Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting.

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.

Long-term kidney outcomes in pediatric continuous-flow ventricular assist device patients.

BACKGROUND: Continuous-flow ventricular assist devices (CF-VADs) are used increasingly in pediatric end-stage heart failure (ESHF) patients. Alongside common risk factors like oxidant injury from hemolysis, non-pulsatile flow constitutes a unique circulatory stress on kidneys. Post-implantation recovery after acute kidney injury (AKI) is commonly reported, but long-term kidney outcomes or factors implicated in the evolution of chronic kidney disease (CKD) with prolonged CF-VAD support are unknown. METHODS: We studied ESHF patients supported > 90 days on CF-VAD from 2008 to 2018. The primary outcome was CKD (per Kidney Disease Improving Global Outcomes (KDIGO) criteria). Secondary outcomes included AKI incidence post-implantation and CKD evolution in the 6-12 months of CF-VAD support. RESULTS: We enrolled 134 patients; 84/134 (63%) were male, median age was 13 [IQR 9.9, 15.9] years, 72/134 (54%) had preexisting CKD at implantation, and 85/134 (63%) had AKI. At 3 months, of the 91/134 (68%) still on a CF-VAD, 34/91 (37%) never had CKD, 13/91 (14%) developed de novo CKD, while CKD persisted or worsened in 49% (44/91). Etiology of heart failure, extracorporeal membrane oxygenation use, duration of CF-VAD, AKI history, and kidney replacement therapy were not associated with different CKD outcomes. Mortality was higher in those with AKI or preexisting CKD. CONCLUSIONS: In the first multicenter study to focus on kidney outcomes for pediatric long-term CF-VAD patients, preimplantation CKD and peri-implantation AKI were common. Both de novo CKD and worsening CKD can happen on prolonged CF-VAD support. Proactive kidney function monitoring and targeted follow-up are important to optimize outcomes.

Fluid assessment, fluid balance, and fluid overload in sick children: a report from the Pediatric Acute Disease Quality Initiative (ADQI) conference.

BACKGROUND: The impact of disorders of fluid balance, including the pathologic state of fluid overload in sick children has become increasingly apparent. With this understanding, there has been a shift from application of absolute thresholds of fluid accumulation to an appreciation of the intricacies of fluid balance, including the impact of timing, trajectory, and disease pathophysiology. METHODS: The 26th Acute Disease Quality Initiative was the first to be exclusively dedicated to pediatric and neonatal acute kidney injury (pADQI). As part of the consensus panel, a multidisciplinary working group dedicated to fluid balance, fluid accumulation, and fluid overload was created. Through a search, review, and appraisal of the literature, summative consensus statements, along with identification of knowledge gaps and recommendations for clinical practice and research were developed. CONCLUSIONS: The 26th pADQI conference proposed harmonized terminology for fluid balance and for describing a pathologic state of fluid overload for clinical practice and research. Recommendations include that the terms daily fluid balance, cumulative fluid balance, and percent cumulative fluid balance be utilized to describe the fluid status of sick children. The term fluid overload is to be preserved for describing a pathologic state of positive fluid balance associated with adverse events. Several recommendations for research were proposed including focused validation of the definition of fluid balance, fluid overload, and proposed methodologic approaches and endpoints for clinical trials.

Advances in pediatric acute kidney injury pharmacology and nutrition: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

