Ayse Akcan-Arikan

Background Children with chronic kidney disease (CKD) often experience high levels of physical inactivity, exacerbating their health challenges and diminishing their quality of life. Given the potential health risks and reported barriers to sustained engagement in physical activity interventions, our objective was to evaluate the feasibility and acceptability of an individualized telehealth-supported physical activity program for adolescents with CKD stages 2–5. Methods This study was a 2-arm randomized waitlist control intervention to evaluate a 12-week telehealth physical activity program in children with CKD. Eligible participants, aged 11–18 years with CKD stages 2–5, were randomized via permuted block randomization, with CKD stage and sex as stratification factors, into a waitlist control (WLC) or physical activity intervention group. The treatment group received every 2-weeks video visits and personalized physical activity plans to increase or maintain ≥150 min of moderate to vigorous physical activity/week. All participants received a remotely tracked fitness wearable. Demographic and disease-based characteristics were collected at baseline to assess group differences. End-of-treatment surveys were conducted to assess acceptability, and inductive qualitative analysis was performed on two open-ended questions for both participant and guardian. Results Of 400 patients screened for eligibility, 37 were randomized (19 to waitlist control, 18 to treatment) with a recruitment rate of 4/month and an attrition rate of 2.7%. No demographic or disease characteristic differences were observed between groups. High fitness wearable adherence was observed in 35 participants. Median telehealth visit compliance was 83%. Qualitative analysis identified 3 categories: accountability and motivation (>30% citations from participants and parents relating to instructor motivation and accountability), the interplay of physical or mental health and physical activity (44% participant physical health), and personalization of the program to limit barriers to implementation (52% participant activity type, 44% participant education). Conclusion Telehealth-supported physical activity intervention is feasible in children with CKD with low attrition rates and high compliance to visits. Participants and guardians identified personalization and engagement strategies as central to their experience of the program, suggesting these may be important to intervention success.

Objectives: Literature in adults have demonstrated no differences in mortality based on the timing of renal replacement therapy (RRT) initiation. Pediatric studies have suggested that a longer duration between intensive care unit (ICU) admission and continuous RRT (CRRT) initiation is associated with worse outcomes. We aimed to investigate how the time between acute kidney injury (AKI) and CRRT initiation impacts outcomes in children, as this relationship remains uncertain. Methods: Retrospective cohort study of children (15% and CRRT initiation the likelihood of dialysis liberation decreased [HR 0.82 (CI: 0.72–0.93)]. Conclusions: Earlier CRRT initiation after AKI onset was associated with more RRT-free days, while AKI, defined by FO >15%, was associated with dialysis dependence. Our findings suggest that delaying CRRT in critically ill pediatric patients may lead to worse outcomes.

Hepatorenal syndrome (HRS-AKI) confers significant morbidity and mortality in patients with cirrhosis. Cirrhotic cardiomyopathy (CCM), a prevalent comorbidity in adults with growing recognition in children, leads to hemodynamic perturbations that may compound the maladaptive physiology resulting in HRS-AKI. We aimed to explore a hepato-cardio-renal link in pediatric cirrhosis by examining peritransplant AKI, with a focus on CCM and Major Adverse Kidney Events at 28 days (MAKE28) in patients undergoing liver transplant (LT). This is a single-center, retrospective study of pediatric LT for biliary atresia (BA) from 2014 to 2020. Peri-LT AKI was defined as AKI within 7 days of LT. CCM was defined as left ventricular mass index to height of ≥95 g/m ^2.7 , and/or relative wall thickness ≥0.42. Of 62 patients with BA (age 1.1 y [IQR: 0.8–2.4]), 29% had AKI, 61% had CCM, and 40% fulfilled MAKE28. Patients with AKI had higher blood product and vasoactive requirements, and lower ventilator-free days, compared with patients without AKI. The median length of stay was 133 (IQR: 54–121) versus 19.5 (IQR: 8.5–41) days for patients with AKI and without AKI, respectively ( p p =0.005). CCM remained significant after adjusting for age, markers of liver disease severity, and intraoperative events. Patients with BA face high morbidity peri-LT in the setting of prevalent AKI. The association between pediatric CCM and AKI suggests that cardiac dysfunction may be an independent risk factor for HRS-AKI. While studies are needed to further define the relationship between CCM and renal injury, pre-LT echocardiogram has the potential to facilitate timely identification and management of children at risk for HRS-AKI, and thereby promote renal recovery.

