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The revised 2018 ISN/RPS Classification System for lupus nephritis (LN) includes calculations for both activity index (A.I.) and chronicity index (C.I.). Unchanged were the thresholds of 25%, 25-50%, and 50% crescents to distinguish between mild, moderate, and severe activity/chronicity. We aimed to evaluate these thresholds for percent crescents in childhood-onset LN.Eighty-six subjects 21 years of age were enrolled from the Pediatric Glomerulonephritis with Crescents Registry, a retrospective multi-center cohort sponsored by the Pediatric Nephrology Research Consortium. Thresholds of 10%, 25%, and 50% for both cellular/fibrocellular and fibrous crescents were interrogated for primary outcomes of kidney failure, eGFR, and eGFR slope.Median age at time of initial biopsy was 14 years (range 1-21). Median follow-up time was 3 years (range 1-11). Cumulative incidence of kidney failure was 6% at 1 year and 10% at latest follow-up. Median eGFR slope was - 18 mL/1.73 mIn children with crescentic LN, use of 10% and 25% thresholds for cellular crescents better reflects disease activity, while these thresholds for fibrous crescents better discriminates kidney disease outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

OBJECTIVE To describe three different standardized approaches to improving neonatal acute kidney injury (AKI) identification and the impact on AKI identification, incidence, and nephrology consultation and referral. STUDY DESIGN A retrospective cohort study in three academic NICUs. We compared AKI identification, AKI incidence, nephrology consultation, and nephrology follow-up before and after implantation of local protocols to standardize neonatal AKI identification. RESULT Neonatal AKI identification improved in all three NICUs following protocol implementation (26-85%, P

Introduction: Disparities in health-related quality of life (HRQOL) have been inadequately studied in patients with glomerular disease. The aim of this study was to identify relationships among race/ethnicity, socioeconomic status, disease severity, and HRQOL in an ethnically and racially diverse cohort of patients with glomerular disease. Methods: Cure Glomerulonephropathy (CureGN) is a multinational cohort study of patients with biopsy-proven glomerular disease. Associations between race/ethnicity and HRQOL were determined by the following: (1) missed school or work due to kidney disease and (2) responses to Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires. We adjusted for demographics, socioeconomic status, and disease characteristics using multivariable logistic and linear regression. Results: Black and Hispanic participants had worse socioeconomic status and more severe glomerular disease than white or Asian participants. Black adults missed work or school most frequently due to kidney disease (30 vs. 16–23% in the other 3 groups, p = 0.04), and had the worst self-reported global physical health (median score 44.1 vs. 48.0–48.2, p < 0.001) and fatigue (53.8 vs. 48.5–51.1, p = 0.002), compared to other racial/ethnic groups. However, these findings were not statistically significant with adjustment for socioeconomic status and disease severity, both of which were strongly associated with HRQOL in adults. Among children, disease severity but not race/ethnicity or socioeconomic status was associated with HRQOL. Conclusions: Among patients with glomerular disease enrolled in CureGN, the worse HRQOL reported by black adults was attributable to lower socioeconomic status and more severe glomerular disease. No racial/ethnic differences in HRQOL were observed in children.

BACKGROUND AND AIMS Kidney allograft loss is a common cause of end-stage renal disease but accurate prediction models of kidney allograft loss are lacking in children. The iBOX system has been broadly validated among adults. We aimed to validate the iBOX system in a large international cohort of pediatric kTx recipients. METHOD In this observational study, we used data from pediatric ( RESULTS A total of 573 kTx recipients were included. Median time from transplantation to evaluation was 1.0 (0.5–2.0) year with a mean age at evaluation at 12.1 (5.5) years and mean follow-up after transplantation 5.1 (2.8) years. Five-year death-censored graft survival from evaluation was 95%. At the time of evaluation, mean eGFR and uPCR were 65.5 (29.6) mL/min/1.73 m2 and 0.25 (1.2) g/g, respectively. A total of 118 (20.6%) of the patients had DSA. The iBOX system showed good discrimination with a c-statistic of 0.81 and good calibration (Figure 1). CONCLUSION The iBOX system demonstrated high accuracy in predicting kidney allograft loss in children with performances similar to those reported in adults.

Pseudohypoaldosteronism type I is caused by a peripheral resistance to aldosterone and can present with electrolyte abnormalities, poor growth, or dehydration. Although a rare disease, several case reports have been published regarding Pseudohypoaldosteronism type I in neonates and infants. We report a case of failure to thrive and hyponatremia in an infant with hypoplastic left heart syndrome who was subsequently found to have Pseudohypoaldosteronism type I.

Introduction Glomerular diseases are characterized by variable disease activity over many years. We aimed to analyze the relationship between clinical disease activity and duration of glomerular disease. Methods Disease activity in adults with chronic minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy (IgAN; first diagnostic biopsy >5 years before enrollment; Of Longstanding Disease [OLD] cohort, n = 256) followed at Columbia University Medical Center (CUMC), was compared with disease activity of an internal and external cohort of patients with first diagnostic biopsy, Graphical abstract

The effects of race, ethnicity, socioeconomic status (SES), and disease severity on acute care utilization in patients with glomerular disease are unknown.Prospective cohort study.1,456 adults and 768 children with biopsy-proven glomerular disease enrolled in the Cure Glomerulonephropathy (CureGN) cohort.Race and ethnicity as a participant-reported social factor.Acute care utilization defined as hospitalizations or emergency department visits.Multivariable recurrent event proportional rate models were used to estimate associations between race and ethnicity and acute care utilization.Black or Hispanic participants had lower SES and more severe glomerular disease than White or Asian participants. Acute care utilization rates were 45.6, 29.5, 25.8, and 19.2 per 100 person-years in Black, Hispanic, White, and Asian adults, respectively, and 55.8, 42.5, 40.8, and 13.0, respectively, for children. Compared with the White race (reference group), Black race was significantly associated with acute care utilization in adults (rate ratio [RR], 1.76 [95% CI, 1.37-2.27]), although this finding was attenuated after multivariable adjustment (RR, 1.31 [95% CI, 1.03-1.68]). Black race was not significantly associated with acute care utilization in children; Asian race was significantly associated with lower acute care utilization in children (RR, 0.32 [95% CI 0.14-0.70]); no significant associations between Hispanic ethnicity and acute care utilization were identified.We used proxies for SES and lacked direct information on income, household unemployment, or disability.Significant differences in acute care utilization rates were observed across racial and ethnic groups in persons with prevalent glomerular disease, although many of these difference were explained by differences in SES and disease severity. Measures to combat socioeconomic disadvantage in Black patients and to more effectively prevent and treat glomerular disease are needed to reduce disparities in acute care utilization, improve patient wellbeing, and reduce health care costs.