BACKGROUND: In the past decade, there have been substantial advances in our understanding of pediatric AKI. Despite this progress, large gaps remain in our understanding of pharmacology and nutritional therapy in pediatric AKI. METHODS: During the 26th Acute Disease Quality Initiative (ADQI) Consensus Conference, a multidisciplinary group of experts reviewed the evidence and used a modified Delphi process to achieve consensus on recommendations for gaps and advances in care for pharmacologic and nutritional management of pediatric AKI. The current evidence as well as gaps and opportunities were discussed, and recommendations were summarized. RESULTS: Two consensus statements were developed. (1) High-value, kidney-eliminated medications should be selected for a detailed characterization of their pharmacokinetics, pharmacodynamics, and pharmaco-"omics" in sick children across the developmental continuum. This will allow for the optimization of real-time modeling with the goal of improving patient care. Nephrotoxin stewardship will be identified as an organizational priority and supported with necessary resources and infrastructure. (2) Patient-centered outcomes (functional status, quality of life, and optimal growth and development) must drive targeted nutritional interventions to optimize short- and long-term nutrition. Measures of acute and chronic changes of anthropometrics, body composition, physical function, and metabolic control should be incorporated into nutritional assessments. CONCLUSIONS: Neonates and children have unique metabolic and growth parameters compared to adult patients. Strategic investments in multidisciplinary translational research efforts are required to fill the knowledge gaps in nutritional requirements and pharmacological best practices for children with or at risk for AKI.

Advances in pediatric acute kidney injury pathobiology: a report from the 26th Acute Disease Quality Initiative (ADQI) conference.

BACKGROUND: In the past decade, there have been substantial advances in our understanding of the pathobiology of pediatric acute kidney injury (AKI). In particular, animal models and studies focused on the relationship between kidney development, nephron number, and kidney health have identified a number of heterogeneous pathophysiologies underlying AKI. Despite this progress, gaps remain in our understanding of the pathobiology of pediatric AKI. 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 for opportunities to advance translational research in pediatric AKI. The current state of research understanding as well as gaps and opportunities for advancement in research was discussed, and recommendations were summarized. RESULTS: Consensus was reached that to improve translational pediatric AKI advancements, diverse teams spanning pre-clinical to epidemiological scientists must work in concert together and that results must be shared with the community we serve with patient involvement. Public and private research support and meaningful partnerships with adult research efforts are required. Particular focus is warranted to investigate the pediatric nuances of AKI, including the effect of development as a biological variable on AKI incidence, severity, and outcomes. CONCLUSIONS: Although AKI is common and associated with significant morbidity, the biologic basis of the disease spectrum throughout varying nephron developmental stages remains poorly understood. An incomplete understanding of factors contributing to kidney health, the diverse pathobiologies underlying AKI in children, and the historically siloed approach to research limit advances in the field. The recommendations outlined herein identify gaps and outline a strategic approach to advance the field of pediatric AKI via multidisciplinary translational research.

Fluid Overload Precedes and Masks Cryptic Kidney Injury in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: Given the complex interrelatedness of fluid overload (FO), creatinine, acute kidney injury (AKI), and clinical outcomes, the association of AKI with poor outcomes in critically ill children may be underestimated due to definitions used. We aimed to disentangle these temporal relationships in a large cohort of children with acute respiratory distress syndrome (ARDS). DESIGN: Retrospective cohort study. SETTING: Quaternary care PICU. PATIENTS: Seven hundred twenty intubated children with ARDS between 2011 and 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily fluid balance, urine output (UOP), and creatinine for days 1-7 of ARDS were retrospectively abstracted. A subset of patients had angiopoietin 2 (ANGPT2) quantified on days 1, 3, and 7. Patients were classified as AKI by Kidney Disease Improving Global Outcomes (KDIGO) stage 2/3 then grouped by timing of AKI onset (early if days 1-3 of ARDS, late if days 4-7 of ARDS, persistent if both) for comparison of PICU mortality and ventilator-free days (VFDs). A final category of "Cryptic AKI" was used to identify subjects who met KDIGO stage 2/3 criteria only when creatinine was adjusted for FO. Outcomes were compared between those who had Cryptic AKI identified by FO-adjusted creatinine versus those who had no AKI. Conventionally defined AKI occurred in 26% of patients (early 10%, late 3%, persistent 13%). AKI was associated with higher mortality and fewer VFDs, with no differences according to timing of onset. The Cryptic AKI group (6% of those labeled no AKI) had higher mortality and fewer VFDs than patients who did not meet AKI with FO-adjusted creatinine. FO, FO-adjusted creatinine, and ANGPT2 increased 1 day prior to meeting AKI criteria in the late AKI group. CONCLUSIONS: AKI was associated with higher mortality and fewer VFDs in pediatric ARDS, irrespective of timing. FO-adjusted creatinine captures a group of patients with Cryptic AKI with outcomes approaching those who meet AKI by traditional criteria. Increases in FO, FO-adjusted creatinine, and ANGPT2 occur prior to meeting conventional AKI criteria.

