Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. DESIGN: Retrospective cohort. SETTING: Two large quarternary care pediatric hospitals. PATIENTS: Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. CONCLUSIONS: Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

Utility of Cystatin C-based Equation for the Estimation of Glomerular Filtration Rate in a Pediatric Population.

BACKGROUND: The accurate assessment of kidney function is vital for the early detection of kidney damage. The estimated glomerular filtration rate GFR (eGFR) from serum cystatin C (CysC) and creatinine-based equations are commonly used in clinical practice as an alternative to the invasive measured glomerular filtration rate (mGFR), which is the usually accepted overall best index of kidney function in health and disease. Recently the CKiD under 25 (CkiD U25) equations have been shown to perform well in children and young adults with chronic kidney disease (CKD). In this focused report, we evaluated the performance of the CkiD U25 equations alongside 3 non-race-corrected (NRC) eGFR equations commonly used in pediatrics in our cohort. METHODS: mGFR measured following the intravenous injection of tracer Tc-99mDTPA was retrospectively compared with eGFR from these equations in 57 patients (6 months to 22 years) from different races/ethnicities. Ordinary least squares regression analyses were used to assess correlation between the mGFRs and eGFRs. RESULTS: The average mGFR for this cohort was 84.1 mL/min/1.73 m2. The NRC creatinine equations overestimated eGFR across all groups, with the lowest bias for CKiD U25-creatinine (22.59 mL/min/1.73 m2). The best correlations to mGFR, P30, and lowest biases were the CKiD U25-CysC (0.6281, 80.7%, 3.72 mL/min/1.73 m2) and Schwartz CysC (0.6372, 77.2%, -4.68 mL/min/1.73 m2). CONCLUSIONS: Overall, both CKiD U25-CysC and Schwartz CysC provide a good estimation of mGFR with the CKiD U25-CysC having the overall best performance compared to mGFR in our study.

Clearance and nutrition in neonatal continuous kidney replacement therapy using the Carpediem™ system.

BACKGROUND: Infants with kidney failure (KF) demonstrate poor growth partly due to obligate fluid and protein restrictions. Delivery of liberalized nutrition on continuous kidney replacement therapy (CKRT) is impacted by clinical instability, technical dialysis challenges, solute clearance, and nitrogen balance. We analyzed delivered nutrition and growth in infants receiving CKRT with the Cardio-Renal, Pediatric Dialysis Emergency Machine (Carpediem™). METHODS: Single-center observational study of infants receiving CKRT with the Carpediem™ between June 1 and December 31, 2021. We collected prospective circuit characteristics, delivered nutrition, anthropometric measurements, and illness severity Score for Neonatal Acute Physiology-II. As a surrogate to normalized protein catabolic rate in maintenance hemodialysis, we calculated normalized protein nitrogen appearance (nPNA) using the Randerson II continuous dialysis model. Descriptive statistics, Spearman correlation coefficient, Mann Whitney, Wilcoxon signed rank, receiver operating characteristic curves, and Kruskal-Wallis analysis were performed using SAS version 9.4. RESULTS: Eight infants received 31.9 (22.0, 49.7) days of CKRT using mostly (90%) regional citrate anticoagulation. Delivered nutritional volume, protein, total calories, enteral calories, nPNA, and nitrogen balance increased on CKRT. Using parenteral nutrition, 90 ml/kg/day should meet caloric and protein needs. Following initial weight loss of likely fluid overload, exploratory sensitivity analysis suggests weight gain occurred after 14 days of CKRT. Despite adequate nutritional delivery, goal weight (z-score = 0) and growth velocity were not achieved until 6 months after CKRT start. Most (5 infants, 62.5%) survived and transitioned to peritoneal dialysis (PD). CONCLUSIONS: Carpediem™ is a safe and efficacious bridge to PD in neonatal KF. Growth velocity of infants on CKRT appears delayed despite delivery of adequate calories and protein.

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.

Nutrition for critically ill children and neonates requiring dialysis: Application of clinical practice recommendations.