Introduction The slow increase in use of telemedicine began to expand rapidly, along with reimbursement changes, during the coronavirus disease-2019 (COVID-19) pandemic. Standardized protocols for these services are lacking but are needed for effective and equitable health care. In this study, we queried pediatric nephrologists and their patients about their telemedicine experiences during the pandemic. Methods Surveys that were in compliance with the Health Insurance Portability and Accountability Act were deployed online to patients and physicians. Results We collected survey responses from 400 patients and 197 pediatric nephrologists. Patients reported positive experiences with telemedicine visits as it was logistically easier than in-person visits. Patients also felt that the quality of their visits were equivalent to what they would receive in person. Physicians used a wide variety of online systems to conduct synchronous telemedicine with Zoom (23%), EPIC (9%), Doxy.me (7%), services not specified (37%), or a mix of local or smaller services (24%). Most physicians' concerns were related to technological issues and the ability to procure physical exams and/or laboratory results. Conclusions There is a paucity of published trials on telemedicine services in pediatric nephrology. Virtual care was feasible and acceptable for patients, caregivers, and providers during the COVID-19 pandemic., Graphical abstract

Lung opacification on chest radiography (CXR) is common during extracorporeal life support (ECLS), often resulting from pulmonary edema or inflammation. Concurrent use of continuous renal replacement therapy (CRRT) during ECLS is associated with improved fluid balance and cytokine filtration; through modification of these pathologic states, CRRT may modulate lung opacification observed on CXRs. We hypothesize that early CRRT use during infant ECLS decreases lung opacification on CXR. We conducted a retrospective cohort study comparing CXRs from infants receiving ECLS and early CRRT (n = 7) to matched infants who received ECLS alone (n = 7). The CXR obtained prior to ECLS, all CXRs obtained within the first 72 h of ECLS, and daily CXRs for the remainder of the ECLS course were analyzed. The outcome measure was the degree of opacification, determined by independent assessment of two, blinded pediatric radiologists using a modified Edwards et al.’s lung opacification scoring system (from Score 0: no opacification to Score 5: complete opacification). 220 CXRs were assessed (cases: 93, controls: 127). Inter-rater reliability was established (Cohen’s weighted к = 0.74; p

Renal damage is a progressive complication of sickle cell disease (SCD). Microalbuminuria is common in children with SCD, while a smaller number of children have more severe renal manifestations necessitating kidney biopsy. There is limited information on renal biopsy findings in children with SCD and subsequent management and outcome. This is a multicenter retrospective analysis of renal biopsy findings and clinical outcomes in children and adolescents with SCD. We included children and adolescents (age ≤ 20 years) with SCD who had a kidney biopsy performed at a pediatric nephrology unit. The clinical indication for biopsy, biopsy findings, subsequent treatments, and outcomes were analyzed. Thirty-six SCD patients (ages 4–19 years) were identified from 14 centers with a median follow-up of 2.6 years (0.4–10.4 years). The indications for biopsy were proteinuria (92%) and elevated creatinine (30%). All biopsies had abnormal findings, including mesangial hypercellularity (75%), focal segmental glomerulosclerosis (30%), membranoproliferative glomerulonephritis (16%), and thrombotic microangiopathy (2%). There was increased use of hydroxyurea, angiotensin-converting-enzyme inhibitors, and angiotensin receptor blockers following renal biopsy. At last follow-up, 3 patients were deceased, 2 developed insulin-dependent diabetes mellitus, 6 initiated chronic hemodialysis, 1 received a bone marrow transplant, and 1 received a kidney transplant. Renal biopsies, while not commonly performed in children with SCD, were universally abnormal. Outcomes were poor in this cohort of patients despite a variety of post-biopsy interventions. Effective early intervention to prevent chronic kidney disease (CKD) is needed to reduce morbidity and mortality in children with SCD.

Henoch-Schönlein purpura nephritis and immunoglobulin A nephropathy are common glomerulopathies in the pediatric population that deserve special attention. In some cases the primary care provider can follow the patient but others need more intensive management. Delaying this treatment can lead to worse morbidity. This article provides information on the pathogenesis, outcomes, and follow-up strategies that will aid in the diagnosis and referral of patients at risk for kidney disease.

To describe three different standardized approaches to improving neonatal acute kidney injury (AKI) identification and the impact on AKI identification, incidence, and nephrology consultation and referral.A retrospective cohort study in three academic NICUs. We compared AKI identification, AKI incidence, nephrology consultation, and nephrology follow-up before and after implantation of local protocols to standardize neonatal AKI identification.Neonatal AKI identification improved in all three NICUs following protocol implementation (26-85%, P 0.0001). Each center also saw increases in nephrology consultation (15-83%, P 0.0001) and nephrology follow-up (7-73%, P 0.0001). AKI incidence decreased significantly (21-12%, P 0.0001).Multiple strategies can be successfully operationalized to improve neonatal AKI identification. While different in approach, each strategy resulted in increased AKI identification and nephrology involvement. This study emphasizes the importance of local standardized approaches to AKI to improve AKI identification and nephrology involvement in the NICU.

