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Acute isolated right ventricular (RV) myocardial infarctions are relatively uncommon in clinical practice; more frequently, RV infarctions occur in association with inferior ST-segment elevation myocardial infarctions. Recent advances in diagnostic tools and methods have significantly improved our ability to detect RV infarctions in both scenarios. For this reason, it is critical for physicians to understand the pathophysiology, clinical presentation, and diagnostic criteria for RV infarctions to initiate treatment and optimize the outcomes of patients. About half of all patients with an inferior ST-segment elevation myocardial infarction develop RV infarction. In the acute setting, RV infarctions can lead to hemodynamic instability and frank shock, which are responsible for the high morbidity and mortality associated with these episodes. However, when treated properly, the prognosis of RV myocardial infarctions is quite excellent if the patient survives the acute hemodynamic compromise. In addition, RV infarctions are likely a misnomer since these events tend to represent ischemia and stunning of the RV myocardium that results in its short-term dysfunction, but the myocardium remains viable and recovers over time with no signs of an infarct if the patient survives the episode. In fact, patient outcomes in RV ischemia are dependent more on the involvement of the left ventricle than RV involvement, especially since a left ventricular infarct and dysfunction can be difficult to overcome in the long term. It is imperative to understand the various treatments available to target the hemodynamic changes and shock often seen in patients with acute RV ischemia and to implement these treatments accordingly to improve patient survival and prognosis., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research, such as small sample sizes, reliance on manual record review, and limited analytic methods, that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite, retrospective registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases, 10th Revision (ICD-10) code-defined hypertension disorder on or after January 1, 2015, and age < 19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, US Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to reduce CVD burden across the life course and establish gold-standard biomedical informatics methods for youth with hypertension disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely., Methods: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review., Results: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results., Conclusions: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

IgA vasculitis (IgAV) is a pediatric disease with skin and systemic manifestations. Here, we conducted genome, transcriptome, and proteome-wide association studies in 2,170 IgAV cases and 5,928 controls, generated IgAV-specific maps of gene expression and splicing from blood of 255 pediatric cases, and reconstructed myeloid-specific regulatory networks to define disease master regulators modulated by the newly identified disease driver genes. We observed significant association at the HLA - DRB1 (OR=1.55, P=1.1×10 -25 ) and fine-mapped specific amino-acid risk substitutions in DRβ1. We discovered two novel non-HLA loci: FCAR (OR=1.51, P=1.0×10 -20 ) encoding a myeloid IgA receptor FcαR, and INPP5D (OR=1.34, P=2.2×10 -9 ) encoding a known inhibitor of FcαR signaling. The FCAR risk locus co-localized with a cis-eQTL increasing FCAR expression; the risk alleles disrupted a PRDM1 binding motif within a myeloid enhancer of FCAR . Another risk locus was associated with a higher genetically predicted levels of plasma IL6R. The IL6R risk haplotype carried a missense variant contributing to accelerated cleavage of IL6R into a soluble form. Using systems biology approaches, we prioritized IgAV master regulators co-modulated by FCAR , INPP5D and IL6R in myeloid cells. We additionally identified 21 shared loci in a cross-phenotype analysis of IgAV with IgA nephropathy, including novel loci PAID4, WLS , and ANKRD55 .

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that can affect multiple organ systems and is heterogenous in its presentation and response to therapy. When diagnosed in childhood, SLE is associated with increased morbidity and mortality compared to adult SLE, often requiring substantial immunosuppression with the risk of significant side effects. There remains a significant unmet need for new therapies that can improve disease control and reduce glucocorticoid and other toxic medication exposure for patients with severe or refractory disease. The pathogenesis of SLE involves B cell dysregulation and autoantibody production, which are a hallmark of the disease. Currently approved B cell directed therapies often result in incomplete B cell depletion and may not target long-lived plasma cells responsible for SLE autoantibodies. It is hypothesized that by persistently eliminating both B cells and plasmablasts, CAR T therapy can halt autoimmunity and prevent organ damage in patient's refractory to current B cell-depleting treatments. Herein we summarize the current preclinical and clinical data utilizing CAR T cells for SLE and discuss the future of this treatment modality for lupus., (© 2024. The Author(s).)

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 <20 mL/min/1.73 m 2 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 <30 m/min/1.73 m 2 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., (© 2024 Wiley Periodicals LLC.)

