diagnosis and develop mitigation strategies, thereby improving outcomes for children with AKI. Strong advocacy efforts are essential for implementing these programs and building critical collaborations across all stakeholders and settings.

Altered amino acid profile in patients with SARS-CoV-2 infection.

Low plasma arginine bioavailability has been implicated in endothelial dysfunction and immune dysregulation. The role of arginine in COVID-19 is unknown, but could contribute to cellular damage if low. Our objective was to determine arginine bioavailability in adults and children with COVID-19 vs. healthy controls. We hypothesized that arginine bioavailability would be low in patients with COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We conducted a prospective observational study of three patient cohorts; arginine bioavailability was determined in asymptomatic healthy controls, adults hospitalized with COVID-19, and hospitalized children/adolescents <21 y old with COVID-19, MIS-C, or asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection identified on admission screen. Mean patient plasma amino acids were compared to controls using the Student's t test. Arginine-to-ornithine ratio, a biomarker of arginase activity, and global arginine bioavailability ratio (GABR, arginine/[ornithine+citrulline]) were assessed in all three groups. A total of 80 patients were included (28 controls, 32 adults with COVID-19, and 20 pediatric patients with COVID-19/MIS-C). Mean plasma arginine and arginine bioavailability ratios were lower among adult and pediatric patients with COVID-19/MIS-C compared to controls. There was no difference between arginine bioavailability in children with COVID-19 vs. MIS-C. Adults and children with COVID-19 and MIS-C in our cohort had low arginine bioavailability compared to healthy adult controls. This may contribute to immune dysregulation and endothelial dysfunction in COVID-19. Low arginine-to-ornithine ratio in patients with COVID-19 or MIS-C suggests an elevation of arginase activity. Further study is merited to explore the role of arginine dysregulation in COVID-19.

Impact of the Magnitude and Timing of Fluid Overload on Outcomes in Critically Ill Children: A Report From the Multicenter International Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) Study.

OBJECTIVES: With the recognition that fluid overload (FO) has a detrimental impact on critically ill children, the critical care nephrology community has focused on identifying clinically meaningful targets for intervention. The current study aims to evaluate the epidemiology and outcomes associated with FO in an international multicenter cohort of critically ill children. The current study also aims to evaluate the association of FO at predetermined clinically relevant thresholds and time points (FO ≥ 5% and FO ≥ 10% at the end of ICU days 1 and 2) with outcomes. DESIGN: Prospective cohort study. SETTING: Multicenter, international collaborative of 32 pediatric ICUs. PATIENTS: A total of 5,079 children and young adults admitted consecutively to pediatric ICUs as part of the Assessment of the Worldwide Acute Kidney Injury, Renal Angina and Epidemiology Study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The FO thresholds at the time points of interest occurred commonly in the cohort (FO ≥ 5%Day1 in 38.1% [ n = 1753], FO ≥ 10%Day1 in 11.7% [ n = 537], FO ≥ 5%Day2 in 53.3% [ n = 1,539], FO ≥ 10%Day2 in 25.1% [ n = 724]). On Day1, multivariable modeling demonstrated that FO ≥ 5% was associated with fewer ICU-free days, and FO ≥ 10% was associated with higher mortality and fewer ICU and ventilator-free days. On multivariable modeling, FO-peak, Day2 FO ≥ 5%, and Day2 FO ≥ 10% were associated with higher mortality and fewer ICU and ventilator-free days. CONCLUSIONS: This study found that mild-to-moderate FO as early as at the end of ICU Day1 is associated with adverse outcomes. The current study fills an important void in the literature by identifying critical combinations of FO timing and quantity associated with adverse outcomes (FO ≥ 5%Day1, FO ≥10%Day1, FO ≥ 5%Day2, and FO ≥ 10%Day2). Those novel findings will help guide the development of interventional strategies and trials targeting the treatment and prevention of clinically relevant FO.

External validation of the modified sepsis renal angina index for prediction of severe acute kidney injury in children with septic shock.