INTRODUCTION There are no guidelines regarding management of failed pediatric renal transplants. MATERIALS & METHODS We performed a first of its kind multicenter study assessing prevalence of transplant nephrectomy, patient characteristics, and outcomes in pediatric renal transplant recipients with graft failure from January 1, 2006, to December 31, 2016. RESULTS Fourteen centers contributed data on 186 pediatric recipients with failed transplants. The 76 recipients that underwent transplant nephrectomy were not significantly different from the 110 without nephrectomy in donor or recipient demographics. Fifty-three percent of graft nephrectomies were within a year of transplant. Graft tenderness prompted transplant nephrectomy in 91% (P

BackgroundChildren are recognised as at lower risk of severe COVID-19 compared with adults, but the impact of immunosuppression is yet to be determined. This study aims to describe the clinical course of COVID-19 in children with kidney disease taking immunosuppressive medication and to assess disease severity.MethodsCross-sectional study hosted by the European Rare Kidney Disease Reference Network and supported by the European, Asian and International paediatric nephrology societies. Anonymised data were submitted online for any child (age Results113 children were reported in this study from 30 different countries. Median age: 13 years (49% male). Main underlying reasons for immunosuppressive therapy: kidney transplant (47%), nephrotic syndrome (27%), systemic lupus erythematosus (10%). Immunosuppressive medications used include: glucocorticoids (76%), mycophenolate mofetil (MMF) (54%), tacrolimus/ciclosporine A (58%), rituximab/ofatumumab (11%). 78% required no respiratory support during COVID-19 illness, 5% required bi-level positive airway pressure or ventilation. Four children died; all deaths reported were from low-income countries with associated comorbidities. There was no significant difference in severity of COVID-19 based on gender, dialysis status, underlying kidney condition, and type or number of immunosuppressive medications.ConclusionsThis global study shows most children with a kidney disease taking immunosuppressive medication have mild disease with SARS-CoV-2 infection. We therefore suggest that children on immunosuppressive therapy should not be more strictly isolated than children who are not on immunosuppressive therapy.

Steroid-resistant nephrotic syndrome (SRNS) is a major cause of stage 5 chronic kidney disease (CKD 5) in children. LDL apheresis (LDL-A) is now FDA approved for the treatment of pediatric focal segmental glomerulosclerosis (FSGS). Effective management of hyperlipidemia with LDL-A in SRNS patients may prevent progression of kidney disease and lead to remission. We report a case series of patients who received LDL-A for treatment of SRNS METHODS: We describe five children with SRNS who were treated with 12 sessions of LDL-A. Partial remission (PR) is defined as urine protein to creatinine ratio (UPC) of 0.2-2 (g/g) or decrease in UPC ≥ 50%, and complete remission (CR) is defined as UPC 0.2 (g/g).One patient achieved CR and three achieved PR. One patient did not respond to therapy. The earliest that a patient achieved PR was at treatment #10 and some did not respond until after LDL-A was completed. Those who responded stayed in either CR or PR for extended periods of time. LDL-A was successful at significantly reducing LDL (p 0.001), total cholesterol (p 0.001), and triglyceride (p 0.001).LDL-A was able to significantly decrease the lipid levels in these patients and induce CR and PR in the majority. The current study confirms previous studies showing those with a higher glomerular sclerosis burden were less likely to respond. LDL-A should be considered in patients with treatment-resistant SRNS and should be considered before there is a high burden of glomerular sclerosis to provide the best chance of success.

BACKGROUND: Diarrhea is a common problem in the pediatric post-solid organ transplant and post-hematopoietic stem cell transplant populations. Infectious etiology incidences are poorly defined, and the possibility of multi-organism positivity is often uninvestigated. The aim of this study is to utilize stool multiplex GIP assays to compare the PTP and NTP regarding the incidence and profiles of single-organism and multi-organism infectious diarrhea. METHODS: A single-center retrospective review was conducted, investigating stool multiplex GIP panel results over a more than 3-year period, for pediatric patients. Assays test for 23 viral, bacterial, and protozoal organisms. RESULTS: Positive assays in the PTP and NTP were 70/101 (69.3%) and 962/1716 (56.1%), respectively (P = .009). Thirty-two percent (32/101) of assays within the PTP were multi-organism positive, significantly more than 14.8% (254/1716) in the NTP (P < .00001). There was no significant difference in the incidence of single-organism positives, 37.6% (38/101) in PTP and 41.3% (708/1716) in the NTP. The PTP demonstrated a statistically significantly higher incidence of the following organisms within multi-agent positive GIPs (P < .05 for each): Clostridioides difficile, Cryptosporidium, EPEC, norovirus, and sapovirus. CONCLUSIONS: The pediatric PTP demonstrates higher incidence of positive GIPs, higher rate of multi-organism positivity, and unique infectious organism incidence profiles. These data can provide a framework for understanding organism-specific pathogenicity factors, assessing the clinical impact of enteric co-infection, and understanding the utility of this testing modality in this unique population.

To assess pediatrician adherence to the 2017 American Academy of Pediatrics' clinical practice guideline for high blood pressure (BP).Pediatric primary care practices (n = 59) participating in a quality improvement collaborative submitted data for patients with high BP measured between November 2018 and January 2019. Baseline data included patient demographics, BP, body mass index (BMI), and actions taken. Logistic regression was used to test associations between patient BP level and BMI with provider adherence to guidelines (BP measurement, counseling, follow-up, evaluation).A total of 2677 patient charts were entered for analysis. Only 2% of patients had all BP measurement steps completed correctly, with fewer undergoing 3-limb and ambulatory BP measurement. Overall, 46% of patients received appropriate weight, nutrition, and lifestyle counseling. Follow-up for high BP was recommended or scheduled in 10% of encounters, and scheduled at the appropriate interval in 5%. For patients presenting with their third high BP measurement, 10% had an appropriate diagnosis documented, 2% had appropriate screening laboratory tests conducted, and none had a renal ultrasound performed. BMI was independently associated with increased odds of counseling, but higher BP was associated with lower odds of counseling. Higher BP was independently associated with an increased likelihood of documentation of hypertension.In this multisite study, adherence to the 2017 American Academy of Pediatrics' guideline for high BP was low. Given the long-term health implications of high BP in childhood, it is important to improve primary care provider recognition and management.ClinicalTrials.gov: NCT03783650.