Objective: To describe the blood pressure outcomes of infants admitted to the neonatal intensive care unit (NICU) with idiopathic (nonsecondary) hypertension (HTN) who were discharged on antihypertensive therapy., Study Design: Retrospective, multicenter study of 14 centers within the Pediatric Nephrology Research Consortium. We included all infants with a diagnosis of idiopathic HTN discharged from the NICU on antihypertensive treatment. The primary outcome was time to discontinuation of antihypertensive therapy, grouped into (≤6 months, >6 months to 1 year, and >1 year). Comparisons between groups were made with χ 2 tests, Fisher's exact tests, and ANOVA., Results: Data from 118 infants (66% male) were included. Calcium channel blockers were the most prescribed class of antihypertensives (56%) in the cohort. The percentages remaining on antihypertensives after NICU discharge were 60% at 6 months, 26% at 1 year, and 7% at 2 years. Antenatal steroid treatment was associated with decreased likelihood of antihypertensive therapy >1 year after discharge., Conclusions: This multicenter study reports that most infants admitted to the NICU diagnosed with idiopathic HTN will discontinue antihypertensive treatment by 2 years after NICU discharge. These data provide important insights into the outcome of neonatal HTN, but should be confirmed prospectively., Competing Interests: Declaration of Competing Interest M.S. was supported by the National Institute of Diabetes and Digestive and Kidney DiseasesT32DK007662 and National Center for Advancing Translational Sciences, Grant numbers: K12TR004415. The funding sources for this study had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: Acute kidney injury (AKI) in children has serious short-term and long-term consequences. We sought 1) to prospectively describe NSAID-associated AKI in hospitalized children; 2) to determine if NSAID-associated AKI was more severe in younger children < 5 years; and 3) to follow outcomes after hospitalization for NSAID-associated AKI., Methods: This was a prospective, multi-center study in hospitalized children 1 month to 18 years. Parents/guardians were given a brief questionnaire to determine the dosing, duration, and type of NSAIDs given. Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria were used to stage AKI severity. Patients with other causes of AKI were excluded (e.g., other nephrotoxins, sepsis, malignancy, etc.)., Results: We identified 25 patients with NSAID-associated AKI, accounting for 3.1% of AKI. All 25 had AKI upon hospital presentation. The median age was 15.5 years, and 20/25 (80%) had volume depletion. Median duration of NSAID use was 2 days, and 63% of patients took the normal recommended NSAID dose. Median hospital length of stay was 4 days, and none required dialysis. At the most recent estimated glomerular filtration rate (eGFR) after discharge (available in 17/25 patients), only 4/17 (24%) had eGFR ≥ 90 ml/min/1.73 m 2 , and 13/17 (76%) had eGFR 60 to < 90 ml/min/1.73 m 2 , indicative of abnormal kidney function., Conclusions: NSAID-associated AKI usually occurs with recommended NSAID dosing in the setting of dehydration. Follow-up after AKI showed a substantial rate of CKD. Therefore, we recommend that NSAIDs should not be used in dehydrated children. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. Here we performed a genome-wide association study of 10,146 kidney-biopsy-diagnosed IgAN cases and 28,751 controls across 17 international cohorts. We defined 30 genome-wide significant risk loci explaining 11% of disease risk. A total of 16 loci were new, including TNFSF4/TNFSF18, REL, CD28, PF4V1, LY86, LYN, ANXA3, TNFSF8/TNFSF15, REEP3, ZMIZ1, OVOL1/RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The risk loci were enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice. We also observed a positive genetic correlation between IgAN and serum IgA levels. High polygenic score for IgAN was associated with earlier onset of kidney failure. In a comprehensive functional annotation analysis of candidate causal genes, we observed convergence of biological candidates on a common set of inflammatory signaling pathways and cytokine ligand-receptor pairs, prioritizing potential new drug targets., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Rationale & Objective: Adolescent- and adult-onset minimal change disease (MCD) may have a clinical course distinct from childhood-onset disease. We characterized the course of children and adults with MCD in the Cure Glomerulonephropathy Network (CureGN) and assessed predictors of rituximab response., Study Design: Prospective, multicenter, observational study., Study Participants: CureGN participants with proven MCD on biopsy., Exposure: Age at disease onset, initiation of renin-angiotensin-aldosterone system (RAAS) blockade, and immunosuppression including rituximab during the study period., Outcome: Relapse and remission, change in estimated glomerular filtration rate (eGFR), and kidney failure., Analytical Approach: Remission and relapse probabilities were estimated using Kaplan-Meier curves and gap time recurrent event models. Linear regression models were used for the outcome of change in eGFR. Cox proportional hazards models were used to estimate the association between rituximab administration and remission., Results: The study included 304 childhood- (≤12 years old), 49 adolescent- (13-17 years old), and 201 adult- (≥18 years) onset participants with 2.7-3.2 years of follow-up after enrollment. Children had a longer time to biopsy (238 vs 23 and 36 days in adolescent- and adult-onset participants, respectively; P<0.001) and were more likely to have received therapy before biopsy. Children were more likely to be treated with immunosuppression but not RAAS blockade. The rate of relapse was higher in childhood- versus adult-onset participants (HR, 1.69 [95% CI, 1.29-2.21]). The probability of remission was also higher in childhood-onset disease (HR, 1.33 [95%CI, 1.02-1.72]). In all groups eGFR loss was minimal. Children were more likely to remit after rituximab than those with adolescent- or adult-onset disease (adjusted HR, 2.1; P=0.003). Across all groups, glucocorticoid sensitivity was associated with a greater likelihood of achieving complete remission after rituximab (adjusted HR, 2.62; P=0.002)., Limitations: CureGN was limited to biopsy-proven disease. Comparisons of childhood to nonchildhood cases of MCD may be subject to selection bias, given that childhood cases who undergo a biopsy may be limited to patients who are least responsive to initial therapy., Conclusions: Among patients with MCD who underwent kidney biopsy, there were differences in the course (relapse and remission) of childhood-onset compared with adolescent- and adult-onset disease, as well as rituximab response., Plain-Language Summary: Minimal change disease is a biopsy diagnosis for nephrotic syndrome. It is diagnosed in childhood, adolescence, or adulthood. Patients and clinicians often have questions about what to expect in the disease course and how to plan therapies. We analyzed a group of patients followed longitudinally as part of the Cure Glomerulonephropathy Network (CureGN) and describe the differences in disease (relapse and remission) based on the age of onset. We also analyzed rituximab response. We found that those with childhood-onset disease had a higher rate of relapse but also have a higher probability of reaching remission when compared with adolescent- or adult-onset disease. Children and all steroid-responsive patients are more likely to achieve remission after rituximab., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited., Methods: A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure., Results: Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe (> 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score > 4 on kidney biopsy were associated with kidney failure., Conclusions: Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: FSGS is a heterogeneous diagnosis with a guarded prognosis. Polymorphisms in the apolipoprotein L1 ( APOL1 ) gene are associated with developing FSGS and faster progression to kidney failure in affected patients. Better understanding the natural history of patients with FSGS and APOL1 risk alleles is essential to improve patient care and support the design and interpretation of interventional studies. The objective of this study was to evaluate the quantitative association between APOL1 and kidney disease progression and the interaction with other clinical and laboratory factors., Methods: CureGN cohort study participants with biopsy diagnosis of FSGS, regardless of self-identified race, were included. The exposure of interest was two APOL1 risk alleles (high risk) versus zero to one risk alleles (low risk). The primary outcome was eGFR slope categorized as rapid progressor (eGFR slope ≤-5 ml/min per year), intermediate progressor (slope between 0 and -5), or nonprogressor (slope ≥0). Multivariable ordinal logistic and linear regressions were used for adjusted analyses. Missing data were addressed using multiple imputation., Results: Of 650 participants, 476 (73%) had genetic testing, among whom 87 (18%) were high risk. High-risk participants were more likely to have lower median eGFR (62 [interquartile range, 36-81] versus low-risk participants 76 ml/min per 1.73 m 2 [interquartile range, 44-106]; P <0.01). In adjusted analysis, the odds of more rapid progression of eGFR was 2.75 times higher (95% confidence interval, 1.67 to 4.53; P <0.001) in the high-risk versus low-risk groups., Conclusions: In patients with FSGS, high-risk APOL1 genotype is the predominant factor associated with more rapid loss of kidney function., (Copyright © 2023 by the American Society of Nephrology.)