BACKGROUND: Acute kidney injury (AKI) occurs commonly in pediatric septic shock and increases morbidity and mortality. Early identification of high-risk patients can facilitate targeted intervention to improve outcomes. We previously modified the renal angina index (RAI), a validated AKI prediction tool, to improve specificity in this population (sRAI). Here, we prospectively assess sRAI performance in a separate cohort. METHODS: A secondary analysis of a prospective, multicenter, observational study of children with septic shock admitted to the pediatric intensive care unit from 1/2019 to 12/2022. The primary outcome was severe AKI (≥ KDIGO Stage 2) on Day 3 (D3 severe AKI), and we compared predictive performance of the sRAI (calculated on Day 1) to the original RAI and serum creatinine elevation above baseline (D1 SCr > Baseline +). Original renal angina fulfillment (RAI +) was defined as RAI ≥ 8; sepsis renal angina fulfillment (sRAI +) was defined as RAI ≥ 20 or RAI 8 to < 20 with platelets < 150 × 103/µL. RESULTS: Among 363 patients, 79 (22%) developed D3 severe AKI. One hundred forty (39%) were sRAI + , 195 (54%) RAI + , and 253 (70%) D1 SCr > Baseline + . Compared to sRAI-, sRAI + had higher risk of D3 severe AKI (RR 8.9, 95%CI 5-16, p < 0.001), kidney replacement therapy (KRT) (RR 18, 95%CI 6.6-49, p < 0.001), and mortality (RR 2.5, 95%CI 1.2-5.5, p = 0.013). sRAI predicted D3 severe AKI with an AUROC of 0.86 (95%CI 0.82-0.90), with greater specificity (74%) than D1 SCr > Baseline (36%) and RAI + (58%). On multivariable regression, sRAI + retained associations with D3 severe AKI (aOR 4.5, 95%CI 2.0-10.2, p < 0.001) and need for KRT (aOR 5.6, 95%CI 1.5-21.5, p = 0.01). CONCLUSIONS: Prediction of severe AKI in pediatric septic shock is important to improve outcomes, allocate resources, and inform enrollment in clinical trials examining potential disease-modifying therapies. The sRAI affords more accurate and specific prediction than context-free SCr elevation or the original RAI in this population.

Synergistic association of fluid overload and acute kidney injury on outcomes in pediatric cardiac ECMO: a retrospective analysis of the KIDMO database.

BACKGROUND: Acute kidney injury (AKI) and fluid overload (FO) are associated with poor outcomes in children receiving extracorporeal membrane oxygenation (ECMO). Our objective is to evaluate the impact of AKI and FO on pediatric patients receiving ECMO for cardiac pathology. METHODS: We performed a secondary analysis of the six-center Kidney Interventions During Extracorporeal Membrane Oxygenation (KIDMO) database, including only children who underwent ECMO for cardiac pathology. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria. FO was defined as < 10% (FO-) vs. ≥ 10% (FO +) and was evaluated at ECMO initiation, peak during ECMO, and ECMO discontinuation. Primary outcomes were mortality and length of stay (LOS). RESULTS: Data from 191 patients were included. Non-survivors (56%) were more likely to be FO + than survivors at peak ECMO fluid status and ECMO discontinuation. There was a significant interaction between AKI and FO. In the presence of AKI, the adjusted odds of mortality for FO + was 4.79 times greater than FO- (95% CI: 1.52-15.12, p = 0.01). In the presence of FO + , the adjusted odds of mortality for AKI + was 2.7 times higher than AKI- [95%CI: 1.10-6.60; p = 0.03]. Peak FO + was associated with a 55% adjusted relative increase in LOS [95%CI: 1.07-2.26, p = 0.02]. CONCLUSIONS: The association of peak FO + with mortality is present only in the presence of AKI + . Similarly, AKI + is associated with mortality only in the presence of peak FO + . FO + was associated with LOS. Studies targeting fluid management have the potential to improve LOS and mortality outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effect of a standardized fluid management algorithm on acute kidney injury and mortality in pediatric patients on extracorporeal support.