Optimizing nutrition in neonatal patients as soon as possible after extracorporeal life support (ECLS) initiation is imperative as malnutrition can worsen both short- and long-term outcomes. Fluid restriction, used to manage the fluid overload that commonly complicates neonatal ECLS, severely impairs nutrition delivery. Continuous renal replacement therapy (CRRT) can be used to help manage fluid overload. We hypothesize that early CRRT utilization ameliorates the need for fluid restriction and allows providers to prescribe higher parenteral nutrition (PN) volumes leading to better nutrition delivery.The design of the study was a retrospective chart review, and the setting was a single, level III neonatal intensive care unit.Neonatal patients (n = 42) treated with ECLS between January 1, 2008, and December 31, 2013.Comparisons were made between 2 groups: neonates who received ECLS without early CRRT initiation (group 1; n = 23) and with early CRRT initiation (group 2; n = 19).The main outcome measures were goal total fluid intake, prescribed PN volume, protein, glucose infusion rate, intralipid, and kilocalories.Infants who received early CRRT were prescribed higher mean total fluid intake goals (group 1: 99 mL/kg/day vs. group 2: 119 mL/kg/day, P .001) and higher mean volumes of PN (group 1: 61 mL/kg/day vs. group 2: 81 mL/kg/day, P .001) over the first 72 hours of ECLS compared with infants who did not receive early CRRT. Early CRRT receivers also were prescribed greater mean amounts of protein during the first 72 hours of ECLS (group 1: 2.7 g/kg/day vs. group 2: 3 g/kg/day, P = 0.03). There were no significant changes noted in prescribed glucose infusion rates, intralipid, or total kilocalories.Institution of early CRRT in neonates on ECLS allows for administration of greater volumes of PN with improved protein delivery. This study characterizes one benefit of early CRRT initiation in neonates on ECLS and suggests these patients could experience improved nutritional outcomes.

Background: Kidney transplant (KT) recipients have higher incidence of malignancies, including Human Papillomavirus (HPV)-associated cancers. Thus, HPV vaccines may have an important role in preventing HPV-related disease in this population; however, immunogenicity and safety data are lacking. Objective: To examine the immunological response and tolerability to HPV vaccination in pediatric KT recipients compared to future KT candidates. Methods: The quadrivalent HPV vaccine was administered to girls and boys age 9-18 recruited from seven centers part of the Pediatric Nephrology Research Consortium. Subjects were recruited for three groups: (1) CKD: chronic kidney disease stages 3, 4, and 5 not on dialysis; (2) Dialysis; (3) KT recipients. The outcome consisted of antibody concentrations against HPV 6, 11, 16, and 18. Geometric mean titers (GMTs) and seroconversion rates were compared. Vaccine tolerability was assessed. Results: Sixty-five participants were recruited: 18 in the CKD, 18 in the dialysis, and 29 into the KT groups. KT patients had significantly lower GMTs after vaccination for all serotypes. The percentages of subjects who reached seroconversion were overall lower for the KT group, reaching statistical significance for HPV 6, 11, and 18. Comparing immunosuppressed subjects (anyone taking immunosuppression medications, whether KT recipient or not) with the non-immunosuppressed participants, the former had significantly lower GMTs for all the HPV serotypes and lower seroconversion rates for HPV 6, 11, and 18. KT females had higher GMTs and seroconversion rates for certain serotypes. There were no adverse events in either group. Conclusions: HPV vaccine was well-tolerated in this population. Pediatric KT recipients had in general lower GMTs and seroconversion rates compared to their peers with CKD or on dialysis. Immunosuppression played a role in the lack of seroconversion. Our results emphasize the importance of advocating for HPV vaccination prior to KT and acknowledge its safety post transplantation. Future studies are needed to investigate the effect of a supplemental dose of HPV vaccine in KT recipients who do not seroconvert and to evaluate the long-term persistence of antibodies post-KT.

Background: Focal segmental glomerulosclerosis (FSGS) causes end stage renal disease (ESRD) in significant proportion of patients worldwide. Primary FSGS carries poor prognosis and management of FSGS patients, refractory to standard treatments or resistant to steroids, remains a major challenge. Lipoprotein apheresis is a therapeutic approach for drug resistant primary FSGS and post-renal transplant primary FSGS recurrence. Objectives: To examine the safety and probable benefit at 1, 3, 6, 12, and 24-months following completion of apheresis treatment using Liposorber® LA-15 system in patients with nephrotic syndrome (NS), due to refractory primary FSGS or primary FSGS associated NS, in post renal transplant children. Material and Methods: Prospective, multicenter, single-arm intervention study using Liposorber® LA-15 system. Patients ≤21 years old with drug resistant or drug intolerant NS secondary to primary FSGS with glomerular filtration rate (GFR) ≥60 ml/min/1.73 m2 or post renal transplant patients ≤21 years old with primary FSGS associated NS were included in the study. Each patient had 12 dextran-sulfate plasma adsorption lipoprotein apheresis sessions over a period of 9 weeks. All patients were followed up at 1, 3, 6, 12, and 24-months following completion of treatment. Results: Of 17 patients enrolled, six were excluded from the outcome analysis (protocol deviations). Of the remaining 11 patients, all but one have completed apheresis treatments. Three patients were lost to follow-up immediately after completion of apheresis and excluded from outcome analysis. At one-month follow-up, 1 of 7 patients (14.3%) attained partial remission of NS while 2 of 4 subjects (50%) and 2 of 3 subjects (66.7%) had partial/complete remission at 3- and 6-months follow-up, respectively. One of two patients followed up for 12 months had complete remission and one patient had partial remission of NS after 24 months. Improved or stable eGFR was noted in all patients over the follow-up period. Conclusion: The results of our multicenter study showed improvement in the response rates to steroid or immunosuppressive therapy and induced complete or partial remission of proteinuria in some of the patients with drug resistant primary FSGS. The main limitation of our study is the small number of subjects and high dropout rate.