Background: 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., Methods: 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., Results: 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 m 2 /min (IQR - 51 to + 8) at 1 year and - 3 mL/min/1.73 m 2 /year (IQR - 19 to + 6) at latest follow-up. We found no difference in kidney failure at the proposed < 25% and 25-50% cellular crescents thresholds, and thus added a new provisional threshold of 10% that better predicted outcomes in children. Moreover, use of 10% and 25% thresholds for fibrous crescents showed a fourfold and sevenfold increase in risk of kidney failure., Conclusions: In 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., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: IgA vasculitis (IgAV) is the most common type of vasculitis in children. There is a lack of consensus for management of significant IgAV nephritis (IgAVN). This study was designed to identify the most used treatment options and describe their efficacy., Methods: This is a multicenter retrospective study of children age 1-21 years with IgAVN who were managed for at least 6 months by a nephrologist. Subjects with at least microscopic hematuria and proteinuria and/or decreased kidney function were enrolled. Kidney outcome was assessed by eGFR and urine protein/creatinine (UPC) ratios at 2-4 weeks, 3, 6, and 12 months post-diagnosis., Results: A total of 128 subjects with median age of 7 years (range 2-18) were included. Of these, 69 subjects had kidney biopsy with crescents detected in 53%. AKI (P = 0.039), nephrosis (P = 0.038), and crescents on biopsy (P = 0.013) were more likely in older patients. Patients with UPC > 1 mg/mg were more likely to get a kidney biopsy (P < 0.001) and to be treated with steroids ± immunosuppressive (IS) agents (P = 0.001). Sixty-six percent of patients were treated with steroids and/or IS agents for variable durations. Anti-metabolite agents were the most common IS agents used with variability in dosing and duration. At 12 months, most subjects had a normal eGFR (79%) (median 123, range 68-207 mL/min/1.73 m 2 ) and no proteinuria (median UPC 0.15, range 0.01-4.02 mg/mg)., Conclusions: IS agents are frequently used in managing IgAVN associated with heavy proteinuria, nephrosis, and/or AKI. Prospective studies are needed to determine indications and needed duration of IS therapy. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background and Objectives: Nephrotic syndrome (NS) in the first year of life is called congenital (CNS) if diagnosed between 0-3 months, or infantile (INS) if diagnosed between 3-12 months of age. The aim of this study was to determine if there were clinically meaningful differences between CNS and INS patients, regarding clinical presentation, management and outcomes., Design Setting Participants and Measurements: Eleven Pediatric Nephrology Research Consortium sites participated in the study, using IRB-approved retrospective chart reviews of CNS and INS patients born between 1998 and 2019. Data were collected on patient characteristics, pertinent laboratory tests, provided therapy, timing of unilateral/bilateral nephrectomy and initiation of renal replacement therapy (RRT)., Results: The study included 69 patients, 49 with CNS and 20 with INS, with a median age at diagnosis of 1 and 6 months, respectively. Management for the two groups was similar regarding nutrition, thyroxin supplementation, immunoglobulin administration, and thrombosis prophylaxis. Within the first 2 months after diagnosis, daily albumin infusions were used more often in CNS vs . INS patients (79 vs . 30%; p = 0.006), while weekly infusions were more common in INS patients (INS vs . CNS: 50 vs . 3%; p = 0.001). During the 6 months preceding RRT, albumin infusions were more frequently prescribed in CNS vs . INS (51 vs . 15%; p = 0.007). Nephrectomy was performed more often in CNS (78%) than in INS (50%; p = 0.02). End-stage kidney disease tended to be more common in children with CNS (80%) vs . INS (60%; p = 0.09)., Conclusion: Compared to INS, patients with CNS had a more severe disease course, requiring more frequent albumin infusions, and earlier nephrectomy and RRT. Despite center-specific variations in patient care, 20-40% of these patients did not require nephrectomy or RRT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Constantinescu, Mattoo, Smoyer, Greenbaum, Niu, Howard, Muff-Luett, Benoit, Traum, Annaim, Wenderfer, Plautz, Rheault, Myette, Twombley, Kamigaki, Wandique-Rapalo, Kallash and Vasylyeva.)