Approximately 30% of all children and neonates admitted to the intensive care unit (ICU) experience acute kidney injury (AKI). Children with AKI are largely poorly fed and experience high rates of malnutrition. Nutrition prescription and provision are exceptionally challenging for critically ill neonates, infants, and children with AKI given the dynamic nature of AKI and its respective treatment modalities. Managing the nutrition prescription of critically ill neonates, infants, and children with AKI requires nutrition support clinicians to have a high-level understanding of the various treatment modalities for AKI, which can affect the patient's protein, fluid, electrolyte, and mineral needs. Accurate and timely nutrition assessment in critically ill neonates and children with AKI can be flawed owing to difficulty obtaining accurate anthropometric parameters. Recently, the Pediatric Renal Nutrition Taskforce introduced clinical practice recommendations for the nutrition management of children with AKI. In this review, we will discuss the practical implications of these recent guidelines and work to bridge the knowledge and practice gaps for pediatric and neonatal nutrition support clinicians providing nutrition therapy for patients with AKI in the ICU. We also appraise special nutrition-related considerations for neonates with AKI given newer available renal replacement treatment modalities.

Apheresis medicine education during the early phase of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic introduced challenges and disruption across healthcare, including apheresis medicine (AM). In this study, we report findings from a survey conducted among American Society for Apheresis Physician Committee (ASFA-PC) members to describe the impact of the COVID-19 pandemic on AM education practices. STUDY DESIGN AND METHODS: A voluntary, anonymous, 24-question, institutional review board-approved survey regarding AM teaching during the pandemic was distributed to ASFA-PC members in the United States between December 1, 2020, and December 15, 2020. Descriptive analyses were reported as number and frequency of respondents for each question. Free text responses were summarized. RESULTS: Responses were received from 14/31 (45%) of ASFA-PC members, of whom 12 practiced at academic institutions. Among these, 11/12 (92%) transitioned to virtual platform for AM trainee conferences during the pandemic. A variety of resources were employed to support independent AM learning. While 7/12 (58%) respondents did not change the informed consent process for AM procedures, others delegated this process or introduced remote alternatives. The most common method respondents used to conduct AM patient rounding was a hybrid in-person/virtual model. CONCLUSION: This survey describes the adaptations and changes AM practitioners made to trainee education in response to the early phase of the COVID-19 pandemic. The transition to virtual and/or hybrid trainee learning and AM rounds underscores the importance of digital AM resources. Further study of the effects of the pandemic and its impact on AM trainee education, as well as patient care is warranted.

Cefepime Dosing in a Critically Ill Neonate Receiving Continuous Renal Replacement Therapy With the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM).

We report on a former 27-week gestational age infant who was placed on the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) at 4 months post-menstrual age while receiving cefepime treatment for an Enterobacter cloacae bacteremia and persistent peritonitis secondary to an infected peritoneal dialysis catheter. Using therapeutic drug monitoring while assessing the clearance of cefepime on continuous renal replacement therapy (CRRT), we were able to successfully treat this patient's infection while also minimizing the risk of side effects from this medication. Current literature supports dosing in adult patients on all modalities of CRRT with effluent flow rates of 20 to 25 mL/kg/hr; however, pharmacokinetic data on cefepime dosing in pediatric CRRT are scant. This case report describes the successful dosing strategy used for this patient while on various rates of continuous veno-venous hemodialysis with CARPEDIEM. Therapeutic drug monitoring of cefepime should be considered in critically ill pediatric patients on CARPEDIEM receiving CRRT.

Good outcomes for arteriovenous fistula with buttonhole cannulation for chronic hemodialysis in children and adolescents.

