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Plant-based diets are growing in popularity worldwide due to the importance of reducing the population's ecological footprint as well as an emerging role in the prevention and treatment of chronic human diseases. In adults, plant-based diets have been shown to be beneficial for preventing and controlling conditions that are common in patients with chronic kidney disease (CKD), such as obesity, hypertension, type 2 diabetes, dyslipidemia, and metabolic acidosis. Emerging evidence suggests that the higher fiber content of plant-based diets may help to modulate production of uremic toxins through beneficial shifts in the gut microbiome. The effects of the plant-based diet on progression of CKD remain controversial, and there are no data to support this in children. However, knowledge that the bioavailability of potassium and phosphorus from plant-based foods is reduced has led to recent changes in international kidney-friendly diet recommendations for children with CKD. The new guidelines advise that high potassium fruits and vegetables should no longer be automatically excluded from the kidney-friendly diet. In fact, a plant-based diet can be safely implemented in children with CKD through building the diet around whole, high fiber foods, avoiding processed foods and using recommended cooking methods to control potassium. The health benefits of the plant-based diet compared to omnivorous diets in children with CKD need investigation., Author(s): Jennifer Nhan [sup.1] , Kristen Sgambat [sup.1] , Asha Moudgil [sup.1] Author Affiliations: (1) grid.239560.b, 0000 0004 0482 1586, Department of Nephrology, Children's National Hospital, , 111 Michigan Avenue [...]

Background Children with kidney failure have increased risk for cardiovascular morbidities before and after transplantation. Ejection fraction is often preserved, masking cardiac dysfunction until severe. Data on longitudinal changes in diastolic function and cardiac geometry are limited. Methods A prospective study was conducted to investigate longitudinal changes in diastolic function and structure pre- and post-kidney transplant compared with healthy peers. Transplant recipients (n = 41) had echocardiograms pre-transplant, 1, 18, 30, and 42 months post-transplant. The controls (n = 26) underwent one echocardiogram. Diastolic function and cardiac geometry were assessed by E/e' lateral, E/A, interventricular septal end diastole diameter, left ventricular internal end diastole diameter, left ventricular posterior wall end diastole diameter, and left atrial dimension. Results E/e' of patients remained worse than controls until 30 months post-transplant, and E/A was impaired at all time points compared to the controls. Left ventricular geometry was abnormal in 46% pre-transplant and remained altered in 44.7%, 32.3%, 30.7%, and 27.2% at 1, 18, 30, and 42 months post-transplant. Determinants of diastolic dysfunction included hemodialysis, uncontrolled hypertension, steroid exposure, and metabolic syndrome; abnormal geometry was associated with glomerular diagnosis, dialysis duration, obesity, steroids, and metabolic syndrome. Abnormal diastolic function and structure were associated with left ventricular hypertrophy. Conclusion Diastolic dysfunction and geometry partially improve after transplant but remain abnormal in a subset of patients compared to healthy peers. Traditional indicators of systolic function are preserved. Modifiable risk factors include dialysis modality and duration, uncontrolled hypertension, corticosteroids, obesity, and metabolic syndrome. Attention to diastolic changes provides opportunity for early intervention. Graphical abstract, Author(s): Kristen Sgambat [sup.1] , Sarah Clauss [sup.2] , Asha Moudgil [sup.1] Author Affiliations: (1) grid.239560.b, 0000 0004 0482 1586, Nephrology, Children's National Hospital, , 111 Michigan Avenue NW, 20010, [...]