Introduction: IgA nephropathy (IgAN) differs from other glomerular diseases by the frequently predominant lambda over kappa light chain deposition. Using the Cure Glomerulonephropathy (CureGN) IgAN cohort, we aimed to determine whether predominant lambda chain deposition is associated with worse clinical outcomes or histopathologic markers of more active disease., Methods: Patients were categorized based on the intensity of light chain staining. The lambda dominant (LD) group was defined by a difference in intensity score of lambda minus kappa ≥ 1+ and the kappa-lambda codominant (KL) group by a difference < 1+. We compared the clinical course of patients in each category from the time of kidney biopsy and time of enrollment into CureGN to the time of remission (proteinuria < 0.3 g/g), 50% reduction in estimated glomerular filtration rate (eGFR), or progression to end-stage kidney disease (ESKD). We also analyzed differences in histopathologic characteristics between the 2 groups., Results: Among 440 patients, we found no significant differences between groups in baseline clinical characteristics nor in rates of remission, 50% reduction in eGFR, or progression to ESKD. Patients in the LD group had a modestly greater frequency of IgG staining ≥ 1+. The biopsy results of 234 patients reviewed by CureGN pathologists revealed a greater frequency of endocapillary hypercellularity (51.1% vs. 36.3%, P  = 0.04) in the LD group, but no other significant difference in histopathologic features., Conclusion: In IgAN, we found an association between lambda predominance and increased endocapillary hypercellularity, but no association with clinical outcomes., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Objectives: To determine whether youth with white coat hypertension on initial ambulatory blood pressure monitoring (ABPM) continue to demonstrate the same pattern on repeat ABPM., Study Design: Retrospective longitudinal cohort study of patients referred for high blood pressure (BP) and diagnosed with white coat hypertension by ABPM who had follow-up ABPM 0.5-4.6 years later at 11 centers in the Pediatric Nephrology Research Consortium. We classified ABPM phenotype using the American Heart Association guidelines. At baseline, we classified those with hypertensive BP in the clinic as "stable white coat hypertension," and those with normal BP as "intermittent white coat hypertension." We used multivariable generalized linear mixed effect models to estimate the association of baseline characteristics with abnormal ABPM phenotype progression., Results: Eighty-nine patients met the inclusion criteria (median age, 13.9 years; 78% male). Median interval time between ABPM measurements was 14 months. On follow-up ABPM, 61% progressed to an abnormal ABPM phenotype (23% ambulatory hypertension, 38% ambulatory prehypertension). Individuals age 12-17 years and those with stable white coat hypertension had greater proportions progressing to either prehypertension or ambulatory hypertension. In the multivariable models, baseline wake systolic BP index ≥0.9 was significantly associated with higher odds of progressing to ambulatory hypertension (OR 3.07, 95% CI 1.02-9.23)., Conclusions: The majority of the patients with white coat hypertension progressed to an abnormal ABPM phenotype. This study supports the 2017 American Academy of Pediatrics Clinical Practice Guideline's recommendation for follow-up of ABPM in patients with white coat hypertension., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pediatric hypertension (HTN) is a significant and growing health concern. While previously thought to be an uncommon condition in the pediatric population, recent studies have shown an increase in incidence, which is largely due to the obesity epidemic. Accordingly, primary or idiopathic HTN has become more prevalent compared to secondary causes of HTN. The incidence of hypertension is about 3.5%; however, it may be higher as HTN can be missed during routine pediatric well visits. Since childhood HTN frequently tracks into adulthood and is a risk factor for both cardiovascular disease and progression of renal disease; early diagnosis and management of this condition is essential. In this review, we will discuss the approach of a pediatric nephrologist for evaluation and management of pediatric HTN., (© 2020 Publishing services provided by Elsevier B.V. on behalf of King Faisal Specialist Hospital & Research Centre (General Organization), Saudi Arabia.)

Background and Objectives: Performing adequately powered clinical trials in pediatric diseases, such as SLE, is challenging. Improved recruitment strategies are needed for identifying patients., Design, Setting, Participants, & Measurements: Electronic health record algorithms were developed and tested to identify children with SLE both with and without lupus nephritis. We used single-center electronic health record data to develop computable phenotypes composed of diagnosis, medication, procedure, and utilization codes. These were evaluated iteratively against a manually assembled database of patients with SLE. The highest-performing phenotypes were then evaluated across institutions in PEDSnet, a national health care systems network of >6.7 million children. Reviewers blinded to case status used standardized forms to review random samples of cases ( n =350) and noncases ( n =350)., Results: Final algorithms consisted of both utilization and diagnostic criteria. For both, utilization criteria included two or more in-person visits with nephrology or rheumatology and ≥60 days follow-up. SLE diagnostic criteria included absence of neonatal lupus, one or more hydroxychloroquine exposures, and either three or more qualifying diagnosis codes separated by ≥30 days or one or more diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 100% (95% confidence interval [95% CI], 99 to 100), specificity was 92% (95% CI, 88 to 94), positive predictive value was 91% (95% CI, 87 to 94), and negative predictive value was 100% (95% CI, 99 to 100). Lupus nephritis diagnostic criteria included either three or more qualifying lupus nephritis diagnosis codes (or SLE codes on the same day as glomerular/kidney codes) separated by ≥30 days or one or more SLE diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 90% (95% CI, 85 to 94), specificity was 93% (95% CI, 89 to 97), positive predictive value was 94% (95% CI, 89 to 97), and negative predictive value was 90% (95% CI, 84 to 94). Algorithms identified 1508 children with SLE at PEDSnet institutions (537 with lupus nephritis), 809 of whom were seen in the past 12 months., Conclusions: Electronic health record-based algorithms for SLE and lupus nephritis demonstrated excellent classification accuracy across PEDSnet institutions., (Copyright © 2022 by the American Society of Nephrology.)

The prevalence of hypertension is increasing in pediatric populations. While clinical data and practice guidelines identify the impact of hypertension on organ dysfunction and emphasize the importance for end-organ damage screening, the bidirectional effects of pediatric hypertension on neurocognitive and psychological outcomes are understudied. The objective of this review is to highlight the association between hypertension and cognition, attention, learning, and mental health in children and adolescents. In doing so, this review provides a framework and toolkit to integrate neuropsychology and psychology into the screening and management stages of pediatric hypertension. By recognizing the effects of hypertension on cognition, behavior, and mental health, screenings and interventions can be implemented to proactively and comprehensively improve the health outcomes for children with blood pressure concerns., (© 2021. IPNA.)