BACKGROUND Studies demonstrate that neonatal acute kidney injury (AKI) is associated with increased morbidity and mortality. Acute kidney injury survivors are at risk for renal dysfunction and chronic kidney disease and require long-term follow-up. PURPOSE To maximize identification of AKI and ensure referral, we created guidelines for diagnosis, evaluation, and management of AKI. METHODS/SEARCH STRATEGY Retrospective cohort study of neonatal intensive care unit patients treated before guideline implementation (cohort 1; n = 175) and after (cohort 2; n = 52). Outcome measures included AKI incidence, documented diagnosis, and pediatric nephrology consultation. Statistical methods included t tests, Fisher exact tests, and Wilcoxon rank sum tests. FINDINGS/RESULTS We found 68 AKI episodes in 52 patients in cohort 1 and 15 episodes in 12 patients in cohort 2. Diagnosis and documentation of AKI improved after guideline implementation (C1:24/68 [35%], C2: 12/15 [80%]; P = .003) as did pediatric nephrology consultation (C1:12/68 [18%]; C2: 12/15 [80%]; P < .001) and outpatient referral (C1: 3/47 [6%], C2:5/8 [63%]; P < .01). IMPLICATIONS FOR PRACTICE Neonatal AKI guideline implementation was associated with improvements in recognition, diagnosis, and inpatient and outpatient nephrology consultation. Early recognition and diagnosis along with specialist referral may improve outcomes among neonatal AKI survivors, ensuring appropriate future monitoring and long-term follow-up. IMPLICATIONS FOR RESEARCH Future research should continue to determine the long-term implications of early diagnosis of AKI and appropriate subspecialty care with follow-up.

OBJECTIVE: To investigate acute kidney injury (AKI) in neonates with a patent ductus arteriosus (PDA) including incidence, risk factors, and possible correlations between PDA-related echocardiographic measurements and AKI incidence. STUDY DESIGN: We conducted a single-center retrospective cohort study of infants admitted to the neonatal intensive care unit with a diagnosis of a PDA between July 2015 and July 2017. Infants were evaluated for development of AKI based on the KDIGO criteria and a multivariable logistic regression analysis was performed. RESULTS: A total of 142 neonates with moderate or large PDAs were included, 43 (30%) developed AKI. Patients who developed AKI had longer length of stay, lower birth weights, lengths, and gestational ages. No echocardiographic measurements were predictive of an increased risk for developing AKI. CONCLUSION: There are no significant differences in commonly measured echocardiographic markers of PDA hemodynamic significance in neonates who develop AKI.

Infections after kidney transplant in children remain a significant problem. Infections can be viral (Epstein–Barr virus, cytomegalovirus, and BK virus), bacterial (urinary tract infections, wound infections, and pneumonia), or fungal (candidiasis and Pneumocystis jirovecii , formerly Pneumocystis carinii ); all can have a significant negative impact on graft survival. Infections are typically defined as early (0–30 days posttransplant), intermediate (1–6 months posttransplant), or late (> 6 months posttransplant) depending on how far after transplant they occur. Here, we will review some of the common infections in children postkidney transplant.

Introduction The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.

There is scant literature describing the effect of glomerular disease on health-related quality of life (HRQOL). The Cure Glomerulonephropathy study (CureGN) is an international longitudinal cohort study of children and adults with four primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy). HRQOL is systematically assessed using items from the Patient-Reported Outcomes Measurement Informative System (PROMIS). We assessed the relationship between HRQOL and demographic and clinical variables in 478 children and 1115 adults at the time of enrollment into CureGN. Domains measured by PROMIS items included global assessments of health, mobility, anxiety, fatigue, and sleep impairment, as well as a derived composite measure incorporating all measured domains. Multivariable models were created that explained 7 to 32% of variance in HRQOL. Patient-reported edema consistently had the strongest and most robust association with each measured domain of HRQOL in multivariable analysis (adjusted β [95% CI] for composite PROMIS score in children, -5.2 [-7.1 to -3.4]; for composite PROMIS score in adults, -6.1 [-7.4 to -4.9]). Female sex, weight (particularly obesity), and estimated glomerular filtration rate were also associated with some, but not all, domains of HRQOL. Primary diagnosis, disease duration, and exposure to immunosuppression were not associated with HRQOL after adjustment. Sensitivity analyses and interaction testing demonstrated no significant association between disease duration or immunosuppression and any measured domain of HRQOL. Thus, patient-reported edema has a consistent negative association with HRQOL in patients with primary glomerular diseases, with substantially greater impact than other demographic and clinical variables.

There is currently no way to diagnose a rejection before a change in serum creatinine. This had led some to start doing SB, but little data exist on the utility and safety of SB in pediatric patients. There is also little known on practice patterns of pediatric nephrologists. A retrospective review of pediatric kidney transplant SB between January 2013 and January 2017 at a single center was performed. A survey went to the PedNeph email list. There were 47 SB; 15 at 6 months, 12 at 1 year, 13 at 2 years, and 7 at 3 years. There were 3 minor (1 gross hematuria and 2 hematomas) and no major complications. On 6-month SB, 1 had SC 1A ACR (6.7%) with no BR ACR. On the 12-month SB, there were 5 with SCBR ACR (41.7%) and 1 with SC AMR (8.3%). On the 2-year SB, there were 4 that had SCBR ACR (30.8%), and 1 with SC AMR (7.7%). On the 3-year SB, 1 had chronic transplant glomerulitis (14.3%). The survey showed that 34.3% of pediatric nephrologists perform SB. SB can be performed safely. By early identification of histological lesions, SB gives us an opportunity for individualized immunosuppressive regimens that may prevent chronic allograft dysfunction and improve long-term graft outcome.