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.

Post-operative dysnatremia is associated with adverse early outcomes after surgery for congenital heart disease.

BACKGROUND: Dysnatremia is a common disorder in critically ill surgical children. The study's aim is to determine the prevalence of dysnatremia and its association with outcomes after surgery for congenital heart disease (CHD). METHODS: This is a single-center retrospective cohort study of children <18 years of age undergoing surgery for CHD between January 2012 and December 2014. Multivariable logistic regression analysis was used to evaluate the relationship between dysnatremia and outcomes during the perioperative period. A total of 1345 encounters met the inclusion criteria. RESULTS: The prevalence of pre- and post-operative dysnatremia were 10.2% and 47.1%, respectively. Hyponatremia occurred in 19.1%, hypernatremia in 25.6%. Hypernatremia at 24, 48, and 72 h post-operative was associated with increased hospital mortality (odds ratios (OR) [95% confidence intervals (CI)] 3.08 [1.16-8.17], p = 0.024; 4.35 [1.58-12], p = 0.0045; 4.14 [1.32-12.97], p = 0.0148, respectively. Hypernatremia was associated with adverse neurological events 3.39 [1.12-10.23], p = 0.0302 at 48 h post-operative. Hyponatremia was not associated with any adverse outcome in our secondary analysis. CONCLUSIONS: Post-operative dysnatremia is a common finding in this heterogeneous cohort of pediatric cardiac-surgical patients. Hypernatremia was more prevalent than hyponatremia and was associated with adverse early post-operative outcomes. IMPACT: Our study has shown that dysnatremia was highly prevalent in children after congenital heart surgery with hypernatremia associated with adverse outcomes including mortality. It is important to understand fluid and sodium regulation in the post-operative period in children with congenital heart disease to better address fluid overload and associated electrolyte imbalances and acute kidney injury. While clinicians are generally very aware of the importance of hyponatremia in critically ill children, similar attention should be given to hypernatremia in this population.

Quality of life after acute kidney injury.

PURPOSE OF REVIEW: Deciphering the effect of acute kidney injury (AKI) during critical illness on long-term quality of life versus the impact of conditions that brought on critical illness is difficult. RECENT FINDINGS: Reports on patient-centred outcomes such as health-related quality of life (HRQOL) have provided insight into the long-lasting impact of critical illness complicated by AKI. However, these data stem from observational studies and randomized controlled trials, which have been heterogeneous in their patient population, timing, instruments used for assessment and reporting. Recent studies have corroborated these findings including lack of effect of renal replacement therapy compared to severe AKI on outcomes and worse physical compared to cognitive dysfunction. SUMMARY: In adults, more deficits in physical than mental health domains are found in survivors of AKI in critical care, whereas memory deficits and learning impairments have been noted in children. Further study is needed to understand and develop interventions that preserve or enhance the quality of life for individual patients who survive AKI following critical illness, across all ages.

Current practices in pediatric continuous kidney replacement therapy: a systematic review-guided multinational modified Delphi consensus study.