BACKGROUND: Arteriovenous fistula (AVF) is the preferred access for chronic hemodialysis (HD) in children and adolescents, but central venous catheter use is still high. METHODS: Retrospective chart review of children and adolescents with AVF created between January 2003 and December 2015 was performed to assess primary failure (PF), maturation time, functional primary and functional cumulative patency, and potential risk factors for AVF dysfunction. RESULTS: Ninety-nine AVF were created in 79 patients (54% male; 7-24 years; 16-147 kg) by experienced surgeons. Duplex ultrasonography vein mapping was used to assist with site selection. PF occurred in 17 AVF (17%) in 14 patients. Patient age, gender, ethnicity, underlying disease, time on dialysis, and AVF site were not associated with PF or patency. Coagulation abnormality was positively associated with PF (p = 0.03). Function was achieved in 82 AVF (83%) in 77 patients (97%). Median maturation time was 83 days (range 32-271). AVF were accessed via buttonholes. Functional primary patency was 95%, 84%, and 53% at 1, 2, and 5 years. Overall 1- and 2-year functional cumulative patency was 95%, but lower for small patients 16-30 kg (88%) and those greater than 80 kg (91%). The 5-year patency rate was 80%, but significantly lower for 16-30 kg (59%) and greater than 80 kg (55%). Risk analysis showed significantly better patency for 31-45 kg and 46-80 kg groups (p < 0.01), non-obese BMI (p = 0.01), and buttonhole self-cannulation (p = 0.03). CONCLUSIONS: This study provides more information about successful AVF with buttonhole cannulation in pediatric hemodialysis patients lending additional support for AVF use in pediatrics. A higher resolution version of the Graphical abstract is available as Supplementary information.

A modified Kidney Donor Risk Index for pediatric kidney transplant recipients.

BACKGROUND: The Kidney Donor Risk Index (KDRI) by Rao et al. was developed to measure the quality of kidney allografts. While Rao's KDRI has been found to be a robust measure of kidney allograft survival for adult kidney transplant recipients, many studies have indicated the need to create a distinct pediatric KDRI. METHODS: Our retrospective study utilized data from the United Network for Organ Sharing database. We examined 9295 deceased donor recipients' data for age < 18 years from 1990 to 2020. We performed a multivariate Cox regression to determine the significant recipient and transplant factors impacting pediatric kidney allograft survival. RESULTS: Multivariate analysis found 5 donor factors to be independently associated with graft failure or recipient death: age, female sex, anoxia as the cause of death, history of cigarette use, and cold ischemia time. Using receiver operator characteristic (ROC) curve analysis and analyzing the predictive value of each KDRI at 1, 5, and 10 years, the proposed pediatric KDRI had a statistically significant and higher predictive value for pediatric recipients at 5 (0.60 versus 0.57) and 10 years (0.61 versus 0.57) than the Rao KDRI. CONCLUSIONS: The proposed pediatric KDRI may provide a more accurate and simpler index to assess the quality of kidney allografts for pediatric recipients. However, due to the mild increase in predictive capabilities over the Rao index, the study serves as a proof of concept to develop a pediatric KDRI. Further studies should focus on increasing the index's predictive capabilities. A higher resolution version of the Graphical abstract is available as Supplementary information.

Relation of Low Chloride Concentration to Diuretic Efficiency and Transplant-Free Survival in Children Hospitalized With Heart Failure.

Serum chloride plays an important role in fluid homeostasis and is associated with impaired diuretic responsiveness and mortality in adults with heart failure (HF). We sought to characterize the relationship of serum chloride and diuretic efficiency (DE) and to determine its prognostic importance in children hospitalized with acute decompensated HF (ADHF). We studied DE, defined as net fluid output/kg+constant per mg of loop diuretic/kg, in 200 children hospitalized with ADHF. Median serum chloride at admission was 102 mmol/L (interquartile range 99 to 105 mmol/L), and hypochloremia (chloride ≤96 mmol/L) was present in 16% of the population at admission. Serum chloride correlated with serum sodium (r = 0.66; p < 0.001) and bicarbonate (r = -0.39; p < 0.001). In the adjusted analysis, lower chloride was associated with reduced DE (p < 0.001). Serum sodium was associated with DE on the unadjusted analysis; however, the association was eliminated when added to the model with chloride (p = 0.442). Lower chloride was also associated with features of inadequate decongestion during hospitalization: a positive fluid balance (p = 0.003), greater cumulative loop diuretic dose per weight (p = 0.001), addition of a thiazide diuretic during hospitalization (p < 0.001), less weight loss (p = 0.025), and longer length of stay (p = 0.003). Chloride concentration was independently associated with death or transplant 1 year after admission (hazard ratio 0.94; p < 0.001). As a dichotomous variable, hypochloremia was independently associated with reduced DE (p < 0.001) and decreased 1-year transplant-free survival (hazard ratio 2.3, p < 0.001). Lower serum chloride at hospital admission is strongly and independently associated with impaired DE and reduced transplant-free survival in children hospitalized with ADHF.