Belatacept is an intravenously infused selective T cell costimulation blocker approved for preventing organ rejection in renal transplant recipients aged ≥18 years. This phase I trial examined the pharmacokinetics and pharmacodynamics (percentage CD86 receptor occupancy [%CD86RO]) of a single dose of belatacept (7.5 mg/kg) administered to kidney transplant recipients aged 12-17 years receiving a stable calcineurin inhibitor-based immunosuppressive regimen. Nine adolescents (mean age 15.1 years) who were seropositive for Epstein-Barr virus were enrolled; all completed the 6-month study. Pharmacokinetics suggested relatively low variability of exposure (coefficients of variation for maximum observed serum concentration [Cmax ] and area under the serum concentration-time curve from time zero extrapolated to infinity [AUC0-INF ] were 20% and 25%, respectively). Mean half-life (T1/2 ) occurred 7.2 days postinfusion. Belatacept total body clearance was 0.48 mL/h/kg, and volume of distribution at steady-state (Vss ) was low at 0.09 L/kg. Compared with historical data from healthy adult volunteers administered a single dose of belatacept 10 mg/kg and adult kidney transplant recipients administered multiple doses of belatacept 5 mg/kg, pharmacokinetic values for adolescents were similar, indicating consistency across adolescent and adult populations. Mean %CD86RO increased with increasing belatacept concentration, indicating a direct relationship between pharmacokinetics and pharmacodynamics. Four patients reported 7 serious adverse events; none was considered related to belatacept. These data will inform belatacept dose selection in future studies of adolescent kidney transplant recipients.

Background Carnitine plays a key role in energy production in the myocardium and is efficiently removed by continuous kidney replacement therapy (CKRT). Effects of levocarnitine supplementation on myocardial function in children receiving CKRT have not been investigated. Methods This controlled pilot cohort study of 48 children investigated effects of levocarnitine supplementation on myocardial strain in children receiving CKRT for acute kidney injury (AKI). Children (n = 9) with AKI had total (TC) and free plasma carnitine (FC) measurements and echocardiogram for longitudinal and circumferential strain at baseline (prior to CKRT) and follow-up (on CKRT for 1 week with intravenous levocarnitine supplementation, 20 mg/kg/day). Intervention group was compared with three controls: (1) CKRT controls (n = 10) received CKRT 1 week (+AKI, no levocarnitine), (2) ICU controls (n = 9) were parenteral nutrition-dependent for 1 week (no AKI, no levocarnitine), and (3) healthy controls (n = 20). Results In the Intervention group, TC and FC increased from 36.0 and 18 [mu]mol/L to 93.5 and 74.5 [mu]mol/L after supplementation. TC and FC of unsupplemented CKRT controls declined from 27.2 and 18.6 [mu]mol/L to 12.4 and 6.6 [mu]mol/L, which was lower vs. ICU controls (TC 32.0, FC 26.0 [mu]mol/L), p < 0.05. Longitudinal and circumferential strain of the Intervention group improved from - 18.5% and - 18.3% to - 21.1% and - 27.6% after levocarnitine supplementation; strain of CKRT controls (-14.4%, -20%) remained impaired and was lower vs. Intervention and Healthy Control groups at follow-up, p < 0.05. Conclusions Levocarnitine supplementation is associated with repletion of plasma carnitine and improvement in myocardial strain and may benefit pediatric patients undergoing prolonged CKRT., Author(s): Kristen Sgambat [sup.1] , Sarah Clauss [sup.2] , Asha Moudgil [sup.1] Author Affiliations: (1) grid.239560.b, 0000 0004 0482 1586, Department of Nephrology, Children's National Hospital, , 111 Michigan Avenue [...]

