Developing a Research Mentorship Program: The American Society of Pediatric Nephrology's Experience

Background: Most pediatric nephrologists work in academia. Mentor-mentee relationships provide support and guidance for successful research career. Mentorship program implementation is valuable in medical fields for providing research opportunities to young faculty. Methods: The American Society of Pediatric Nephrology (ASPN) established a research mentorship program to (a) assist with matching of appropriate mentor-mentee dyads and (b) establish metrics for desirable mentor-mentee outcomes with two independent components: (1) the grants review workshop, a short-term program providing mentor feedback on grant proposals, and (2) the longitudinal program, establishing long-term mentor-mentee relationships. Regular surveys of both mentors and mentees were reviewed to evaluate and refine the program. Results: Twelve mentees and 17 mentors participated in the grant review workshop and 19 mentees were matched to mentors in the longitudinal program. A review of NIH RePORTER data indicated that since 2014, 13 NIH grants have been awarded. Mentees in the longitudinal program reported that the program helped most with identifying an outside mentor, improving grant research content, and with general career development. Mentors perceived themselves to be most helpful in assisting with overall career plans. Email communications were preferred over phone or face-to-face communications. Mentees endorsed strong interest in staying in touch with their mentors and 100% of mentors expressed their willingness to serve in the future. Conclusion: This mentorship program was initiated and supported by a relatively small medical society and has shown early success in cultivating mentoring relationships for a future generation of clinician-scientists

Age-related differences in adaptive decision making: Sensitivity to expected value in risky choice

While previous research has found that children make more risky decisions than their parents, little is known about the developmental trajectory for the ability to make advantageous decisions. In a sample of children, 5--11 years old, we administered a new risky decision making task in which the relative expected value (EV) of the risky and riskless choice options was varied over trials. Younger children (age 5--7) showed significantly less responsiveness to EV differences than their parents on both trials involving risky gains and trials involving risky losses. For older children (age 8--11) this deficit was smaller overall but was greater on loss trials than on gain trials. Children of both ages made more risky choices than adults when risky choices were disadvantageous. We further analyzed these results in terms of children's ability to utilize probability and outcome information, and discussed them in terms of developing brain structures vital for decision making under uncertainty.risky decision making, child-adult differences, reward sensitivity

An Improved Postprocessing Method to Mitigate the Macroscopic Cross-Slice <i>B</i>₀ Field Effect on <inline-formula><math display="inline"><semantics><mrow><msubsup><mrow><mi>R</mi></mrow><mrow><mn>2</mn></mrow><mrow><mi>*</mi></mrow></msubsup></mrow></semantics></math></inline-formula> Measurements in the Mouse Brain at 7T

The MR transverse relaxation rate, R2*, has been widely used to detect iron and myelin content in tissue. However, it is also sensitive to macroscopic B0 inhomogeneities. One approach to correct for the B0 effect is to fit gradient-echo signals with the three-parameter model, a sinc function-weighted monoexponential decay. However, such three-parameter models are subject to increased noise sensitivity. To address this issue, this study presents a two-stage fitting procedure based on the three-parameter model to mitigate the B0 effect and reduce the noise sensitivity of R2* measurement in the mouse brain at 7T. MRI scans were performed on eight healthy mice. The gradient-echo signals were fitted with the two-stage fitting procedure to generate R2corr_t*. The signals were also fitted with the monoexponential and three-parameter models to generate R2nocorr* and R2corr*, respectively. Regions of interest (ROIs), including the corpus callosum, internal capsule, somatosensory cortex, caudo-putamen, thalamus, and lateral ventricle, were selected to evaluate the within-ROI mean and standard deviation (SD) of the R2* measurements. The results showed that the Akaike information criterion of the monoexponential model was significantly reduced by using the three-parameter model in the selected ROIs (p = 0.0039–0.0078). However, the within-ROI SD of R2corr* using the three-parameter model was significantly higher than that of the R2nocorr* in the internal capsule, caudo-putamen, and thalamus regions (p = 0.0039), a consequence partially due to the increased noise sensitivity of the three-parameter model. With the two-stage fitting procedure, the within-ROI SD of R2corr* was significantly reduced by 7.7–30.2% in all ROIs, except for the somatosensory cortex region with a fast in-plane variation of the B0 gradient field (p = 0.0039–0.0078). These results support the utilization of the two-stage fitting procedure to mitigate the B0 effect and reduce noise sensitivity for R2* measurement in the mouse brain