Good outcomes after pediatric intraperitoneal kidney transplant.

BACKGROUND: Kidney transplantation in small children is technically challenging. Consideration of whether to use intraperitoneal versus extraperitoneal placement of the graft depends on patient size, clinical history, anatomy, and surgical preference. We report a large single-center experience of intraperitoneal kidney transplantation and their outcomes. METHODS: We conducted a retrospective review of pediatric patients who underwent kidney transplantation from April 2011 to March 2018 at a single large volume center. We identified those with intraperitoneal placement and assessed their outcomes, including graft and patient survival, rejection episodes, and surgical or non-surgical complications. RESULTS: Forty-six of 168 pediatric kidney transplants (27%) were placed intraperitoneally in children mean age 5.5 ± 2.3 years (range 1.6-10 years) with median body weight 18.2 ± 5 kg (range 11.4-28.6 kg) during the study period. Two patients (4%) had vascular complications; 10 (22%) had urologic complications requiring intervention; all retained graft function. Thirteen patients (28%) had prolonged post-operative ileus. Eight (17%) patients had rejection episodes ≤6 months post-transplant. Only one case resulted in graft loss and was associated with recurrent focal segmental glomerular sclerosis (FSGS). Two patients (4%) had chronic rejection and subsequent graft loss by 5-year follow-up. At 7-year follow-up, graft survival was 93% and patient survival was 98%. CONCLUSIONS: The intraperitoneal approach offers access to the great vessels, which allows greater inflow and outflow and more abdominal capacity for an adult donor kidney, which is beneficial in very small patients. Risk of graft failure and surgical complications were not increased when compared to other published data on pediatric kidney transplants.

A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial.

Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production-dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use as an enteral phosphate binder and iron replacement product in adults with CKD. Clinical trials in adult CKD cohorts have also demonstrated that ferric citrate decreases circulating FGF23 concentrations. This review outlines the possible deleterious effects of excess FGF23 in CKD, summarizes data from the adult CKD clinical trials of ferric citrate, and presents the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) study, a randomized, placebo-controlled trial to evaluate the effects of ferric citrate on FGF23 in pediatric patients with CKD stages 3-4 (ClinicalTrials.gov Identifier NCT04741646).

Necrotizing enterovirus myositis in a pediatric renal transplant recipient.

BACKGROUND: Enteroviruses can cause severe infections, including viral myocarditis, meningitis, acute flaccid myelitis, and viral myositis. METHODS/RESULTS: We report a 3-year-old female renal transplant recipient who presented to a tertiary care hospital with elevated serum liver aminotransferases and subsequently developed proximal muscle pain, weakness, and respiratory distress during the first week of hospitalization. Imaging of the lower extremities revealed diffuse myositis of the proximal thigh and pelvic muscles. A muscle biopsy was obtained and revealed necrotizing myositis with immunostaining positive for enterovirus, consistent with a diagnosis of enterovirus necrotizing myositis. She had complete resolution of symptoms with steroids, intravenous immune globulin, reduced tacrolimus dose, and physical therapy. CONCLUSIONS: Enterovirus myositis should be included in the differential diagnosis for necrotizing myositis following renal transplantation in children.

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.

Role of therapeutic apheresis in the treatment of pediatric kidney diseases.

Therapeutic apheresis utilizes apheresis procedures in the treatment of a variety of conditions including kidney disease. Therapeutic plasma exchange (TPE) is the most common modality employed with the rationale of rapid reduction of a pathogenic substance distributed primarily in the intravascular compartment; however other techniques which adsorb such pathogenic substances or alter the immune profile have been utilized in diseases affecting native and transplanted kidneys. This article discusses the modalities and technical details of therapeutic apheresis and summarizes its role in individual diseases affecting the kidney. Complications related to pediatric apheresis procedures and specifically related to apheresis in kidney disease are also discussed. Though therapeutic apheresis modalities are employed frequently in children with kidney disease, most experiences are extrapolated from adult studies. International and national registries need to be established to elucidate the role of apheresis modalities in children with kidney disease.