BACKGROUND: Continuous kidney replacement therapy (CKRT) has become an integral part of the care of critically ill children. However, uncertainty exists regarding the current state of how CKRT is prescribed and delivered in children. The main objective of this study was to identify the current practices for pediatric CKRT. METHODS: We conducted a systematic review of the literature from 2012 to 2022 to identify data regarding CKRT timing of initiation, dosing, anticoagulation, fluid removal, and quality monitoring. Using this data, we then performed a two-round modified Delphi process using a multinational internet-assisted survey of prescribers of CKRT. RESULTS: The survey was constructed using 172 articles that met inclusion criteria (12% of studies were pediatric focused). A total of 147 and 126 practitioners completed the survey in rounds 1 and 2, respectively. Participants represented Europe (9.5-11.6%) and North America including pediatric intensivists, nephrologists, and advance practice providers. Consensus (defined as a ≥ 75% participant response of "sometimes" or "always") was achieved for 26 statements. There was consensus in the practices of CKRT initiation, dosing, method of anticoagulation, and fluid removal. In contrast, there appears to be greater variability in the methods used for monitoring anticoagulation and the quality of the delivered treatment. CONCLUSIONS: Our study results suggest that the current state of pediatric CKRT practice is reflective of the literature over the last 10 years, which is largely based on the care of adult patients. This data provides a framework to study best practices to further improve outcomes for children receiving CKRT. A higher resolution version of the Graphical abstract is available as Supplementary information.

Optimizing Vancomycin Dosing and Monitoring in Neonates and Infants Using Population Pharmacokinetic Modeling.

We determined optimal vancomycin starting dose regimens in infants ≤180 days of age to achieve the highest probability of target attainment with an area under the concentration-time curve for 24 h (AUC24) of ≥400 using population pharmacokinetic (PK) modeling. Secondarily, determination of the relationship between serum creatinine (SCR) and vancomycin clearance in neonates was done. A retrospective population PK study was designed and included pediatric patients ≤180 days old who had received vancomycin and had a serum vancomycin concentration sampled. A population PK model was developed using Pumas (v1.0.5). Simulation was performed with various dosing regimens to evaluate the probability of AUC24 target attainment and probability of trough of ≤20 mg/liter, and comparison to published models was performed. Individual clearance estimates, obtained from the final model, were plotted against SCR and faceted by age quartiles to assess the relationship between SCR and vancomycin clearance. A total of 934 patients were included in the study (58.6% male; median age, 43.6 days [range of 0 to 184]; median number of concentration samples, 1 [range of 1 to 29]). A one-compartment model was developed with body weight (WT), SCR, and postmenstrual age (PMA) identified as significant covariates on clearance. Plotting vancomycin clearance versus SCR demonstrated no clear relationship between the two at <10 days postnatal age (PNA). Dosing regimens to attain AUC24 and trough targets were stratified according to SCR for ≥10 days PNA and PMA for <10 days PNA. A vancomycin population PK model was developed for pediatric patients <180 days of age incorporating WT, SCR, and PMA. The relationship between vancomycin clearance and serum creatinine is not clear at <10 days PNA.

Postoperative physiological parameters associated with severe acute kidney injury after pediatric heart transplant.

BACKGROUND: The primary objective was to evaluate associations between perioperative clinical variables and postoperative hemodynamic indices after HT with the development of severe AKI. The secondary objective was to evaluate associations between UOP or creatinine as AKI indicators and morbidity after HT. METHODS: Retrospective study of all patients who underwent HT 1/2016-11/2019 at a quaternary pediatric institution. Severe AKI was defined as KDIGO stage 2 or higher. RESULTS: Of 94 HT patients, 73 met inclusion criteria; 45% of patients developed severe AKI. In univariate analysis, non-Hispanic Black race, preoperative AKI, longer CPB duration, lower weight, and peak lactate within 12 h post-HT were associated with severe AKI. CVP ≤12 h post-HT had a quadratic relationship, rather than linear, with severe AKI. PPV >18% was significantly associated with severe AKI but equated to noncontiguous 10 min of high variation over a 12-h period, and thus was deemed not clinically significant. In multivariate analysis, Black race, longer CPB duration, and higher CVP remained associated with severe AKI (c: 0.84, 95% CI 0.73-0.92). Severe AKI per creatinine, but not UOP criteria, was associated with longer duration of ventilation (p = .012) and longer intensive care unit length of stay (p = .003). CONCLUSIONS: In pediatric HT patients, non-Hispanic Black race, longer CPB time, and higher postoperative CVP ≤12 h post-HT were associated with severe AKI. AKI based on creatinine, not UOP, was associated with postoperative HT morbidity.