Background Frailty is a condition of decreased physiologic reserve and increased vulnerability to stressors. Frailty in combination with inflammation has been associated with increased mortality risk in adults with advanced chronic kidney disease (CKD). This study aimed to investigate prevalence and outcomes associated with a frailty-inflammation phenotype, or 'fragility,' in children with CKD. Methods We analyzed 557 children (age 6-19 years, eGFR 30-90 ml/min/1.73 m.sup.2) from the Chronic Kidney Disease in Children (CKiD) study. Based on adult models, the CKiD fragility model included four indicators: (1) suboptimal growth/weight gain (BMI < 5th percentile-for-height-age, deceleration [greater than or equal to] 10 BMI-for-height-age percentiles/1 year, height-for-age percentile < 3rd or deceleration [greater than or equal to] 10 height percentiles/1 year); (2) low muscle mass (mid-upper-arm circumference 3 mg/l). Logistic regression was used to evaluate association of fragility indicators with three adverse outcomes: frequent infection (> 1 per year/3 years), hospitalization (any), and rapid CKD progression (decline in eGFR > 30% or initiation of renal replacement therapy within 3 years). Results Prevalence of fragility indicators 1 year after study entry were 39% (suboptimal growth/weight gain), 62% (low muscle mass), 29% (fatigue), and 18% (inflammation). Prevalence of adverse outcomes during the subsequent 3 years were 13% (frequent infection), 22% (hospitalization), and 17% (rapid CKD progression). Children with [greater than or equal to] 3 fragility indicators had 3.16-fold odds of frequent infection and 2.81-fold odds of hospitalization, but did not have rapid CKD progression. Conclusions A fragility phenotype, characterized by the presence of [greater than or equal to] 3 indicators, is associated with adverse outcomes, including infection and hospitalization in children with CKD., Author(s): Kristen Sgambat [sup.1] , Matthew B. Matheson [sup.2] , Stephen R. Hooper [sup.3] , Bradley Warady [sup.4] , Susan Furth [sup.5] , Asha Moudgil [sup.1] Author Affiliations: (Aff1) grid.239560.b, [...]

Background: There are scant data on the effect of rituximab on EBV DNA levels and prevention of post‐transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplant recipients with EBV DNAemia. Methods: Kidney transplant recipients with EBV DNAemia treated with rituximab to prevent PTLD between 7/1999 and 7/2019 at five pediatric centers were included. Those with confirmed PTLD at the onset of rituximab were excluded. Primary outcomes included percentage change in EBV DNAemia and occurrence of PTLD post rituximab. Results: Twenty‐six pediatric kidney transplant recipients were included. Median age at transplant was 4 years (IQR 2.1–10.3). EBV DNA load monitoring by qPCR was performed at 1–3 month intervals. EBV DNAemia onset occurred at a median of 73 days post‐transplant (IQR 52–307), followed by DNAemia peak at a median of 268 days (IQR 112–536). Rituximab was administered at a median of 9 days post peak (IQR 0–118). Rituximab regimens varied; median dose 375 mg/m2 (IQR 375–439) weekly for 1–4 doses per course. Following rituximab, EBV DNA load decreased to <10% of baseline at 120 days in 20/26 patients; however, only 30% achieved complete resolution at last follow‐up (median 2094 days post‐transplant [IQR 1538–3463]). Two (7%) developed PTLD at 915 and 1713 days post rituximab. All recipients had functioning grafts. One death occurred in a child with PTLD following remission due to unrelated reasons. Conclusions: In the largest pediatric kidney transplant recipient case series with EBV DNAemia given rituximab to prevent PTLD, rituximab achieved a short‐term reduction in DNA load; however, recurrent DNAemia is common. [ABSTRACT FROM AUTHOR]

Background: Mycophenolate Mofetil (MMF) is an effective immunosuppressant used in kidney transplant recipients to prevent acute rejection. Complications such as diarrhea, leukopenia, and infections may necessitate the reduction or discontinuation of MMF. The objective of the study was to investigate the prevalence, timing, and reasons for MMF discontinuation and its association with outcomes in pediatric kidney transplant recipients. Methods: Seven Pediatric Nephrology Research Consortium (PNRC) centers participated in a retrospective analysis of kidney transplant recipients <21 years of age. Characteristics and outcomes of patients in whom MMF was discontinued were compared to those who continued taking MMF throughout the first 2 years post‐transplant. Results: The study population included 288 participants (mean age 11.2 years) from 7 North American transplant centers. MMF was discontinued in 93/288 (32%) of participants. Common reasons for discontinuation included infections (35%), diarrhea (32%), leukopenia (15%), and others (18%). Increased cumulative alloimmunity (55% vs. 42%, p =.02), increased number of hospitalizations (82% vs. 67%, p =.01), and viral replications (79% vs. 47%, p <.0001) were observed in the MMF discontinuation group compared to the continuation group. Greater eGFR decline also occurred in the MMF discontinuation group over 2 years of follow‐up (−7 vs. −1 mL/min/1.73 m2, p =.05). Conclusions: Almost a third of pediatric kidney transplant recipients who begin MMF for maintenance immunosuppression have it discontinued within the first 2 years post‐transplant, and this subset of patients is more likely to experience adverse outcomes. New strategies are needed to manage MMF therapy and improve post‐transplant outcomes. [ABSTRACT FROM AUTHOR]