Background: Eculizumab is approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use off-label is frequently reported. The aim of this study was to describe the broader use and outcomes of a cohort of pediatric patients exposed to eculizumab., Methods: A retrospective, cohort analysis was performed on the clinical and biomarker characteristics of eculizumab-exposed patients < 25 years of age seen across 21 centers of the Pediatric Nephrology Research Consortium. Patients were included if they received at least one dose of eculizumab between 2008 and 2015. Traditional summary statistics were applied to demographic and clinical data., Results: A total of 152 patients were identified, mean age 9.1 (+/-6.8) years. Eculizumab was used "off-label" in 44% of cases. The most common diagnoses were aHUS (47.4%), Shiga toxin-producing Escherichia coli HUS (12%), unspecified thrombotic microangiopathies (9%), and glomerulonephritis (9%). Genetic testing was available for 60% of patients; 20% had gene variants. Dosing regimens were variable. Kidney outcomes tended to vary according to diagnosis. Infectious adverse events were the most common adverse event (33.5%). No cases of meningitis were reported. Nine patients died of noninfectious causes while on therapy., Conclusions: This multi-center retrospective cohort analysis indicates that a significant number of children and young adults are being exposed to C5 blockade for off-label indications. Dosing schedules were highly variable, limiting outcome conclusions. Attributable adverse events appeared to be low. Cohort mortality (6.6%) was not insignificant. Prospective studies in homogenous disease cohorts are needed to support the role of C5 blockade in kidney outcomes.

Edema is the abnormal accumulation of fluid in the interstitial compartment of tissues within the body. In nephrotic syndrome, edema is often seen in dependent areas such as the legs, but it can progress to cause significant accumulation in other areas leading to pulmonary edema, ascites, and/or anasarca. In this review, we focus on mechanisms and management of edema in children with nephrotic syndrome. We review the common mechanisms of edema, its burden in pediatric patients, and then present our approach and algorithm for management of edema in pediatric patients. The extensive body of experience accumulated over the last 5 decades means that there are many options, and clinicians may choose among these options based on their experience and careful monitoring of responses in individual patients.

Background: Acute tubulointerstitial nephritis (TIN) is a significant cause of acute renal failure in paediatric and adult patients. There are no large paediatric series focusing on the aetiology, treatment and courses of acute TIN., Patients, Design and Setting: We collected retrospective clinical data from paediatric patients with acute biopsy-proven TIN by means of an online survey. Members of four professional societies were invited to participate., Results: Thirty-nine physicians from 18 countries responded. 171 patients with acute TIN were included (54% female, median age 12 years). The most frequent causes were tubulointerstitial nephritis and uveitis syndrome in 31% and drug-induced TIN in 30% (the majority of these caused by non-steroidal anti-inflammatory drugs). In 28% of patients, no initiating noxae were identified (idiopathic TIN). Median estimated glomerular filtration rate (eGFR) rose significantly from 31 at time of renal biopsy to 86 mL/min/1.73 m 2 3-6 months later (p<0.001). After 3-6 months, eGFR normalised in 41% of patients (eGFR ≥90 mL/min/1.73 m 2 ), with only 3% having severe or end-stage impairment of renal function (<30 mL/min/1.73 m 2 ). 80% of patients received corticosteroid therapy. Median eGFR after 3-6 months did not differ between steroid-treated and steroid-untreated patients. Other immunosuppressants were used in 18% (n=31) of patients, 21 of whom received mycophenolate mofetil., Conclusions: Despite different aetiologies, acute paediatric TIN had a favourable outcome overall with 88% of patients showing no or mild impairment of eGFR after 3-6 months. Prospective randomised controlled trials are needed to evaluate the efficacy of glucocorticoid treatment in paediatric patients with acute TIN., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Diabetic nephropathy (DN) is one of the most common microvascular complications in type 1 diabetes Mellitus (T1D). Urinary markers of renal damage or oxidative stress may signal early stages of DN. The association of these markers with blood pressure (BP) patterns and glycemic variability (GV) in children is yet to be explored., Methods: Subjects between the ages of 10 and 21 years with T1D were enrolled. Continuous glucose monitoring (CGM) and ambulatory blood pressure monitoring (ABPM) were performed on each subject. Urine samples were collected and analyzed for albumin, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) and pentosidine., Results: The study included 21 subjects (62% female) with median age of 16.8 (IQR: 14.5, 18.9). Median HbA1C was 8.4 (IQR: 7.5, 9.3). While microalbuminuria was negative in all but one case (4.8%), urinary NGAL/Cr and pentosidine/Cr ratios were significantly elevated (P<0.001) in diabetic patients despite having normal microalbuminuria, and they correlated significantly with level of microalbumin/Cr (r=0.56 [CI: 0.17, 0.8] and r=0.79 [CI: 0.54, 0.91], respectively). Using ABPM, none had hypertension, however, poor nocturnal systolic BP dipping was found in 48% of cases (95% CI: 28-68%). Urinary NGAL/Cr negatively correlated with nocturnal SBP dipping (r=-0.47, CI: -0.76, -0.03). Urine NGAL/Cr also showed a significant negative correlation with HbA1c measurements, mean blood glucose, and high blood glucose index (r=-0.51 [CI: -0.78, -0.09], r=-0.45 [CI: -0.74, -0.03], and r=-0.51 [CI: -0.77, -0.1], respectively). Median urinary NGAL/Cr and pentosidine/Cr ratios were higher in the high GV group but were not significantly different., Discussion: This pilot study explores the role of ABPM and urinary markers of tubular health and oxidative stress in early detection of diabetic nephropathy. GV may play a role in the process of this diabetic complication., Competing Interests: Author LuM has received research grants from Novo Nordisk, Astrazeneca, Sanofi Aventis, and from Juvenile Diabetes Research Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mamilly, Mastrandrea, Mosquera Vasquez, Klamer, Kallash and Aldughiem.)