OBJECTIVES: Create systematic evidence maps of novel biomarkers of kidney injury from a mapping review to guide future implementation in patient care. DATA SOURCES: PubMed/MEDLINE and Embase. STUDY SELECTION: Systematic evidence maps included clinical trials and observational studies in critically ill patients, investigating novel kidney biomarkers for acute kidney injury (AKI). DATA EXTRACTION: Six thousand eight hundred five records were screened, and 1116 studies were included that related to one or more novel biomarkers and AKI. DATA SYNTHESIS: Adult populations accounted for 78.6% of the studies, and 93.3% used a cohort design to investigate AKI biomarkers. Mixed critically ill populations, cardiac surgery, and sepsis were identified as the most frequently studied clinical contexts in 69.5% of the studies. Systematic evidence maps were synthesized for biomarker studies to predict AKI ( n = 944), prognosticate clinical outcomes ( n = 647), diagnose AKI etiology ( n = 109), enrich clinical trials ( n = 6), and manage AKI ( n = 12). Implementation strategies for patient care included surveilling patients at risk of AKI, including patients undergoing surgery and those exposed to multiple nephrotoxic drugs. CONCLUSIONS: Substantial clinical evidence assessing the accuracy of biomarkers compared with diagnosis of AKI exists, with fewer practical trials in clinical use. Still, guidance on implementation approaches can be gleaned from evaluations using biomarkers for the management of critically ill patients, particularly in surgical and nephrotoxin-exposed populations where evidence is available. This review identifies the landscape of current evidence and highlights priorities for future management and enrichment trials needed to bridge the gap between predictive accuracy and clinical decision-making.

Scientific evidence regarding AKI and acute kidney care has advanced in recent years. However, a knowledge gap remains on the implementation of these evidence-based practices (EBPs) into clinical care. Implementation science (IS) is focused on ensuring that this knowledge is translated in an effective, efficient, and sustainable fashion. The objectives of this study were to ( 1 ) define the current status of IS; ( 2 ) define a roadmap for accelerating IS with a focus on patient/care partner advocacy, digital tool application, social determinants of health, and resource-limited settings; and ( 3 ) develop a robust and broad research agenda incorporating IS methodology into the programs. Acute Disease Quality Initiative XXXV was conducted through a modified Delphi process with virtual meetings preceding an in-person meeting. Five workgroups were determined a priori to focus on ( 1 ) IS definitions and methods applicable to AKI and acute kidney care; ( 2 ) IS literature in AKI and acute kidney care; ( 3 ) innovations in IS to accelerate the adoption, adherence to, and sustainment of EBPs in AKI and acute kidney care; ( 4 ) IS methods in resource-limited settings; and ( 5 ) recommendations to identify and evaluate EBPs that are ready for implementation or deimplementation. Before the in-person meeting, each workgroup met virtually to review the literature and develop framework questions to address their objectives. During the 2-day in person meeting, through iterative discussions, questions and supporting statements were finalized. These questions and statements were agreed upon through voting to achieve consensus, defined as agreement of ≥80%. We report a structured multidisciplinary consensus for defining the role of IS in AKI and acute kidney care. Future programs should address these consensus questions and apply these statements along with IS methodology in the translation of science into clinical practice and the implementation/deimplementation of EBPs in clinical care.

Key Points: Early trial of liberation from continuous renal replacement therapy was associated with improved patient-important clinical outcomes in children with preserved urine output. Hierarchical composite end point analysis demonstrated greater intensive care unit and hospital-free days among patients who underwent a liberation trial. These findings supported early assessment of readiness for liberation using urine output to guide decision making for children receiving continuous renal replacement therapy. Background: Data to guide assessment of readiness for liberation from continuous renal replacement therapy (CRRT) in children are limited, and hierarchical composite end points have not been applied in this setting. We evaluated whether performing a trial of CRRT liberation among patients with preserved urine output is associated with improved outcomes using a hierarchical end point approach. Methods: We conducted a retrospective cohort study of patients aged≤25 years from the multicenter Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease registry. Patients with urine output >0.5 ml/kg per hour for≥24 hours within the first 5 days after CRRT initiation were included. The primary exposure was a trial of CRRT liberation by day 5. The primary outcome was a hierarchical composite of: ( 1 ) 90-day mortality, ( 2 ) 90-day KRT dependence, ( 3 ) intensive care unit-free days, and ( 4 ) hospital-free days. Inverse probability weighting was used to balance baseline characteristics, and outcomes were compared using a win ratio analysis. Results: Among 366 eligible patients, 192 (53%) underwent a liberation trial by day 5. These patients were older, had higher reference serum creatinine levels, and exhibited lower illness severity when compared with those who did not undergo a trial of liberation. In adjusted analyses, a liberation trial was associated with an improved hierarchical outcome (win ratio, 2.14 [95% confidence interval, 1.56 to 2.94], P < 0.001), driven primarily by greater intensive care unit- and hospital-free days. Conclusion: Among CRRT recipients with preserved urine output, a trial of liberation by day 5 was associated with improved outcomes, supporting the early assessment of liberation readiness in patients with a urine output >0.5 ml/kg per hour.