Background Cardiovascular (CV) risk is high in children with chronic kidney disease (CKD), and further compounded in those who are overweight. Children with CKD have a unique body habitus not accurately assessed by body mass index (BMI). Waist-to-height ratio (WHr), a better predictor of CV risk in populations with short stature, has not been investigated in children with CKD. Methods Analysis of 1723 visits of 593 participants enrolled in the Chronic Kidney Disease in Children (CKiD) study was conducted. CKiD participants had BMI and WHr measured and classified as follows: (1) lean (WHr [less than or equal to] 0.49, BMI 0.49, BMI < 85th percentile); (3) BMI-overweight (WHr [less than or equal to] 0.49, BMI [greater than or equal to] 85th percentile); or (4) overweight by both BMI and WHr. Left ventricular mass index (LVMI), fasting lipids, fibroblast growth factor 23 (FGF23), blood pressure, and glucose were measured as markers of CV risk. Linear mixed-effects regression was used to evaluate differences in CV markers between overweight and lean groups. Results Participants were 12.2 years old, 60% male, and 17% African-American. Approximately 15% were overweight by WHr but not by BMI. Overweight status by WHr-only or both WHr and BMI was associated with lower high-density lipoprotein (HDL) and higher LVMI, triglycerides, and non-HDL cholesterol compared to lean. CV markers of participants overweight by BMI-only were similar to those of lean children. Conclusions WHr-adiposity is associated with an adverse CV risk profile in children with CKD. A significant proportion of children with central adiposity are missed by BMI. WHr should be utilized as a screening tool for CV risk in this population., Author(s): Kristen Sgambat [sup.1] , Jennifer Roem [sup.2] , Mark Mitsnefes [sup.3] , Anthony A. Portale [sup.4] , Susan Furth [sup.5] , Bradley Warady [sup.6] , Asha Moudgil [sup.1] Author [...]

Background Obesity and metabolic syndrome (MS) are common after kidney transplantation, but their contribution to adverse cardiovascular (CV) outcomes in children are not well known. A prospective, controlled, longitudinal cohort study was conducted to investigate the effects of obesity and MS on left ventricular hypertrophy (LVH) and myocardial strain in pediatric kidney transplant recipients. Methods Transplant recipients (n = 42) had anthropometrics [body mass index (BMI), waist circumference, waist-to-height ratio], biochemical parameters (fasting glucose, lipid panel, HbA1c%), and echocardiogram with speckle tracking analysis for strain measured at 1, 18, and 30 months post-transplant. Additionally, 35 pre-transplant echocardiograms were analyzed retrospectively. Healthy children (n = 24) served as controls. Results Waist-to-height ratio detected abdominal obesity in 46% of transplant patients, whereas only 8.1% were identified as obese by waist circumference. Ejection fraction and fractional shortening of the transplant group were normal. Prevalence of LVH was 35.2%, 17.1%, and 35.5% at 1, 18, and 30 months respectively. The longitudinal strain of transplant group was worse than controls at all time points (p < 0.001). Hemodialysis was independently associated with 21% worse longitudinal strain during the pre-transplant period (p = 0.04). After transplantation, obesity, MS, and systolic hypertension predicted increased odds of LVH (p < 0.04). Worse longitudinal strain was independently associated with obesity, MS, hypertension, and the combination of MS with elevated low density lipoprotein (LDL) cholesterol (p < 0.04), whereas higher estimated glomerular filtration rate (eGFR) conferred a protective effect (p < 0.001). Conclusion Obesity and MS adversely affect CV outcomes after transplantation. Further studies are needed to investigate speckle tracking echocardiography as a tool for early detection of subclinical myocardial dysfunction in this population., Author(s): Kristen Sgambat [sup.1] , Sarah Clauss [sup.2] , K. Y. Lei [sup.3] , Jiuzhou Song [sup.4] , Shaik O. Rahaman [sup.3] , Margaret Lasota [sup.2] , Asha Moudgil [sup.1] [...]