We hypothesized that a standardized approach to early continuous renal replacement therapy (CRRT) during neonatal extracorporeal life support (ECLS) results in greater homogeneity of CRRT initiation times with improvements in fluid balance and outcomes. Retrospective analysis of data (2007–2015) obtained from neonates treated prior to (E1; n = 32) and after (E2; n = 31) a 2011 practice change: CRRT initiation within 48 h of ECLS. Birthweight, gestational age, ECLS mode, and age at ECLS initiation were similar to each epoch. Survival [E1: median 75%, E2: 71%] and length of ECLS [E1: median 221 h, E2: 180 h] were comparable. During E2, 100% of infants received CRRT (vs. E1: 37%; p

A range of women&rsquo, s health issues are intimately related to chronic kidney disease, yet nephrologists&rsquo, confidence in counseling or managing these issues has not been evaluated. The women&rsquo, s health working group of Cure Glomerulonephropathy (CureGN), an international prospective cohort study of glomerular disease, sought to assess adult nephrologists&rsquo, training in, exposure to, and confidence in managing women&rsquo, s health. A 25-item electronic questionnaire was disseminated in the United States (US) and Canada via CureGN and Canadian Society of Nephrology email networks and the American Society of Nephrology Kidney News. Response frequencies were summarized using descriptive statistics. Responses were compared across provider age, gender, country of practice, and years in practice using Pearson&rsquo, s chi-squared test or Fisher&rsquo, s exact test. Among 154 respondents, 53% were women, 58% practiced in the US, 77% practiced in an academic setting, and the median age was 41&ndash, 45 years. Over 65% of respondents lacked confidence in women&rsquo, s health issues, including menstrual disorders, preconception counseling, pregnancy management, and menopause. Most provided contraception or preconception counseling to less than one woman per month, on average. Only 12% had access to interdisciplinary pregnancy clinics. Finally, 89% felt that interdisciplinary guidelines and/or continuing education seminars would improve knowledge. Participants lacked confidence in both counseling and managing women&rsquo, s health. Innovative approaches are warranted to improve the care of women with kidney disease and might include the expansion of interdisciplinary clinics, the development of case-based teaching materials, and interdisciplinary treatment guidelines focused on this patient group.

Background and objectives Patients on maintenance dialysis have a higher risk of unresponsiveness to hepatitis B vaccination and loss of hepatitis B immunity. Adult guidelines recommend augmented dosing (40 mcg/dose), resulting in improved response in adults. We sought to determine whether children on dialysis mount a similar antibody response when given standard or augmented dosing of hepatitis B vaccine. Design, setting, participants, & measurements This is a retrospective review of patients on dialysis aged Results A total of 187 out of 417 patients received one or more hepatitis B vaccine boosters. The median age was 13 years; the cohort was 57% boys and 59% white. Booster dose or HBsAb titers were missing in 17 patients. Conversion to protective HBsAb titers was achieved in 135 out of 170 patients (79%) after their first single-dose booster or multidose booster series. In patients receiving a single-dose booster, the response rate was 53% (nine out of 17) after a 10 mcg dose, 86% (65 out of 76) after a 20 mcg dose, and 65% (17 out of 26) after a 40 mcg hepatitis B vaccine dose. In patients receiving a multidose booster series, the response rate was 95% (19 out of 20) after a 10 mcg/dose series, 83% (20 out of 24) after a 20 mcg/dose series, and 71% (five out of seven) after a 40 mcg/dose series. Patients receiving a multidose booster series had a response rate of 86% (44 out of 51), compared with 76% (91 out of 119) in patients receiving a single-dose booster (P=0.21). Twenty-seven patients received more than one single-dose booster or multidose series, and 26 out of 27 (96%) eventually gained immunity after receiving one to three additional single-dose boosters or multidose booster series. Conclusions There was no clear gradient of increasing seroconversion rate with increasing vaccine dose in this cohort of pediatric patients on dialysis.

PTLD of the CNS is a rare complication of solid organ transplantation, and there are only case reports/series available in the literature. Current literature suggests that CNS PTLD carries a worse prognosis than PTLD outside the CNS, and most are of B-cell lineage, predominantly monomorphic, and are associated with EBV infection. Because this disorder is so rare, there is no standard chemotherapy for pediatric patients with CNS PTLD and reported therapies for EBV-associated CNS PTLD are heterogeneous with mixed results. Since outcomes of CNS PTLD are historically poor, we attempted to develop a novel therapeutic treatment regimen. Based on a review of the literature and with the help of a multidisciplinary team, we created a regimen of chemotherapy that included dexamethasone and high-dose methotrexate in addition to intravenous and intraventricular Rituximab in two pediatric patients. The intraventricular chemotherapy succeeded in shrinking the tumor in both of our patients; however, as shown in the second case, the clinical outcome depends on the location of the tumor. Systemic and intraventricular therapies hold promise in the management of EBV-associated CNS PTLD; however the rarity of this entity prevents the development of well-designed studies necessary for the establishment of an evidence-based treatment standard.

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in the pathogenesis of several hypophosphatemic disorders. FGF23 causes hypophosphatemia by decreasing the expression of sodium phosphate cotransporters (NaPi-2a and NaPi-2c) and decreasing serum 1,25(OH)2Vitamin D3levels. We previously showed that FGFR1 is the predominant receptor for the hypophosphatemic actions of FGF23 by decreasing renal NaPi-2a and 2c expression while the receptors regulating 1,25(OH)2Vitamin D3levels remained elusive. To determine the FGFRs regulating 1,25(OH)2Vitamin D3levels, we studied FGFR3−/−FGFR4−/−mice as these mice have shortened life span and are growth retarded similar to FGF23−/−and Klotho−/−mice. Baseline serum 1,25(OH)2Vitamin D3levels were elevated in the FGFR3−/−FGFR4−/−mice compared with wild-type mice (102.2 ± 14.8 vs. 266.0 ± 34.0 pmol/l; P = 0.001) as were the serum levels of FGF23. Administration of recombinant FGF23 had no effect on serum 1,25(OH)2Vitamin D3in the FGFR3−/−FGFR4−/−mice (173.4 ± 32.7 vs. 219.7 ± 56.5 pmol/l; vehicle vs. FGF23) while it reduced serum 1,25(OH)2Vitamin D3levels in wild-type mice. Administration of FGF23 to FGFR3−/−FGFR4−/−mice resulted in a decrease in serum parathyroid hormone (PTH) levels and an increase in serum phosphorus levels mediated by increased renal phosphate reabsorption. These data indicate that FGFR3 and 4 are the receptors that regulate serum 1,25(OH)2Vitamin D3levels in response to FGF23. In addition, when 1,25(OH)2Vitamin D3levels are not affected by FGF23, as in FGFR3−/−FGFR4−/−mice, a reduction in PTH can override the effects of FGF23 on renal phosphate transport.