Purpose : We investigated the prevalence of documented physical activity (PA) participation and recommendations among pediatric nephrologists and identified disease-related variables that predicted which patients received PA recommendations. Method : Patient charts were reviewed for children 3–18 years old, and data were extracted for those with international classification of disease 10 codes N18 (chronic kidney disease) or Z94.0 (kidney transplant). Demographic data, documented PA participation and recommendations, and disease variables were abstracted. Results : Of 404 patients (64% male; 12.4 [4.0]) with estimated glomerular filtration rate of 67.8 (30.9) mL/min/1.73 m ² ; 239 (59.2%) had documented PA participation, and 119 (29.6%) had a documented PA recommendation in their chart. PA recommendations were more likely in older patients (odds ratio [OR]: 1.08; 95% CI, 1.03–1.13), those with higher body mass index z score (OR: 1.45; 95% CI, 0.96–1.51), higher height z score (OR: 1.55; 95% CI, 1.31–1.82), higher estimated glomerular filtration rate (OR: 1.01; 95% CI, 1.01–1.02), sport participation (OR: 2.47; 95% CI, 1.46–4.19), and less likely for patients with higher motor score (OR: 0.6; 95% CI, 0.41–0.87; all P < .01). Adjusted analysis maintained significant associations except sports participation and motor score. Conclusion : A low proportion of children with chronic kidney disease, who are at risk of physical inactivity, received PA recommendations to increase PA. Recommendations were more likely in older, overweight, taller, better kidney function, and sport participants. Effect sizes were small or moderate; further study is needed.

Introduction: The selective cytopheretic device (SCD) is a cell-directed extracorporeal therapy approved for use in children with acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT) with sepsis/sepsis-like conditions. We compared outcomes for children treated with SCD to a contemporary cohort of children treated with CRRT alone. Methods: Secondary analysis and comparison of patients ≤22 years old and ≥10 kg from a multicenter registry of patients receiving CRRT for AKI and/or fluid overload (WE-ROCK; 2015–2021) to patients from two multicenter, prospective, interventional studies of children with AKI and multiple organ dysfunction (MODS) receiving SCD (SCD-PED-01/SCD-PED-02; 2016–2022). Results: Eighteen patients in the SCD cohort were compared to 178 in the CRRT cohort. There were no differences between cohorts at CRRT ± SCD initiation. SCD patients had shorter CRRT duration (6 [3, 11] vs. 10 [5, 18] days, p = 0.013) and shorter ICU length of stay (LOS) in survivors (16 [11, 25] vs. 27 [16, 46] days, p = 0.012). Survival to ICU discharge or day 60 was 94% in the SCD cohort vs. 74% in the CRRT cohort (p = 0.079). A Bayesian analysis demonstrated a >99% probability of improved survival with SCD. A sub-analysis in septic patients demonstrated greater survival (100% vs. 69%, p = 0.032), shorter CRRT duration (5 [3, 7] vs. 11 [6, 17] days, p = 0.006) and reduced ICU LOS in survivors (21 [10, 25] vs. 27 [16, 45] days, p = 0.027) in SCD-treated patients. Conclusions: The addition of SCD therapy in children with AKI and MODS receiving CRRT may be beneficial, though larger prospective studies are needed.

Background and hypothesis: Mortality rates of children supported with continuous renal replacement therapy (CRRT) have improved, yet morbidity remains high. We aimed to evaluate the functional outcomes of children receiving CRRT using Functional Status Scale (FSS). We hypothesized that children receiving CRRT will have worse FSS compared with their baseline and acquire new morbidity at hospital discharge and 6 and 12 months post-discharge, and that lack of renal recovery will contribute to worsening functional status. Methods: This is a retrospective chart review from The Worldwide Exploration of Renal Replacement Outcomes Collaborate in Kidney Disease (WE-ROCK), an international multi-center registry. Twenty-eight centers across five countries participated in this analysis. Children from birth to 25 years, on CRRT for acute kidney injury (AKI) or fluid overload, were included. Patients with underlying kidney disease, on extracorporeal membrane oxygenation and non-survivors were excluded. FSS was collected at discharge (n = 527), 6 months (n = 387) and 12 months post-discharge (n = 344). The primary outcome was FSS at discharge and 6 months. Secondary outcomes included: new morbidity at discharge and 6 months; FSS at 12 months; and the impact of renal recovery on functional outcomes. Results: A total of 527 patients had median FSS of 7 (6, 90) at hospital discharge. Thirty-nine percent (n = 204) had worse FSS. Eighteen percent (95/527) acquired a new morbidity at discharge. Predictors of FSS at discharge were baseline FSS {odds ratio (OR) 1.30 [95% confidence interval (CI) 1.11–1.52]}, weight [OR 0.99 (95% CI 0.98–0.9997)], comorbidities [OR 1.88 (95% CI 1.16–3.04)], mechanical ventilation [OR 1.72 (95% CI 1.04–2.85)] and sepsis on intensive care unit admission [OR 1.46 (95% CI 1.01–2.21)]. A total of 387 patients had median FSS score of 6 (6, 8) at 6 months. Ten percent (n = 39/387) acquired new morbidity at 6 months. The significant predictors of FSS at 6 months were FSS at discharge [OR 2.36 (95% CI 1.95–2.84)] and presence of comorbidities [OR 1.77 (95% CI 1.03–3.06)]. Conclusion: This is the first large, multi-center study evaluating functional outcomes of children on CRRT. Persistent morbidity following discharge emphasizes the importance of comprehensive identification and multidisciplinary follow-up to optimize patient outcomes.