Background: Children with nephrotic syndrome (NS) are at high risk for vaccine-preventable infections due to the immunological effects from the disease and concurrent treatment with immunosuppressive medications. Immunizations in these patients may be deferred due to their immunosuppressive treatment which may increase the risk for vaccine-preventable infections. Immunization practices in children with NS continue to vary among pediatric nephrologists. This raises the question of whether children with NS are receiving the recommended vaccinations at appropriate times. Therefore, it is critical to understand the practices and patient education provided by physicians to patients on the topic of vaccinations. Methods: After informed consent, parents/guardians of 153 pediatric patients (<18 years old) diagnosed with NS from 2005 to 2018 and 50 pediatric nephrologists from 11 participating centers completed anonymous surveys to evaluate immunization practices among pediatric nephrologists, assess the vaccine education provided to families of children with NS, assess the parental knowledge of immunization recommendations, and assess predictors of polysaccharide pneumococcal vaccine adherence. The Advisory Committee on Immunization Practices (ACIP) Immunization 2019 Guideline for those with altered immunocompetence was used to determine accuracy of vaccine knowledge and practices. Results: Forty-four percent of providers self-reported adherence to the ACIP guidelines for inactive vaccines and 22% to the guidelines for live vaccines. Thirty-two percent of parents/guardians reported knowledge that aligned with the ACIP guidelines for inactive vaccines and 1% for live vaccines. Subjects residing in the Midwest and provider recommendations for vaccines were positive predictors of vaccine adherence ( p < 0.001 and p 0.02, respectively). Conclusions: Vaccine recommendation by medical providers is paramount in vaccine adherence among pediatric patients with NS. This study identifies potential educational opportunities for medical subspecialty providers and family caregivers about immunization recommendations for immunosuppressed patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tran, Selewski, Oh, Troost, Massengill, Al-Akash, Mahesh, Amin, Ashoor, Chanchlani, Kallash, Woroniecki and Gipson.)

Background: Ambulatory blood pressure monitoring (ABPM) measures mean arterial pressure (MAP) then extrapolates systolic and diastolic blood pressure (BP) values. Pediatric guidelines recommend using calculated systolic and diastolic BP rather than measured MAP for diagnosis of ambulatory hypertension (HTN). The 95th percentile BP that defines ambulatory HTN is higher in some children than thresholds used to define ambulatory HTN in adults., Methods: This is a retrospective study of patients who underwent 24-h ABPM. The level of agreement in ambulatory HTN diagnosis using MAP vs. systolic/diastolic BP was evaluated using Cohen's kappa coefficient. Similar analysis was done to assess agreement in HTN diagnosis using adult vs. pediatric criteria for males taller than 165 cm., Results: A total of 263 ABPM studies were included. There was good agreement for diagnosis of HTN using MAP or systolic/diastolic BP (k = 0.75; 95% CI: 0.67-0.83). However, there was disagreement between the methods in 12% (n = 31) of subjects. Similarly, there was good agreement (k = 0.70; 95% CI: 0.56-0.85) between pediatric and adult criteria for HTN diagnosis. Nineteen patients were found to be hypertensive (9 using MAP criteria, 10 using adult criteria) who would not have met ambulatory HTN criteria using current pediatric guidelines., Conclusions: Inclusion of MAP along with systolic and diastolic BP in ABPM analysis alongside using adult criteria for diagnosing HTN in male children ≥ 165 cm may improve accuracy of pediatric HTN diagnosis and reduce false negative rate. Larger studies are needed to assess the clinical validity of these results. Graphical abstract.

Best treatments for initial presentation and relapses in children with nephrotic syndrome (NS) are still to be defined. The PROPINE study, published in this issue of Kidney International, demonstrates for relapse of childhood NS, the non-inferiority of a short taper (over 36 days) after remission with steroids. This study reinforces the need for more well-designed studies and the incorporation of predictive biomarkers, genetic studies, and other details to personalize treatment for each child with idiopathic NS., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Persistent isolated microscopic hematuria is relatively common in pediatric practice, affecting around 0.25% of children. Isolated microscopic hematuria can be caused by a myriad of potentially benign or serious causes, including urologic issues; kidney stones; glomerular diseases, including disorders of the glomerular basement membrane; hematologic abnormalities; and others. The challenge for the pediatrician or pediatric nephrologist is to distinguish children with potentially progressive forms of kidney disease versus other causes while minimizing cost and inconvenience for the child and family. This manuscript will review the multiple potential causes of microscopic hematuria and provide a framework for the initial evaluation and monitoring of such patients., Competing Interests: All authors have nothing to disclose., (Copyright © 2020 by the American Society of Nephrology.)

Background: IUGR has been associated with nephron loss and chronic kidney disease (CKD)., Materials and Methods: We examined autophagy and apoptosis markers in the kidneys of IUGR Sprague Dawley rats induced by maternal low protein diet (LP), comparing them to controls. The autophagy marker LC3B, the pro-apoptotic protein Bax, and the anti-apoptotic protein Bcl-2 were determined by quantitative immunoblotting. Immunohistochemical expressions of LC3B, Bax, and Bcl-2 were evaluated at 4 weeks age. Glomerular counts (by maceration techniques) were performed at 5 weeks., Results: The LP diet offspring were lighter (P < 0.05). In IUGR kidneys, LC3B and Bax were increased at birth (p < 0.05, p < 0.001) and at 4 weeks (p < 0.0142, p < 0.0001), Bcl-2 was decreased at birth (p < 0.05), and there were less glomeruli (p < 0.01) at 5 weeks., Conclusions: Autophagy and apoptosis may have a role in IUGR associated decreased nephron number in Sprague rats.

Childhood nephrotic syndrome is a challenging and often persistent renal disorder, and its incidence varies between different ethnicities and regions. Corticosteroids have been the main treatment for decades and are effective in most children with idiopathic NS, although 10-15% of these children become steroid resistant. Furthermore, some initially steroid sensitive children follow a steroid dependent or frequently relapsing course and are therefore at increased risk for developing steroid toxicity. In such children, alternative immunosuppressive medications are used to induce and/or maintain remission of NS. One such drug, rituximab, is a monoclonal antibody directed against the B lymphocyte CD20 marker which induces depletion of B cells, and has shown promising results in the management of NS in children. In this review, we summarize recent studies on the efficacy and safety of rituximab in the different types of childhood nephrotic syndrome, the known and potential mechanisms of action of rituximab, its possible complications and side effects, and the available and potential biomarkers of rituximab activity.