Prebiotics, probiotics, and synbiotics are now used more commonly in medicine, and they are generally considered to be dietary supplements and not drugs. They are not meant to be used for the treatment of disease, although recent interest has grown in the area of disease treatment. Not all of the research is in support of the benefi t provided by these supplements, and it is important to be aware of the associated risks and benefi ts. In nephrology, these supplements show potential benefi ts in treating kidney stones, uremia, and urinary tract infections. This paper reviews the current literature with an emphasis on the risks and benefi ts of these supplements in the treatment of these renal disorders.

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone that contributes to several hypophosphatemic disorders by reducing the expression of the type II sodium-phosphate cotransporters (NaPi-2a and NaPi-2c) in the kidney proximal tubule and by reducing serum 1,25-dihydroxyvitamin D3[1,25(OH)2D3] levels. The FGF receptor(s) mediating the hypophosphatemic action of FGF23 in vivo have remained elusive. In this study, we show that proximal tubules express FGFR1, −3, and −4 but not FGFR2 mRNA. To determine which of these three FGFRs mediates FGF23's hypophosphatemic actions, we characterized phosphate homeostasis in FGFR3−/−and FGFR4−/−null mice, and in conditional FGFR1−/−mice, with targeted deletion of FGFR1 expression in the metanephric mesenchyme. Basal serum phosphorus levels and renal cortical brush-border membrane (BBM) NaPi-2a and NaPi-2c expression were comparable between FGFR1−/−, FGFR3−/−, and FGFR4−/−mice and their wild-type counterparts. Administration of FGF23 to FGFR3−/−mice induced hypophosphatemia in these mice (8.0 ± 0.4 vs. 5.4 ± 0.3 mg/dl; p ≤ 0.001) and a decrease in renal BBM NaPi-2a and NaPi-2c protein expression. Similarly, in FGFR4−/−mice, administration of FGF23 caused a small but significant decrease in serum phosphorus levels (8.7 ± 0.3 vs. 7.6 ± 0.4 mg/dl; p ≤ 0.001) and in renal BBM NaPi-2a and NaPi-2c protein abundance. In contrast, injection of FGF23 into FGFR1−/−mice had no effects on serum phosphorus levels (5.6 ± 0.3 vs. 5.2 ± 0.5 mg/dl) or BBM NaPi-2a and NaPi-2c expression. These data show that FGFR1 is the predominant receptor for the hypophosphatemic action of FGF23 in vivo, with FGFR4 likely playing a minor role.

OIs present significant risks to patients following solid organ transplantation. The purpose of this study was to identify risk factors for the development of OIs after kidney transplantation in pediatric patients and to evaluate the impact of OIs on outcomes in this patient population. A single-center retrospective longitudinal cohort analysis including pediatric patients 21 yr of age or younger transplanted from July 1999 to June 2013 at an academic medical center was conducted. Patients were excluded if they received multi-organ transplant. A total of 175 patients were included in the study. Patients who developed OIs were more likely to be female and younger at the time of transplant. A six-factor risk model for OI development was developed. Death, disease recurrence, and PTLD development were similar between groups but trended toward increased incidence in the OI group. Incidence of rejection was significantly higher in the OI group (p = 0.04). Patients who developed OIs had several important risk factors, including younger age, EBV-negative serostatus, CMV donor (+)/recipient (-), biopsy-proven acute rejection, ANC1000, MMF dose500 mg/m(2), and any infection. Incidence of rejection was higher in the OI group, but rate of graft loss was not statistically different.

Studies have continued to evaluate risk factors associated with post-transplant non-adherence in pediatric patients. However, many of these studies fail to evaluate how risk factors can be utilized to predict MNA. The aims of this study were to (i) determine salient risk factors associated with MNA to develop an adequate predictive risk model and (ii) assess transplant outcomes based on the presence of MNA in a large, diverse cohort of pediatric KTX recipients. One hundred and seventy-five solitary pediatric KTX recipients transplanted from 1999 to 2013 were included. AA, males, older patients, those who lived in urban environments, had legal issues, and lived shorter distances from the transplant center were more likely to have MNA. Using logistic regression, a parsimonious model applying nine risk factors together was developed for predicting MNA, demonstrating a PPV of 69% and a NPV of 81%. Patients with MNA had more than twice the risk of biopsy proven acute rejection, 1.6 times the risk of hospitalization, and 1.8 times the risk of graft loss. Utilization of a predictive model to determine risk of MNA after pediatric KTX may offer clinicians the ability to efficiently and effectively monitor MNA following transplant.

aAMR is a potentially devastating complication of kidney transplantation. The incidence of aAMR in children, while thought to be rare, is not well defined, and there is a paucity of data on treatment regimens in children. We retrospectively reviewed the outcomes of our pediatric patients that were treated for aAMR between 2007 and 2009. Three adolescent Hispanic males were found to have aAMR. All three received deceased donor transplants, and all three verbalized non-adherence. Treatment consisted of rituximab, solumedrol, PE, and IVIgG in one patient, and PE, IVIgG, and bortezomib in two patients. The only side effect of therapy noted was mild hypotension with rituximab that resolved after decreasing the infusion rate. There were no reported infections two yr after treatment, and all of the viral monitoring in these patients remained negative.