Nutritional management of the child with chronic kidney disease and on dialysis

While it is widely accepted that the nutritional management of the infant with chronic kidney disease (CKD) is paramount to achieve normal growth and development, nutritional management is also of importance beyond 1 year of age, particularly in toddlers, to support the delayed infantile stage of growth that may extend to 2-3 years of age. Puberty is also a vulnerable period when nutritional needs are higher to support the expected growth spurt. Inadequate nutritional intake throughout childhood can result in failure to achieve full adult height potential, and there is an increased risk for abnormal neurodevelopment. Conversely, the rising prevalence of overweight and obesity among children with CKD underscores the necessity for effective nutritional strategies to mitigate the risk of metabolic syndrome that is not confined to the post-transplant population. Nutritional management is of primary importance in improving metabolic equilibrium and reducing CKD-related imbalances, particularly as the range of foods eaten by the child widens as they get older (including increased consumption of processed foods), and as CKD progresses. The aim of this review is to integrate the Pediatric Renal Nutrition Taskforce (PRNT) clinical practice recommendations (CPRs) for children (1-18 years) with CKD stages 2-5 and on dialysis (CKD2-5D). We provide a holistic approach to the overall nutritional management of the toddler, child, and young person. Collaboration between physicians and pediatric kidney dietitians is strongly advised to ensure comprehensive and tailored nutritional care for children with CKD, ultimately optimizing their growth and development

Antibody-Mediated Rejection in Pediatric Kidney Transplant Recipients: A Report From the Pediatric Nephrology Research Consortium

BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. There is a paucity of large-scale pediatric-specific data regarding AMR treatment outcomes. METHODS: Data were obtained from 14 centers within the Pediatric Nephrology Research Consortium. Kidney transplant recipients aged 1-18 years at transplant with biopsy-proven AMR between 2009 and 2019 and at least 12 months of follow-up were included. The primary outcome was graft failure or an eGFR \u3c20 mL/min/1.73 m at 12 months following AMR treatment. AMR treatment choice, histopathology, and DSA class were also examined. RESULTS: We reviewed 123 AMR episodes. Median age at diagnosis was 15 years at a median 22 months post-transplant. The primary outcome developed in 27.6%. eGFR \u3c30 m/min/1.73 m at AMR diagnosis was associated with a 5.6-fold higher risk of reaching the composite outcome. There were no significant differences in outcome by treatment modality. Histopathology scores and DSA class at time of AMR diagnosis were not significantly associated with the primary outcome. CONCLUSIONS: In this large cohort of pediatric kidney transplant recipients with AMR, nearly one-third of patients experienced graft failure or significant graft dysfunction within 12 months of diagnosis. Poor graft function at time of diagnosis was associated with higher odds of graft failure

COVID-19 in pediatric kidney transplantation: a follow-up report of the Improving Renal Outcomes Collaborative

BackgroundWe report follow-up data from an ongoing prospective cohort study of COVID-19 in pediatric kidney transplantation through the Improving Renal Outcomes Collaborative (IROC).MethodsPatient-level data from the IROC registry were combined with testing, indication, and outcomes data collected to describe the epidemiology of COVID testing, treatment, and clinical outcomes; determine the incidence of a positive COVID-19 test; describe rates of COVID-19 testing; and assess for clinical predictors of a positive COVID-19 test.ResultsFrom September 2020 to February 2021, 21 centers that care for 2690 patients submitted data from 648 COVID-19 tests on 465 patients. Most patients required supportive care only and were treated as outpatients, 16% experienced inpatient care, and 5% experienced intensive care. Allograft complications were rare, with acute kidney injury most common (7%). There was 1 case of respiratory failure and 1 death attributed to COVID-19. Twelve centers that care for 1730 patients submitted complete testing data on 351 patients. The incidence of COVID-19 among patients at these centers was 4%, whereas the incidence among tested patients was 19%. Risk factors to predict a positive COVID-19 test included age &gt; 12&nbsp;years, symptoms consistent with COVID-19, and close contact with a confirmed case of COVID-19.ConclusionsDespite the increase in testing and positive tests over this study period, the incidence of allograft loss or death related to COVID-19 remained extremely low, with allograft loss or death each occurring in &lt; 1% of COVID-19-positive patients and in less than &lt; 0.1% of all transplant patients within the IROC cohort. A higher resolution version of the Graphical abstract is available as Supplementary information