Acute kidney injury (AKI), fluid overload (FO), and mortality are common in pediatric patients supported by extracorporeal membrane oxygenation (ECMO). The aim of this study is to evaluate if using a fluid management algorithm reduced AKI and mortality in children supported by ECMO. We performed a retrospective study of pediatric patients aged birth to 25 years requiring ECMO at a quaternary level children's hospital from 2007 to 2019 In October 2017, a fluid management algorithm was implemented for protocolized fluid removal after deriving a daily fluid goal using a combination of diuretics and ultrafiltration. Daily algorithm compliance was defined as ≥ 12 h on the algorithm each day. The primary and secondary outcomes were AKI and mortality, respectively, and were assessed in the entire cohort and the sub-analysis of children from the era in which the algorithm was implemented. Two hundred and ninety-nine (median age 5.3 months; IQR: 0.2, 62.3; 45% male) children required ECMO (venoarterial in 85%). The fluid algorithm was applied in 74 patients. The overall AKI rate during ECMO was 38% (26% severe-stage 2/3). Both AKI incidence and mortality were significantly lower in patients managed on the algorithm (p = 0.02 and p = 0.05). After adjusting for confounders, utilization of the algorithm was associated with lower odds of AKI (aOR: 0.40, 95%CI: 0.21, 0.76; p = 0.005) but was not associated with a reduction in mortality. In the sub-analysis, algorithm compliance of 80-100% was associated with a 54% reduction in mortality (ref: < 60% compliant; aOR:0.46, 95%CI:0.22-1.00; p = 0.05).  Conclusion: Among the entire cohort, the use of a fluid management algorithm reduced the odds of AKI. Better compliance on the algorithm was associated with lower mortality. Multicenter studies that implement systematic fluid removal may represent an opportunity for improving ECMO-related outcomes. What is Known: • Acute kidney injury and fluid overload are associated with morbidity and mortality in children supported by extracorporeal membrane oxygenation. What is New: • A systematic and protocolized approach to fluid removal in children supported by extracorporeal membrane oxygenation reduces acute kidney injury incidence. • Greater adherence to a protocolized fluid removal algorithm is associated with a reduction in mortality.

Non-resuscitation fluid in excess of hydration requirements is associated with higher mortality in critically ill children.

BACKGROUND: Large volumes of non-resuscitation fluids are often administered to critically ill children. We hypothesize that excess maintenance fluid is a significant contributor to non-resuscitation fluid and that non-resuscitation fluid administered beyond hydration requirements is associated with worse clinical outcomes in critically ill children. METHODS: We evaluated all patients admitted to two large urban pediatric intensive care units (PICU) between January 2010-August 2016 and January 2010-August 2018, respectively, who survived and remained in the hospital for at least 3 days following PICU admission. The primary outcome was in-hospital mortality. Association of excess fluid with outcomes was adjusted for confounders (age, Pediatric Risk of Mortality III score, study site, day 3 acute kidney injury, PICU era, resuscitation volume, and volume output) using multivariable regression. RESULTS: We evaluated 14,483 patients; 52% received non-resuscitation fluid in excess of hydration requirements. Non-resuscitation fluid in excess of hydration requirements was associated with higher in-hospital mortality after adjustment for confounders (adjusted odds ratio 1.01 per 10 mL/kg in excess fluid, 95% confidence interval: 1.002-1.02). CONCLUSIONS: Non-resuscitation fluid in excess of hydration requirements is associated with increased mortality in critically ill children. Excess maintenance fluid is a modifiable contributor to this fluid volume. Strategies to reduce excess maintenance fluids warrant further study. IMPACT: Critically ill children frequently receive non-resuscitation fluid in excess of their estimated hydration requirements. Non-resuscitation fluid volume in excess of estimated hydration requirements is associated with higher morbidity and mortality in critically ill children. Critically ill children receive a large volume burden from maintenance fluid. Maintenance fluid represents a modifiable contributor of non-resuscitation fluid in excess of hydration requirements. Strategies focused on limitation of maintenance fluid warrant further study.

Acute kidney injury in critically Ill children and young adults with suspected SARS-CoV2 infection.