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.

Left ventricular strain and left atrial strain are impaired during hemodialysis in children.

We aimed to investigate intradialytic changes in ventricular and atrial function using speckle tracking echocardiography (STE) in pediatric hemodialysis (HD). Children with HD vintage > 3 months were enrolled, and echocardiography was performed prior to, during, and after HD. STE was analyzed using GE EchoPAC. Left ventricular (LV) global longitudinal strain (GLS), strain rate (Sr), and mechanical dispersion index (MDI) were calculated as the average from 3 apical views; diastolic strain (Ds) and Sr from 4-chamber tracing; left atrial strain (LAS) and Sr from the 4- and 2-chamber views. A total of 15 patients were enrolled at a median age of 12 years (IQR 8, 16) and median HD vintage of 13 months (IQR 9, 25). GLS worsened during HD (- 15.8 ± 2.2% vs - 19.9 ± 1.9%, p < 0.001). Post-HD GLS was associated with BP decrease (coefficient = 0.62, p = 0.01). LV MDI and systolic Sr did not change. LV Ds progressively worsened (- 8.4% (- 9.2, - 8.0) vs - 11.9% (- 13.4, - 10.3), p < 0.001). LAS changes at mid-HD returned to baseline post-HD. Ds, DSr, LAS, LASr were not associated with BV removal or BP decrease (p > 0.1). In conclusions, intradialytic LV strain and LAS changes consistent with subclinical systolic and diastolic dysfunction were observed during HD in children. Changes in Ds, DSr, LAS, and LASr were not associated with BP change or BV removal and may be related to the disease progression. Longitudinal study using these novel indices may unfold the effect of these subclinical changes on long-term cardiovascular health in children requiring chronic HD.

Factors associated with long-term graft survival in pediatric kidney transplant recipients.

Pediatric kidney transplant recipients generally have good outcomes post-transplantation. However, the younger age and longer life span after transplantation in the pediatric population make understanding the multifactorial nature of long-term graft survival critical. This investigation analyzes factors associated with 10-year survival to identify areas for improvement in patient care. Kaplan-Meier with log-rank test and univariable and multivariable logistic regression methods were used to retrospectively analyze 7785 kidney transplant recipients under the age of 18 years from January 1, 1998, until March 9, 2008, using United Network for Organ Sharing (UNOS) data. Our end-point was death-censored 10-year graft survival after excluding recipients whose grafts failed within one year of transplant. Recipients aged 5-18 years had lower 10-year graft survival, which worsened as age increased: 5-9 years (OR: 0.66; CI: 0.52-0.83), 10-14 years (OR: 0.43; CI: 0.33-0.55), and 15-18 years (OR: 0.34; CI: 0.26-0.44). Recipient African American ethnicity (OR: 0.67; CI: 0.58-0.78) and Hispanic donor ethnicity (OR: 0.82; CI: 0.72-0.94) had worse outcomes than other donor and recipient ethnicities, as did patients on dialysis at the time of transplant (OR: 0.82; CI: 0.73-0.91). Recipient private insurance status (OR: 1.35; CI: 1.22-1.50) was protective for 10-year graft survival. By establishing the role of age, race, and insurance status on long-term graft survival, we hope to guide clinicians in identifying patients at high risk for graft failure. This study highlights the need for increased allocation of resources and medical care to reduce the disparity in outcomes for certain patient populations.

Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults.

Importance: Rituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children. Objective: To describe the use of rituximab and to assess whether its use is associated with short- or long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. Design, Setting, and Participants: This retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020. Exposure: One or more doses of rituximab. Main Outcomes and Measures: Adverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events. Results: We identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19+ or CD20+ cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-for-age B cell counts. Recovery of CD27+ memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM. Conclusions and Relevance: Rituximab is well tolerated among young people and is associated with few serious adverse events, but infections are common, corresponding to a prolonged period of B cell count recovery often lasting for longer than a year. Further examination of strategies to prevent infections following rituximab should be pursued.