Author(s): Rasheda Amin[sup.1] , Loai Eid[sup.2] , Vidar O. Edvardsson[sup.3] [sup.4] , Lynette Fairbanks[sup.5] , Asha Moudgil[sup.1] Author Affiliations: (1) Division of Pediatric Nephrology, Children's National Health System, 111 Michigan [...]

Children with multiple comorbidities, including neurodevelopmental delay, can develop end-stage kidney disease (ESKD). When and if these children should be eligible for kidney transplantation is an area of debate within the pediatric nephrology community and the public. Discussions focus on expected survival and quality of life posttransplant, as well as resource allocation decisions, as donor kidneys remain a limited resource. This paper focuses on the evidence available regarding outcomes in this population and the ethical issues that should be considered. The authors offer a framework for transplant teams evaluating children with comorbidities for kidney transplant, focusing on the benefits and burdens that transplantation can be expected to achieve., Author(s): Aviva M. Goldberg [sup.1] , Sandra Amaral [sup.2] , Asha Moudgil [sup.3] Author Affiliations: (1) grid.21613.37, 0000000419369609, Section of Nephrology, Department of Pediatrics and Child Health, Faculty of Medicine, [...]

Background Idiopathic steroid-resistant nephrotic syndrome (SRNS) has been associated with the presence of a circulating focal sclerosis permeability factor (FSPF) thought to damage the glomerular barrier and increase permeability to albumin. Galactose binds and inactivates FSPF in vitro, but its effect in vivo is uncertain. Methods A prospective clinical trial was conducted to investigate the effect of oral galactose on FSPF and proteinuria in children with SRNS. Seven pediatric subjects with idiopathic SRNS and positive FSPF activity (> 0.5) were treated with oral galactose (0.2 gm/kg/dose twice daily) for 16 weeks. Post-treatment FSPF and proteinuria were measured. Results Focal sclerosis permeability factor activity of the seven subjects decreased from 0.69 [+ or -] 0.11 to 0.35 [+ or -] 0.21 (p = 0.009) in response to galactose. The two subjects with post-transplant recurrence of focal segmental glomerulosclerosis (FSGS) demonstrated the most significant improvement in FSPF (p = 0.006). Despite this decrease in FSPF, the pre- and post-treatment urine protein: creatinine ratio remained unchanged and no subject achieved remission. Conclusions Galactose decreases FSPF in children with SRNS, with the most significant improvement in those with post-transplant FSGS recurrence, but it fails to improve proteinuria. At the present time there is no evidence to support the use of galactose in children with FSGS, either pre- or post-transplant. Future studies to investigate the role of galactose as preemptive therapy to decrease the risk of post-transplant FSGS recurrence may be useful. Keywords Focal segmental glomerulosclerosis * Pediatric * Kidney * Transplantation * Focal sclerosis permeability factor, Introduction Idiopathic steroid-resistant nephrotic syndrome (SRNS) in children is characterized by a high risk of progression to end-stage renal disease, post-transplant disease recurrence [1] and an overall increased risk of [...]