BACKGROUND: We aimed to study the association of suspected versus confirmed infection with the novel SARS-CoV2 virus with the prevalence of acute kidney injury (AKI) in critically ill children. METHODS: Sequential point-prevalence study of children and young adults aged 7 days to 25 years admitted to intensive care units under investigation for SARS-CoV2 infection. AKI was staged in the first 14 days of enrollment using KDIGO creatinine-based staging. SARS-CoV2 positive (CONFIRMED) were compared to SUSPECTED (negative or unknown). Outcome data was censored at 28-days. RESULTS: In 331 patients of both sexes, 179 (54.1%) were CONFIRMED, 4.2% (14) died. AKI occurred in 124 (37.5%) and severe AKI occurred in 63 (19.0%). Incidence of AKI in CONFIRMED was 74/179 (41.3%) versus 50/152 (32.9%) for SUSPECTED; severe AKI occurred in 35 (19.6%) of CONFIRMED and 28 (18.4%) of SUSPECTED. Mortality was 6.2% (n = 11) in CONFIRMED, but 9.5% (n = 7) in those CONFIRMED with AKI. On multivariable analysis, only Hispanic ethnicity (relative risk 0.5, 95% CI 0.3-0.9) was associated with less AKI development among those CONFIRMED. CONCLUSIONS: AKI and severe AKI occur commonly in critically ill children with SARS-CoV2 infection, more than double the historical standard. Further investigation is needed during this continuing pandemic to describe and refine the understanding of pediatric AKI epidemiology and outcomes. TRIAL REGISTRATION: NCT01987921. IMPACT: What is the key message of the article? AKI occurs in children exposed to the novel SARS-CoV2 virus at high prevalence (~40% with some form of AKI and 20% with severe AKI). What does it add to the existing literature? Acute kidney injury (AKI) occurs commonly in adult patients with SARS-CoV2 (COVID), very little data describes the epidemiology of AKI in children exposed to the virus. What is the impact? A pediatric vaccine is not available; thus, the pandemic is not over for children. Pediatricians will need to manage significant end-organ ramifications of the novel SARS-CoV2 virus including AKI.

Acute kidney injury in pediatric hematopoietic cell transplantation: critical appraisal and consensus.

Hematopoietic cell transplantation (HCT) is a common therapy for the treatment of neoplastic and metabolic disorders, hematological diseases, and fatal immunological deficiencies. HCT can be subcategorized as autologous or allogeneic, with each modality being associated with their own benefits, risks, and post-transplant complications. One of the most common complications includes acute kidney injury (AKI). However, diagnosing HCT patients with AKI early on remains quite difficult. Therefore, this evidence-based guideline, compiled by the Pediatric Continuous Renal Replacement Therapy (PCRRT) working group, presents the various factors that contribute to AKI and recommendations regarding optimization of therapy with minimal complications in HCT patients.

Transient and persistent acute kidney injury phenotypes following the Norwood operation: a retrospective study.

BACKGROUND: Acute kidney injury is a common complication following the Norwood operation. Most neonatal studies report acute kidney injury peaking within the first 48 hours after cardiac surgery. The aim of this study was to evaluate if persistent acute kidney injury (>48 postoperative hours) after the Norwood operation was associated with clinically relevant outcomes. METHODS: Two-centre retrospective study among neonates undergoing the Norwood operation. Acute kidney injury was initially identified as developing within the first 48 hours after cardiac surgery and stratified into transient (≤48 hours) and persistent (>48 hours) using the neonatal modification of the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Severe was defined as stage ≥2. Primary and secondary outcomes were mortality and duration of ventilation and hospital length of stay. RESULTS: One hundred sixty-eight patients were included. Transient and persistent acute kidney injuries occurred in 24 and 17%, respectively. Cardiopulmonary bypass and aortic cross clamp duration, and incidence of cardiac arrest were greater among those with persistent kidney injury. Mortality was four times higher (41 versus 12%, p < 0.001) and mechanical ventilation duration 50 hours longer in persistent acute kidney injury patients (158 versus 107 hours; p < 0.001). In multivariable analysis, persistent acute kidney injury was not associated with mortality, duration of ventilation or length of stay. Severe persistent acute kidney injury was associated with a 59% increase in expected ventilation duration (aIRR:1.59, 95% CI:1.16, 2.18; p = 0.004). CONCLUSIONS: Future large studies are needed to determine if risk factors and outcomes change by delineating acute kidney injury into discrete timing phenotypes.

Cumulative Application of Creatinine and Urine Output Staging Optimizes the Kidney Disease: Improving Global Outcomes Definition and Identifies Increased Mortality Risk in Hospitalized Patients With Acute Kidney Injury.