Background: Nephrotic syndrome (NS) results in hypercoagulability and increased risk of infection. Furthermore, infection increases the risk of venous thromboembolism (VTE). Our objective was to determine the prevalence of infection, VTE, and the associated outcomes among a cohort of hospitalized children with NS., Methods: All children with NS admitted to 17 pediatric hospitals across North America from 2010 to 2012 were included. Prevalence of infection and VTE was determined. Wilcoxon rank-sum and logistic regression were performed., Results: Seven-hundred thirty hospitalizations occurred among 370 children with NS. One-hundred forty-eight children (40%) had ≥ 1 infection (211 episodes) and 11 (3%) had VTE. Those with VTE had infection more frequently (p = 0.046) and were younger at NS diagnosis (3.0 vs. 4.0 years; p = 0.008). The most common infectious pathogen identified was Streptococcus pneumoniae. The median hospital length of stay for those with infection [10 vs 5 days (p < 0.0001)] or VTE [22 vs 6 days (p < 0.0001)] was longer than those without either complication. Of those with infection, 13% had an intensive care unit (ICU) stay compared with 3.3% of those without infection. Median ICU stay was 4 days in those with VTE compared to 0 days in those without (p < 0.001). By logistic regression, only the number of ICU days was associated with VTE (OR 1.074, 95% CI 1.013-1.138)., Conclusions: Hospitalized children with NS have high rates of infection. Presence of VTE was associated with infection. Both were associated with longer hospitalizations and ICU stays.

Background and Objectives: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence., Methods: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence., Results: We analyzed 158 patients; 64 (41%) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78% of patients with LSRNS compared to 39% of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76% recurrence rate compared with a 40% recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95% CI 5.6; 1.3-23.7) compared to FSGS predicted disease recurrence., Conclusions: Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence.

Background: Few data exist for the genetic variants underlying the risk for steroid-sensitive nephrotic syndrome (SSNS) in children. The objectives of this study were to evaluate HLA-DQA1 and APOL1 variants as risk factors for SSNS in African American children and use classic HLA antigen types and amino acid inference to refine the HLA-DQA1 association., Study Design: Case-control study., Setting & Participants: African American children with SSNS or steroid-resistant nephrotic syndrome (SRNS) were enrolled from Duke University and centers participating in the Midwest Pediatric Nephrology Consortium., Factor: Genetic variants in HLA-DQA1 (C34Y [rs1129740]; F41S [rs1071630]) and APOL1 high-risk alleles., Outcomes: SSNS and SRNS., Measurements: Direct sequencing for the HLA-DQA1 and APOL1 variants in 115 African American children (65 with SSNS and 50 with SRNS). Imputation of classic HLA alleles and amino acids was done in 363 South Asian children., Results: The 2 HLA-DQA1 variants were significantly associated with SSNS in African American children (C34Y: P=5.7 × 10 -11 ; OR, 3.53; 95% CI, 2.33-5.42; F41S: P=1.2 × 10 -13 ; OR, 4.08; 95% CI, 2.70-6.28), but not with SRNS (C34Y: P=0.6; F41S: P=0.2). APOL1 high-risk variants were not associated with SSNS (P=0.5) but showed significant associations with SRNS (P=1.04 × 10 -7 ; OR, 4.17; 95% CI, 2.23-7.64). HLA-DQA1*0201, HLA-DQB1*0201, and HLA-DRB1*0701 were the classic HLA alleles with the most significant associations with SSNS risk. The most significantly associated amino acid positions were HLA-DQα1 56 and 76 (both P=2.8 × 10 -7 ). Conditional analysis revealed that these variants most likely account for the observed association., Limitations: Modest sample size and limited statistical power to detect small to moderate effect sizes. Children studied may not be representative of all African American children in the United States., Conclusions: HLA-DQA1 is a risk locus for SSNS, but not SRNS, in African American children, consistent with its role in SSNS risk in children of European, Asian, and African ancestries. There is little evidence of a significant role for the APOL1 high-risk alleles in childhood SSNS in African American children. Refinement of the HLA-DQA1 association identified the critical classic HLA antigen types and amino acids of the HLA-DQ α1 molecule., (Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.)

Background: Rituximab (RTX) is increasingly being used in place of calcineurin inhibitors (CNI) in pediatric patients with steroid-dependent nephrotic syndrome (SDNS). However, despite its favorable safety profile, its unit cost is prohibitive. We therefore compared the healthcare costs associated with the use of both agents in a retrospective cohort., Methods: This study was a retrospective analysis of data retrieved from the medical charts and electronic databases of pediatric patients (age range 2-18 years) with SDNS who were treated with either CNI or RTX from January 2008 to December 2012 at Children's Hospital of New Orleans, Louisiana. The minimum follow-up period was 12 months., Results: Of the 18 patients whose medical data were analyzed, ten received RTX and eight were treated with CNI. The annualized healthcare cost for the rituximab group was $197,031 versus $189,857 (all values in US dollars) for the CNI group (p > 0.05). At the 12-month follow-up, more patients in the RTX group were in remission (40 vs. 25%). Duration of freedom from steroid use was longer in the RTX group, while body mass index was higher in the CNI arm (p > 0.05). No significant adverse events occurred in either group., Conclusion: The expenditure for the RTX and CNI groups was comparable, but there were fewer clinical encounters in the former group, potentially reducing the burden of healthcare on the patient's family.

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 <19 years from May 1, 2008 to May 1, 2013 at 12 pediatric dialysis units. Hepatitis B surface antibody (HBsAb) titers ≥10 mIU/ml were defined as protective., 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., (Copyright © 2017 by the American Society of Nephrology.)