The Preserving Kidney Function in Children With CKD (PRESERVE) Study: Rationale, Design, and Methods

PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management. Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]). PRESERVE will include approximately 20,000 children between January 2009-December 2022 with mild-moderate CKD from 15 health care institutions that participate in 6 PCORnet Clinical Research Networks (PEDSnet, STAR, GPC, PaTH, CAPRiCORN, and OneFlorida+). The inclusion criteria were≥1 nephrologist visit and≥2 estimated glomerular filtration rate (eGFR) values in the range of 30 to<90mL/min/1.73m2 separated by≥90 days without an intervening value≥90mL/min/1.73m2 and no prior dialysis or kidney transplant. BP measurements (clinic-based and 24-hour ambulatory BP); urine protein; and antihypertensive treatment by therapeutic class. The primary outcome is a composite event of a 50% reduction in eGFR, eGFR of<15mL/min/1.73m2, long-term dialysis or kidney transplant. Secondary outcomes include change in eGFR, adverse events, and PROs. Longitudinal models for dichotomous (proportional hazards or accelerated failure time) and continuous (generalized linear mixed models) clinical outcomes; multivariable linear regression for PROs. We will evaluate heterogeneity of treatment effect by CKD etiology and degree of proteinuria and will examine variation in hypertension management and outcomes based on socio-demographics. Causal inference limited by observational analyses. PRESERVE will leverage the PCORnet infrastructure to conduct large-scale observational studies that address BP management knowledge gaps for pediatric CKD, focusing on outcomes that are meaningful to patients. Hypertension is a major modifiable contributor to loss of kidney function in chronic kidney disease (CKD). The purpose of PRESERVE is to provide evidence to inform shared decision-making regarding blood pressure management for children with CKD. PRESERVE is a consortium of 16 health care institutions in Patient-Centered Clinical Research Network (PCORnet), the National Patient-Centered Clinical Research Network, and includes electronic health record data for>19,000 children with CKD. PRESERVE will (1) expand the PCORnet infrastructure for research in pediatric CKD by adding kidney-specific variables and linking electronic health record data to other kidney disease databases; (2) compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; and (3) assess the lived experiences of patients and caregivers related to blood pressure management

Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter analysis

Methylmalonic acidemia (MMAemia) is characterized by accumulation of methylmalonic acid (MMA) in all body tissues. To minimize disease-related complications, isolated kidney (KTx), liver (LTx) or com- bined liver-kidney transplantation (LKTx) have been suggested. However, the impact of these different trans- plant strategies on outcome are unclear. Methods: In this multicenter retrospective observational study, we compared plasma MMA levels and estimated glomerular filtration rate (eGFR) data of 83 patients. Sixty-eight patients (82%) had a mut0 -type MMAemia, one patient had a mut−-type MMAemia, and seven (7.3%) had an inherited defect in cobalamin metabolism (cblA- or cblB-type MMAemia). Median observation period was 3.7 years (0–15.1 years). Results: Twenty-six (31%) patients underwent KTx, 24 (29%) LTx and 33 (40%) LKTx. Posttransplant, mean plasma MMA concentration significantly decreased in all three cohorts; but at month 12, plasma MMA in KTx (1372 ± 1101 μmol/L) was 7.8-fold higher than in LTx (176 ± 103 μmol/L; P &lt; 0.001) and 6.4-fold higher than in LKTx (215 ± 110 μmol/L; P &lt; 0.001). Comparable data were observed at month 24. At time of transplan- tation, mean eGFR in KTx was 18.1 ± 24.3 mL/min/1.73 m2 , in LTx 99.8 ± 29.9 mL/min/1.73 m2 , and in LKTx 31.5</p

ALG1-CDG: Clinical and Molecular Characterization of 39 Unreported Patients

Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over 100 genes leading to impaired protein or lipid glycosylation. ALG1 encodes a beta 1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date 13 mutations in 18 patients from 14 families have been described with varying degrees of clinical severity. We identified and characterized 39 previously unreported cases of ALG1-CDG from 32 families and add 26 new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2, was seen in all 27 patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder. (C) 2016 Wiley Periodicals, Inc