OBJECTIVES: Acute kidney injury is diagnosed according to creatinine and urine output criteria. Traditionally, both are applied, and a severity stage (1-3) is conferred based upon the more severe of the two; information from the other criteria is discarded. Physiologically, however, rising creatinine and oliguria represent two distinct types of renal dysfunction. We hypothesized that using the information from both criteria would more accurately characterize acute kidney injury severity and outcomes. DESIGN: Prospective cohort study. SETTING: Multicenter, international collaborative of ICUs. PATIENTS: Three thousand four hundred twenty-nine children and young adults admitted consecutively to ICUs as part of the Assessment of the Worldwide Acute Kidney Injury, Renal Angina and Epidemiology Study. MEASUREMENTS AND MAIN RESULTS: The Kidney Disease: Improving Global Outcomes creatinine and urine output acute kidney injury criteria were applied sequentially, and the two stages were summed, generating an Acute Kidney Injury (AKI) Score ranging from 1 to 6. The primary outcome was 28-day mortality; secondary outcomes were time until ICU discharge and nonrecovery from acute kidney injury. Models considered associations with AKI Score, assessing the relationship unadjusted and adjusted for covariates. Twenty-eight-day mortality and nonrecovery from acute kidney injury were modeled using logistic regression. For 28-day ICU discharge, competing risks analysis was performed. Although AKI Scores 1-3 had similar mortality to no Acute Kidney Injury, AKI Scores 4-6 were associated with increased mortality. Relative to No Acute Kidney Injury, AKI Scores 1-6 were less likely to be discharged from the ICU within 28 days. Relative to AKI Score 1, AKI Scores 2-6 were associated with higher risk of nonrecovery. Within the traditional Kidney Disease: Improving Global Outcomes Stage 3 acute kidney injury cohort, when compared with AKI Score 3, AKI Scores 4-6 had increased mortality, AKI Scores 5-6 had prolonged time to ICU discharge, and AKI Score 6 experienced higher nonrecovery rates. CONCLUSIONS: Cumulative application of the creatinine and urine output criteria characterizes renal excretory and fluid homeostatic dysfunction simultaneously. This Acute Kidney Injury score more comprehensively describes the outcome implications of severe acute kidney injury than traditional staging methods.

Clinical phenotypes of acute kidney injury are associated with unique outcomes in critically ill septic children.

BACKGROUND: Assessment of acute kidney injury (AKI) in septic patients remains imprecise. In adults, the classification of septic patients by clinical AKI phenotypes (severity and timing) demonstrates unique associations with patient outcome vs. broadly defined AKI. METHODS: In a multinational prospective observational study, AKI diagnosis in critically ill septic children was stratified by duration (transient vs. persistent) and severity (mild vs. severe by creatinine change and urine output). The outcomes of interest were mortality and intensive care unit resource complexity at 28 days. RESULTS: Seven hundred and fifty-seven septic children were studied (male 52.7%, age 4.6 years (1.5-11.9)). Mortality (overall 12.1%) was different between severe AKI and mild AKI (18.3 vs. 4.4%, p < 0.001) as well as intensive care unit (ICU) complexity (overall 34.5%, 45 vs. 21.7%, p < 0.001). Patients with Persistent AKI had fewer ICU-free days (17 (7, 21) vs. 24 (17, 26), p < 0.001) and higher ICU complexity (52.8 vs. 22.9%, p = 0.002) than transient AKI, even after exclusion of patients with early mortality. AKI phenotypes incorporating temporal and severity data correlate with unique survival (range 4.4-21.6%) and ICU-free days (range of 15-25 days) CONCLUSIONS: The outcome of septic children with AKI changes by clinical phenotype. Our findings underscore the importance of prognostic enrichment in sepsis and AKI for the purpose of trial design and patient management. IMPACT: Although AKI occurs commonly in patients with sepsis (S-AKI), outcomes for children with S-AKI varies based on the severity and timing of the AKI. Existing S-AKI pediatric data utilize a broad singular definition of kidney injury. Increasing the precision of AKI classification results in a new understanding of how S-AKI associates with patient outcome. A refined classification of S-AKI identifies subgroups of children, making possible a targeted and a personalized medicine approach to S-AKI study and management.

Controversies in paediatric acute kidney injury and continuous renal replacement therapy: can paediatric care lead the way to precision acute kidney injury medicine?