Hemodynamic instability during connection to continuous kidney replacement therapy in critically ill pediatric patients.

BACKGROUND: Emerging data suggest evidence of organ hypoperfusion during continuous kidney replacement therapy (CKRT). To facilitate kidney and global recovery, we must understand the hemodynamic risks associated with CKRT. We aimed to investigate frequency of hemodynamic instability and association with patient outcomes in pediatric CKRT. METHODS: In a single-center study of CKRT patients between September 2016 and October 2018, we collected hemodynamic data using archived high-resolution physiologic data before and after connection. Primary outcome was hypotension defined as ≥ 20% decrease in baseline mean arterial pressure (MAP) for ≥ 2 consecutive minutes in the 60 min following connection. Secondary outcomes were tachycardia (≥ 20% increase in heart rate (HR)) and hemodynamic interventions. RESULTS: Seventy-one patients median age 54 months (IQR 7-144), weight 16.7 kg (IQR 8-41), on hemodiafiltration had 304 filter connections, 4 (IQR 1-7) filters per patient; the median duration of CKRT was 9 days (IQR 3-20). The most common CKRT indication was AKI with fluid overload (48/71, 69%). There were 78 (27%) hypotension and 42 (14%) tachycardia events; cumulative duration of hypotension was 14 min IQR (3-31.75). Teams provided intervention in 17/304 (6%) of connections. Pediatric Logistic Organ Dysfunction 2 was the only independent predictor of hypotension (aOR 2.12 (CI 1.02-4.41)). CONCLUSIONS: One in four and one in six pediatric CKRT filter connections were complicated by hypotension and tachycardia, respectively. Higher illness severity at CKRT initiation was independently associated with hypotension. Impact of CKRT-associated hemodynamic instability on global patient outcomes requires further targeted study. A higher resolution version of the Graphical abstract is available as Supplementary information.

Patient-centered outcomes in pediatric continuous kidney replacement therapy: new morbidity and worsened functional status in survivors.

BACKGROUND: Ongoing measures to improve pediatric continuous kidney replacement therapy (CKRT) have lowered mortality rates, shifting the focus to survivor functional status. While septic acute kidney injury generates new morbidity in pediatric critically ill patients, acquired morbidities and functional status of CKRT population are unknown. We predicted that CKRT survivors are at risk for new morbidity and would have worse functional status at PICU discharge compared to baseline, and aimed to describe associated factors. METHODS: Retrospective cohort study over 24 months of CKRT patients surviving to PICU discharge in a quaternary children's hospital. Functional outcome was determined by Functional Status Scale (FSS). RESULTS: FSS scores were higher at PICU and hospital discharge compared to baseline. Of 45 CKRT survivors, 31 (69%) had worse FSS score at PICU discharge and 51% had new morbidity (≥3 increase in FSS); majority qualified as moderate to severe disability (FSS ≥10). Four patients (9%) had new tracheostomy, 3 (7%) were ventilator dependent, and 10 (22%) were dialysis dependent. Most (23/45, 51%) required outpatient rehabilitation. Cumulative days on sedation, controlled for illness severity, were independently associated with worse FSS at PICU discharge (aOR 25.18 (3.73, 169.92)). In adjusted analyses, duration of sedation was associated with new morbidity, while neurologic comorbidity, percent fluid overload at CKRT start, and nonrenal comorbidity were associated with moderate to severe disability at PICU discharge when controlled for baseline FSS. CONCLUSIONS: CKRT survivors, with new morbidity and worse functional outcomes at PICU discharge, are a newly described vulnerable population requiring targeted follow-up. Deliberate decrease of sedation exposure in patients with decreased clearance due to organ dysfunction needs to be studied as a modifiable risk factor.