Background: End-stage renal disease (ESRD) is associated with uremia and increased systemic inflammation. Alteration of the intestinal microbiota may facilitate translocation of endotoxins into the systemic circulation leading to inflammation. We hypothesized that children with ESRD have an altered intestinal microbiota and increased serum levels of bacterially derived uremic toxins., Methods: Four groups of subjects were recruited: peritoneal dialysis (PD), hemodialysis (HD), post-kidney transplant and healthy controls. Stool bacterial composition was assessed by pyrosequencing analysis of 16S rRNA genes. Serum levels of C-reactive protein (CRP), D-lactate, p-cresyl sulfate and indoxyl sulfate were measured., Results: Compared to controls, the relative abundance of Firmicutes (P = 0.0228) and Actinobacteria (P = 0.0040) was decreased in PD patients. The relative abundance of Bacteroidetes was increased in HD patients (P = 0.0462). Compared to HD patients the relative abundance of Proteobacteria (P = 0.0233) was increased in PD patients. At the family level, Enterobacteriaceae was significantly increased in PD patients (P = 0.0020) compared to controls; whereas, Bifidobacteria showed a significant decrease in PD and transplant patients (P = 0.0020) compared to control. Alpha diversity was decreased in PD patients and kidney transplant using both phylogenetic and non-phylogenetic diversity measures (P = 0.0031 and 0.0003, respectively), while beta diversity showed significant separation (R statistic = 0.2656, P = 0.010) between PD patients and controls. ESRD patients had increased serum levels of p-cresyl sulfate and indoxyl sulfate (P < 0.0001 and P < 0.0001, respectively). The data suggests that no significant correlation exists between the alpha diversity of the intestinal microbiota and CRP, D-lactate, or uremic toxins. Oral iron supplementation results in expansion of the phylum Proteobacteria., Conclusions: Children with ESRD have altered intestinal microbiota and increased bacterially derived serum uremic toxins.

Background and Objectives: Children with nephrotic syndrome can develop life-threatening complications, including infection and thrombosis. While AKI is associated with adverse outcomes in hospitalized children, little is known about the epidemiology of AKI in children with nephrotic syndrome. The main objectives of this study were to determine the incidence, epidemiology, and hospital outcomes associated with AKI in a modern cohort of children hospitalized with nephrotic syndrome., Design, Setting, Participants, & Measurements: Records of children with nephrotic syndrome admitted to 17 pediatric nephrology centers across North America from 2010 to 2012 were reviewed. AKI was classified using the pediatric RIFLE definition., Results: AKI occurred in 58.6% of 336 children and 50.9% of 615 hospitalizations (27.3% in stage R, 17.2% in stage I, and 6.3% in stage F). After adjustment for race, sex, age at admission, and clinical diagnosis, infection (odds ratio, 2.24; 95% confidence interval, 1.37 to 3.65; P=0.001), nephrotoxic medication exposure (odds ratio, 1.35; 95% confidence interval, 1.11 to 1.64; P=0.002), days of nephrotoxic medication exposure (odds ratio, 1.10; 95% confidence interval, 1.05 to 1.15; P<0.001), and intensity of medication exposure (odds ratio, 1.34; 95% confidence interval, 1.09 to 1.65; P=0.01) remained significantly associated with AKI in children with nephrotic syndrome. Nephrotoxic medication exposure was common in this population, and each additional nephrotoxic medication received during a hospitalization was associated with 38% higher risk of AKI. AKI was associated with longer hospital stay after adjustment for race, sex, age at admission, clinical diagnosis, and infection (difference, 0.45 [log]days; 95% confidence interval, 0.36 to 0.53 [log]days; P<0.001)., Conclusions: AKI is common in children hospitalized with nephrotic syndrome and should be deemed the third major complication of nephrotic syndrome in children in addition to infection and venous thromboembolism. Risk factors for AKI include steroid-resistant nephrotic syndrome, infection, and nephrotoxic medication exposure. Children with AKI have longer hospital lengths of stay and increased need for intensive care unit admission., (Copyright © 2015 by the American Society of Nephrology.)

Background: Focal segmental glomerulosclerosis (FSGS) is the most common glomerular condition leading to end-stage renal disease (ESRD) and the third most common cause of ESRD in pediatric patients., Methods: This is a retrospective study consisting of 22 pediatric patients with FSGS and heavy proteinuria. After demonstrating steroids resistance, the patients were treated with tacrolimus, targeting a trough level 5-8 ng/mL. The primary outcome is the induction of remission with tacrolimus., Results: Thirteen patients (59%) achieved remission (complete in 31.8% and partial in 27.2%) and 12 patients showed stable or improved renal function over an average follow-up of 2.9 years (range: 0.5-7 years). There was no significant difference in response rate between African American and Caucasian patients. None of the patients had significant side-effect to tacrolimus and none of the repeat biopsies showed an increase in interstitial fibrosis compared to baseline. The best renal outcome was for patients who achieved complete remission. Partially responsive patients had improved renal function compared with resistant patients., Conclusion: Tacrolimus is a viable option in the treatment of children with idiopathic steroid resistant FSGS.

FSGS recurs in approximately 30% of transplanted kidneys and may lead to graft loss. We retrospectively examined the efficacy of early and intensive PP without additional IS in pediatric kidney transplant patients with recurrent FSGS at our center. Seven of 24 patients (29%) had nephrotic proteinuria and histologic evidence of FSGS recurrence within 1-5 days post-transplantation. PP was initiated early after transplantation and initially performed daily until sustained decline in proteinuria. PP frequency was then individually tapered according to proteinuria. Recurrent FSGS in all seven patients responded to a four- to 32-wk course of PP. Two of seven patients had a second recurrence of FSGS, and both recurrences remitted after an additional 3-6 wk of PP. Median observation period was 4.5 yr (0.8-16.3 yr). Complete remission of recurrent FSGS has been sustained in all seven patients, and all patients have stable graft function with recent plasma creatinine <1.5 mg/dL in six of seven patients. Most recent urine protein/creatinine is 0.13-0.61 mg/mg in six of seven patients. One patient has heavy proteinuria secondary to chronic allograft nephropathy 16 yr post-transplant. Intensive and prolonged PP, when initiated early in the post-operative period, is effective in treating recurrent FSGS and preventing graft loss without the use of additional immunosuppressants., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)