PURPOSE OF REVIEW: Paediatric patients represent a unique challenge for providers managing acute kidney injury (AKI). Critical care for these children requires a precise approach to assessment, diagnostics and management. RECENT FINDINGS: Primarily based on observational data, large epidemiologic datasets have demonstrated a strong association between AKI prevalence (one in four critically ill children) and poor patient outcome. Drivers of AKI itself are multifactorial and the causal links between AKI and host injury remain incompletely defined, creating a management paradigm primarily supportive in nature. The previous decades of research have focused primarily on elucidating the population-level epidemiologic signal of AKI and use of renal replacement therapy (RRT), but in order to reverse the course of the AKI 'epidemic', future decades will require more attention to the individual patient. A patient-level approach to AKI in children will require sophisticated approaches to risk stratification, diagnostics and targeted utilization of therapies (both supportive and targeted towards drivers of injury). SUMMARY: In this review, we will summarize the past, present and future of AKI care in children, discussing the ongoing work and future goals of a personalized approach to AKI medicine.

Severe acute respiratory syndrome coronavirus 2 infection and critically ill children.

PURPOSE OF REVIEW: Amidst an ongoing pandemic, the delineation of the pediatric consequence of infection from the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus is emerging. This review summarizes available pediatric data and covers the aspects of epidemiology, critical illness with acute infection [coronavirus disease 2019 (COVID-19)], the discovered multi-inflammatory syndrome in children (MIS-C), and management options. RECENT FINDINGS: The available data from the source of the initial viral transmission and then through Europe, Africa, and the Western Hemisphere identifies important aspects of the SARS-CoV2 pandemic: 1) Pediatric infection occurs commonly, is likely underestimated, and transmission patterns remain incompletely described, 2) Pediatric patients suffer multiple end-organ injuries but COVID-19 is not the same prevalence in terms of severity as in adults, 3) MIS-C is a novel and life-threatening manifestation of exposure to the virus, 4) Management using a combination of supportive care, standard practice intensive care management, and anti-inflammatory agents is associated with recovery, 5) Long-term sequelae of viral exposure is unknown at this time. SUMMARY: Emerging evidence suggests pediatric patients are at risk for severe and life-threatening effects of exposure to SARS-CoV2. As the pandemic continues, further research is warranted - particularly as a vaccine is not yet available for use in children.

Kidney support therapy in the pediatric patient: Unique considerations for a unique population.

The use of kidney support therapy (KST) for use in managing patients with acute kidney injury (AKI) has expanded greatly in the last several decades. The growing use of KST modalities in children, and now in neonates, has been associated with opportunities for education, clinical research, clinical practice improvements, and outcomes research. A multitude of controversies exist in the field of pediatric KST-many of which are shared by adult critical care nephrology practice. Simultaneously, pediatric KST has led the way to a burgeoning exploration of the importance of fluid overload as it relates to KST initiation and management and also with quality improvement. In this review, we will explore and describe the paradigms contained with pediatric KST used to support children with AKI. In addition to the governing principles related to the mechanics of KST, we will describe the novel aspects of newer support machines and ethical considerations of KST provision. Anticoagulation, dose, and modality will be discussed as well as priming procedures for special considerations. The utilization of KST across pediatric populations represents the next frontier of critical care nephrology.

Consensus acute kidney injury criteria integration identifies children at risk for long-term kidney dysfunction after multiple organ dysfunction syndrome.

BACKGROUND: The consensus definition of acute kidney injury (AKI) has evolved since developing the original multiple organ dysfunction syndrome (MODS) definitions. Whether or not risk for adverse short- and long-term outcomes can be identified using the refined AKI criteria in the setting of MODS has not been studied. We hypothesize that incorporation of Kidney Disease: Improving Global Outcome (KDIGO) AKI criteria into existing MODS definitions will have a higher association with major adverse kidney events at 30 days (MAKE30) and will increase the number of patients with MODS. METHODS: Post hoc analysis of 410 children admitted to a tertiary care pediatric intensive care unit (PICU) was conducted. MODS was defined using two existing criteria (Goldstein and Proulx) during the first 7 days following ICU admission and then modified by replacement of the kidney injury criteria using the KDIGO AKI definitions (G' and P'). RESULTS: MAKE30 occurred in 65 of 410 (16%) children. After substituting KDIGO kidney injury criteria, identification of MAKE30 increased from 46 children (71%) to 53 (82%) and 29 children (45%) to 43 (66%) for the Goldstein and Proulx criteria, respectively. Additionally, identification of MODS increased from 194 (47%) by Goldstein to 224 (55%) by G' and 95 children (23%) by Proulx to 132 (32%) by P'. CONCLUSIONS: Substituting KDIGO AKI criteria into existing MODS criteria increases the sensitivity for major adverse kidney events as well as the identification of MODS, improving the detection of children at risk for long-term adverse renal outcomes.