The effect of continuous venovenous hemodiafiltration on amino acid delivery, clearance, and removal in children.

BACKGROUND: In critically ill children with acute kidney injury (AKI), continuous kidney replacement therapy (CKRT) enables nutrition provision. The magnitude of amino acid loss during continuous venovenous hemodiafiltration (CVVHDF) is unknown and needs accurate quantification. We investigated the mass removal and clearance of amino acids in pediatric CVVHDF. METHODS: This is a prospective observational cohort study of patients receiving CVVHDF from August 2014 to January 2016 in the pediatric intensive care unit (PICU) of a tertiary children's hospital. RESULTS: Fifteen patients (40% male, median age 2.0 (IQR 0.7, 8.0) years) were enrolled. Median PICU and hospital lengths of stay were 20 (9, 59) and 36 (22, 132) days, respectively. Overall survival to discharge was 66.7%. Median daily protein prescription was 2.00 (1.25, 2.80) g/kg/day. Median daily amino acid mass removal was 299.0 (174.9, 452.0) mg/kg body weight, and median daily amino acid mass clearance was 18.2 (13.5, 27.9) ml/min/m2, resulting in a median 14.6 (8.3, 26.7) % protein loss. The rate of amino acid loss increased with increasing dialysis dose and blood flow rate. CONCLUSION: CVVHDF prescription and related amino acid loss impact nutrition provision, with 14.6% of the prescribed protein removed. Current recommendations for protein provision for children requiring CVVHDF should be adjusted to compensate for circuit-related loss. A higher resolution version of the Graphical abstract is available as Supplementary information.

Preserved Cerebral Oxygenation with Worsening Global Myocardial Strain during Pediatric Chronic Hemodialysis.

BACKGROUND: Cerebral and myocardial hypoperfusion occur during hemodialysis in adults. Pediatric patients receiving chronic hemodialysis have fewer cardiovascular risk factors, yet cardiovascular morbidity remains prominent. METHODS: We conducted a prospective observational study of pediatric patients receiving chronic hemodialysis to investigate whether intermittent hemodialysis is associated with adverse end organ effects in the heart or with cerebral oxygenation (regional tissue oxyhemoglobin saturation [rSO2]). We assessed intradialytic cardiovascular function and rSO2 using noninvasive echocardiography to determine myocardial strain and continuous noninvasive near-infrared spectroscopy for rSO2. We measured changes in blood volume and measured central venous oxygen saturation (mCVO2) pre-, mid-, and post-hemodialysis. RESULTS: The study included 15 patients (median age, 12 years; median hemodialysis vintage, 13.2 [9-24] months). Patients were asymptomatic. The rSO2 did not change during hemodialysis, whereas mCVO2 decreased significantly, from 73% to 64.8%. Global longitudinal strain of the myocardium worsened significantly by mid-hemodialysis and persisted post-hemodialysis. The ejection fraction remained normal. Lower systolic BP and faster blood volume change were associated with worsening myocardial strain; only blood volume change was significant in multivariate analysis (ß-coefficient, -0.3; 95% confidence interval [CI], -0.38 to -0.21; P<0.001). Blood volume change was also associated with a significant decrease in mCVO2 (ß-coefficient, 0.42; 95% CI, 0.07 to 0.76; P=0.001). Access, age, hemodialysis vintage, and ultrafiltration volume were not associated with worsening strain. CONCLUSIONS: Unchanged rSO2 suggested that cerebral oxygenation was maintained during hemodialysis. However, despite maintained ejection fraction, intradialytic myocardial strain worsened in pediatric hemodialysis and was associated with blood volume change. The effect of hemodialysis on individual organ perfusion in pediatric versus adult patients receiving hemodialysis might differ.

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.

Kidney replacement therapy in pediatric patients on mechanical circulatory support: challenges for the pediatric nephrologist.