AIE is a rare disorder in children that presents with severe diarrhea and malabsorption, caused by immune-mediated damage to intestinal mucosa. AIE is often associated with various syndromes of immunodeficiency including IPEX syndrome (immune dysregulation, polyendocrinopathy and enteropathy, X-linked). Dysfunctional T regulatory cells are the source of pathology in both IPEX syndrome and AIE as they are essential in maintaining tolerance to self-antigens and eliminating autoreactive B cells. This case report describes a 10-year-old cardiac transplant and total thymectomy patient on chronic immunosuppression with tacrolimus that presented with AIE and extraintestinal manifestations of cyclical hepatitis. Transition from tacrolimus to sirolimus successfully increased T regulatory cells and resolved enteritis and hepatitis symptoms. Data support that thymectomy at

Antibody-mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody-mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy-proven antibody-mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients. Thirty-three patients received bortezomib for antibody-mediated rejection at nine pediatric kidney transplant centers. Ninety percent of patients received intravenous immunoglobulin, 78% received plasmapheresis, and 78% received rituximab. After a median follow-up of 15 months, 65% of patients had a functioning graft. The estimated glomerular filtration rate improved or stabilized in 61% and 36% of patients at 3 and 12 months post-bortezomib, respectively. The estimated glomerular filtration rate at diagnosis significantly predicted estimated glomerular filtration rate at 12 months after adjusting for chronic histologic changes (P .001). Fifty-six percent of patients showed an at least 25% reduction in the mean fluorescence intensity of the immune-dominant donor-specific antibody, 1-3 months after the first dose of bortezomib. Non-life-threatening side effects were documented in 21 of 33 patients. Pediatric kidney transplant recipients tolerated bortezomib without life-threatening side effects. Bortezomib may stabilize estimated glomerular filtration rate for 3-6 months in pediatric kidney transplant recipients with antibody-mediated rejection.

Introduction and aim Forkhead box (FOX) proteins are a family of important transcription factors that plays important role in maintaining endothelial cells functions. The protective role of FOXO1 in multiple cellular functions is supported by several studies. In many cellular systems, the forkhead transcription factors such as FOXO1 activity is regulated by post-translational modification through phosphorylation and acetylation. The purpose of the current study was to investigate the effect of HLA class I on the phosphorylation/inactivation of the FOXO1 protein. We also investigated the impact of the HLA antibodies on the mRNA levels of the fibrosis protein LEF1. Methods Western blot analysis was used to examine the phosphorylation status of FOXO1 in human umbilical cord endothelial cells (HUVECs) after treatment with monoclonal antibodies directed against HLA class I. Real-time PCR assay was used to measure the mRNA levels of LEF1 in endothelial cells. Results Coupling of endothelial cells with monoclonal antibodies directed to HLA class I but not class II resulted in increased phosphorylation (inactivation) of the FOXO1 protein at Ser256 and Th24. In addition, the mRNA levels of FOXO1 down-stream target LEF1 were significantly up-regulated in endothelial cells treated with HLA class I antibodies compared to control treated cells. shRNAi mediated knock-down of FOXO1 protein in endothelial cells resulted in increased expression of LEF1 in endothelial cells. Conclusion This data identifies a new role of HLA antibodies in regulating endothelial cells functions by the inactivation of FOXO1 and increased its down-stream target LEF1. This data in addition to the previously published data indicating the involvement of the LEF1 in fibrosis might suggest a novel mechanism for allograft fibrosis mediated by HLA antibodies. Further studies to evaluate the in vitro findings in human allograft tissues are required.

NHE3 is the predominant Na+/H+ exchanger on the brush-border membrane (BBM) of the proximal tubule in adults. However, NHE3 null mice still have significant renal BBM Na+/H+ activity. NHE8 has been localized to the BBM of proximal tubules and is more highly expressed in neonates than adult animals. The relative role of NHE8 in adult renal H+ transport is unclear. This study examined whether there was compensation by NHE8 in NHE3−/− mice and by NHE3 in NHE8−/− mice. NHE3−/− mice had significant metabolic acidosis, and renal BBM NHE8 protein abundance was greater in NHE3−/− mice than control mice, indicating that there may be compensation by NHE8 in NHE3−/− mice. NHE8−/− mice had serum bicarbonate levels and pH that were not different from controls. NHE3 protein expression on the BBM was greater in NHE8−/− mice than in wild-type mice, indicating that there may be compensation by NHE3 in NHE8−/− mice. Both BBM NHE3 and NHE8 protein abundance increased in response to acidosis. Blood pressure and Na+/H+ exchanger activity were comparable in NHE8−/− mice to that of controls, but both were significantly lower in NHE3−/− mice compared with control mice. Compared with NHE3−/− mice, NHE3−/−/NHE8−/− mice had lower blood pressures. While serum bicarbonate was comparable in NHE3−/− mice and NHE3−/−/NHE8−/− mice, proximal tubule Na+/H+ exchange activity was less in NHE3−/−/NHE8−/− mice compared with NHE3−/− mice. In conclusion, NHE3 is the predominant Na+/H+ exchanger in adult mice. NHE8 may play a compensatory role in renal acidification and blood pressure regulation in NHE3−/− mice.

PTLD of the CNS is a rare complication of solid organ transplantation, and there are only case reports/series available in the literature. Current literature suggests that CNS PTLD carries a worse prognosis than PTLD outside the CNS, and most are of B-cell lineage, predominantly monomorphic, and are associated with EBV infection. Because this disorder is so rare, there is no standard chemotherapy for pediatric patients with CNS PTLD and reported therapies for EBV-associated CNS PTLD are heterogeneous with mixed results. Since outcomes of CNS PTLD are historically poor, we attempted to develop a novel therapeutic treatment regimen. Based on a review of the literature and with the help of a multidisciplinary team, we created a regimen of chemotherapy that included dexamethasone and high-dose methotrexate in addition to intravenous and intraventricular Rituximab in two pediatric patients. The intraventricular chemotherapy succeeded in shrinking the tumor in both of our patients; however, as shown in the second case, the clinical outcome depends on the location of the tumor. Systemic and intraventricular therapies hold promise in the management of EBV-associated CNS PTLD; however the rarity of this entity prevents the development of well-designed studies necessary for the establishment of an evidence-based treatment standard.