Timing of Fluid Overload and Association With Patient Outcome.

OBJECTIVES: To determine if the timing of excess fluid accumulation (fluid overload) is associated with adverse patient outcomes. DESIGN: Secondary analysis of a prospectively collected dataset. SETTING: PICU of a tertiary care hospital. PATIENTS: Children 3 months to 25 years old admitted to the PICU with expected length of stay greater than or equal to 48 hours. INTERVENTIONS: Patients were dichotomized by time of peak overload: peak fluid overload from ICU admission (Day0) to 48 hours (Day3-7) and peak fluid overload value after 48 hours of ICU admission, as well as time of first-time negative daily fluid balance: net fluid out greater than net fluid in for that 24-hour period. MEASUREMENTS AND MAIN RESULTS: There were 177 patients who met inclusion criteria, 92 (52%) male, with an overall mortality rate of 7% (n = 12). There were no differences in severity of illness scores or fluid overload on Day0 between peak fluid overload from ICU admission (Day0) to 48 hours (Day3-7) (n = 97; 55%) and peak fluid overload value after 48 hours of ICU admission (n = 80; 45%) groups. Peak fluid overload value after 48 hours of ICU admission was associated with a longer median ICU course (8 [4-15] vs 4 d [3-8 d]; p ≤ 0.001], hospital length of stay (18 [10-38) vs 12 [8-24]; p = 0.01], and increased risk of mortality (n = 10 [13%] vs 2 [2%]; χ2 = 7.6; p = 0.006]. ICU length of stay was also longer in the peak fluid overload value after 48 hours of ICU admission group when only patients with at least 7 days of ICU stay were analyzed (p = 0.02). Timing of negative fluid balance was also correlated with outcome. Compared with Day0-2, a negative daily fluid balance on Day3-7 was associated with increased length of mechanical ventilation (3 [1-7] vs 1 d [2-10 d]; p ≤ 0.001) and increased hospital (17 [10-35] vs 11 d [7-26 d]; p = 0.006) and ICU (7 [4-13] vs 4 d [3-7 d]; p ≤ 0.001) length of stay compared with a negative fluid balance between Day0-2. CONCLUSIONS: Our results show timing of fluid accumulation not just peak percentage accumulated is associated with patient outcome. Further exploration of the association between time and fluid accumulation is warranted.

Acute Kidney Injury, Fluid Overload, and Renal Replacement Therapy Differ by Underlying Diagnosis in Neonatal Extracorporeal Support and Impact Mortality Disparately.

INTRODUCTION: We aimed to characterize acute kidney injury (AKI), fluid overload (FO), and renal replacement therapy (RRT) utilization by diagnostic categories and examine associations between these complications and mortality by category. METHODS: To test our hypotheses, we conducted a retrospective multicenter, cohort study including 446 neonates (categories: 209 with cardiac disease, 114 with congenital diaphragmatic hernia [CDH], 123 with respiratory disease) requiring extracorporeal membrane oxygenation (ECMO) between January 1, 2007, and December 31, 2011. RESULTS: AKI, FO, and RRT each varied by diagnostic category. AKI and RRT receipt were most common in those neonates with cardiac disease. Subjects with CDH had highest peak %FO (51% vs. 28% cardiac vs. 32% respiratory; p < 0.01). Hospital survival was 55% and varied by diagnostic category (45% cardiac vs. 48% CDH vs. 79% respiratory; p < 0.001). A significant interaction suggested risk of mortality differed by diagnostic category in the presence or absence of AKI. In its absence, diagnosis of CDH (vs. respiratory disease) (OR 3.04, 95% CL 1.14-8.11) independently predicted mortality. In all categories, peak %FO (OR 1.20, 95% CL 1.11-1.30) and RRT receipt (OR 2.12, 95% CL 1.20-3.73) were independently associated with mortality. DISCUSSION/CONCLUSIONS: Physiologically distinct ECMO diagnoses warrant individualized treatment strategies given variable incidence and effects of AKI, FO, and RRT by category on mortality.