The use of mechanical circulatory support (MCS) therapies in children with medically refractory cardiac failure has increased over the past two decades. With the growing experience and expertise, MCS is currently offered as a bridge to recovery or heart transplantation and in some cases even as destination therapy. Acute kidney injury (AKI) is common in patients with end-stage heart failure (ESHF). When severe AKI develops requiring kidney replacement therapy (KRT), these patients present unique challenges for the pediatric nephrology team. The use of KRT has not been adequately described in children with ESHF on the newer MCS. We also present original case series data from our center experience. The purpose of this review is to familiarize the reader with the current MCS technologies, approach to their selection, how they interact when combined with current KRT circuits, and distinguish similarities and differences. We will attempt to highlight the distinctive features of each technology, specifically focusing on growing trends in use of continuous-flow ventricular assist devices (CF-VAD) as it poses additional challenges to the pediatric nephrologist.

Tandem plasmapheresis and continuous kidney replacement treatment in pediatric patients.

BACKGROUND: The objectives of the study are to describe tandem therapeutic plasma exchange (TPE) and continuous kidney replacement therapy (CKRT) patients' outcomes in a large institution. METHODS: We reviewed pediatric patients receiving tandem TPE and CKRT from 2013 to 2016. Over the study period, 63 discrete patients received tandem TPE and CKRT for a total of 378 TPE procedures on 1676 days on CKRT. RESULTS: Patient age ranged from newborn to 19 years old with weights ranging from 2.31 to 112.3 kg (17 patients were < 10 kg and less than 1 year old). All procedures were completed in intensive care units (ICU) as CKRT can only be done in this environment. All treatments completed successfully; majority of patients (90%) developed hypocalcemia though none were symptomatic. Case mortality rate was 40%. Disease severity scores at ICU admission were higher and time to TPE and CKRT start was longer in the deceased group. CONCLUSIONS: As a conclusion, though complications including hypocalcemia are common with tandem TPE and CKRT in pediatrics, patients remained asymptomatic. Such treatments have to be carefully planned with interdisciplinary teams to address indications, technicalities, and complications.

Clinical Consequences of Cardiomyopathy in Children With Biliary Atresia Requiring Liver Transplantation.

Cirrhotic cardiomyopathy (CCM), a comorbidity of end-stage cirrhotic liver disease, remains uncharacterized in children, largely because of a lack of an established pediatric definition. The aim of this retrospective cohort analysis is to derive objective two-dimensional echocardiographic (2DE) criteria to define CCM associated with biliary atresia (BA), or BA-CCM, and correlate presence of BA-CCM with liver transplant (LT) outcomes in this population. Using receiver operating characteristic (ROC) curve analysis, optimal cut-off values for left ventricular (LV) geometrical parameters that were highly sensitive and specific for the primary outcomes: A composite of serious adverse events (CSAE) and peritransplant death were determined. These results were used to propose a working definition for BA-CCM: (1) LV mass index (LVMI) ≥95 g/m2.7 or (2) relative wall thickness of LV ≥0.42. Applying these criteria, BA-CCM was found in 34 of 69 (49%) patients with BA listed for LT and was associated with increased multiorgan dysfunction, mechanical and vasopressor support, and longer intensive care unit (ICU) and hospital stays. BA-CCM was present in all 4 waitlist deaths, 7 posttransplant deaths, and 20 patients with a CSAE (P < 0.01). On multivariable regression analysis, BA-CCM remained independently associated with both death and a CSAE (P < 0.01). Utilizing ROC analysis, LVMI was found to be a stronger predictor for adverse outcomes compared with current well-established markers, including Pediatric End-Stage Liver Disease (PELD) score. Conclusion: BA-CCM is highly sensitive and specific for morbidity and mortality in children with BA listed for LT. 2DE screening for BA-CCM may provide pertinent clinical information for prioritization and optimal peritransplant management of these children.