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Background Children with chronic kidney disease (CKD) have delays in normal growth and pubertal development. We describe factors associated with delayed menarche and the association of delayed menarche with short stature in girls with CKD. Methods Two hundred eighty-seven girls with CKD onset prior to menarche within the Chronic Kidney Disease in Children (CKiD) cohort were studied. Delayed menarche was defined as menarche at age 15 years or older; short stature was defined as last available height 2 standard deviations below projected adult height. Kaplan-Meier cumulative incidence function was used to estimate median age at menarche. Chi-squared and Wilcoxon rank-sum tests were used to assess factors associated with delayed menarche. Chi-squared test was used to evaluate the association between delayed menarche and short stature. Results Among 287 girls, 68 enrolled with prevalent menarche, 131 were observed to have incident menarche, and 88 were pre-menarchal at their last study visit. Median age at menarche was 12 years. Ten percent had delayed menarche. African American race, lower estimated glomerular filtration rate, ever corticosteroid use, and longer CKD duration were associated with delayed menarche (p < 0.05). Girls with delayed menarche had lower height and weight percentiles at the time of menarche (p < 0.05). Sixty-one percent of girls with delayed menarche had short stature compared with only 35% of girls without delayed menarche (p = 0.03). Conclusion Median age at menarche is similar among girls with CKD and healthy girls. Ten percent of girls with CKD had delayed menarche and may be at risk for short stature., Author(s): Hannah S. Kim [sup.1] , Derek K. Ng [sup.2] , Matthew B. Matheson [sup.2] , Meredith A. Atkinson [sup.1] , Bradley A. Warady [sup.3] , Susan L. Furth [sup.4] [...]

Background Environmental lead exposure is associated with cognitive impairment in healthy children, with deficits seen in intelligence quotient (IQ), attention, and behavior. Neurocognitive dysfunction is also a well-described complication among children with chronic kidney disease (CKD). The objective was to evaluate the association between blood lead levels (BLL) and performance on neurocognitive assessments in a cohort of children with CKD. Methods Cross-sectional study of children with mild to moderate CKD from the Chronic Kidney Disease in Children (CKiD) multicenter prospective cohort study. The primary exposure was BLL. The primary outcome was performance on age-specific neurocognitive assessments evaluating IQ, executive functioning, attention, hyperactivity, and behavior. Multivariable linear regression was used to evaluate the association between BLL and neurocognitive performance, adjusted for key sociodemographic and clinical variables. Results A total of 412 subjects were included with median age 15.4 years, median estimated GFR 39 mL/min/1.73.sup.2, median BLL 1.2 mcg/dL, and median IQ score 99. In multivariable linear regression, higher BLL was associated with significantly lower IQ score (- 2.1 IQ points for every 1-mcg/dL increase in BLL, p = 0.029). Higher BLL was associated with worse scores on the Conners' Continuous Performance Test II Variability T-Score, a measure of inattention (+ 1.8 T-Score points for every 1-mcg/dL increase in BLL, p = 0.033). Conclusions Low-level lead exposure is associated with significantly lower IQ and more inattention in children with CKD, a population already at high risk for neurocognitive dysfunction. Universal screening for elevated BLL should be considered for all children with CKD at age 12-24 months., Author(s): Rebecca L. Ruebner [sup.1] , Stephen R. Hooper [sup.2] , Carisa Parrish [sup.1] [sup.3] , Susan L. Furth [sup.4] , Jeffrey J. Fadrowski [sup.1] Author Affiliations: (Aff1) grid.21107.35, 0000 [...]

Background Tyrosine kinase (TK) inhibitors are increasingly being used to treat a variety of pediatric malignancies. Reports in adult patients describe a range of effects of TK inhibitors on the kidney, including hypertension, proteinuria, acute kidney injury, and thrombotic microangiopathy (TMA); however, there are only a few reports of TK-inhibitor-associated nephrotic syndrome. Methods We report four pediatric patients with various malignancies (chronic myelogenous leukemia, acute lymphoblastic leukemia, and glioma/renal cell carcinoma) who developed nephrotic syndrome during treatment with TK inhibitors (imatinib, sunitinib, dasatinib, and quizartinib). One of the four patients also had clinical features of TMA. Results Three of the four patients achieved complete remission of nephrotic syndrome with discontinuation of the TK inhibitor and have had no additional nephrotic syndrome relapses to date. The temporal relationship of nephrotic syndrome onset to TK-inhibitor therapy and resolution of nephrotic syndrome with cessation of therapy strongly imply an association in these patients. Conclusions TK inhibitors are important therapies in pediatric cancer, and their use is expanding. Nephrotic syndrome with or without features of TMA is a potential complication of these therapies in children. Keywords Tyrosine kinase inhibitors * Nephrotic syndrome * Thrombotic microangiopathy * Acute kidney injury * Malignancy, Introduction Tyrosine kinase (TK) inhibitors have improved the prognosis of many pediatric cancers, especially chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). TK inhibitors are [...]

Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury (AKI). The outcomes of STEC HUS have improved, and the acute mortality rate in children is 1-4%. About 70 % of patients recover completely from the acute episode and the remainder have varying degrees of sequelae. Only a few retrospective studies have reviewed these patients over long periods. Methodological flaws include a lack of strict definitions, changing modes of treatment, ascertainment bias and loss of subjects to follow-up. The kidneys bear the brunt of the long-term damage: proteinuria (15-30 % of cases); hypertension (5-15 %); chronic kidney disease (CKD; 9-18 %); and end-stage kidney disease (ESKD; 3%). A smaller number have extra-renal sequelae: colonic strictures, cholelithiasis, diabetes mellitus or brain injury. Most renal sequelae are minor abnormalities, such as treatable hypertension and/or variable proteinuria. Most of the patients who progress to ESKD do not recover normal renal function after the acute episode. Length of anuria (more than 10 days) and prolonged dialysis are the most important risk factors for a poor acute and long-term renal outcome. After the acute episode all patients must be followed for at least 5 years, and severely affected patients should be followed indefinitely if there is proteinuria, hypertension or a reduced glomerular filtration rate (GFR). Keywords Hemolytic uremic syndrome * Long-term outcomes * Prognosis STEC HUS * D+HUS, Introduction The hemolytic uremic syndromes (HUS) are a major cause of acute kidney injury (AKI) in childhood and adults [1]. Before any causes were known, HUS was divided into diarrhea-associated [...]

OBJECTIVE. To determine the complications and risk factors for complications associated with using central venous catheters (CVCs) for the treatment of acute hematogenous osteomyelitis (AHO). METHODS. We conducted a retrospective cohort study of all patients admitted to the Children's Hospital of Philadelphia between January 1, 2000, and December 31, 2003, with a diagnosis of AHO. RESULTS. Eighty patients with AHO met inclusion criteria. The median age was 5 years, and 66% of the patients were male. The most commonly affected bones were the femur (25%), tibia (20%), and pelvis (16%). Staphylococcus aureus was the most common organism identified from cultures of bone (67%) and blood (30%). Seventy-five patients (94%) received >2 weeks of intravenous (IV) antibiotic therapy via a CVC and 5 (6%) received <2 weeks of IV antibiotic therapy before conversion to oral therapy for a median of 25 days. None of the patients who switched to oral therapy within 2 weeks was rehospitalized or returned to the emergency department. Of the 75 patients who received >2 weeks of IV therapy, 41% had [greater than or equal to] 1 CVC-associated complication. Seventeen patients (23 %) had a CVC malfunction or displacement, 8 (11%) had a catheter-associated bloodstream infection, 8 (11%) had fever with negative blood culture results, and 4 (5%) had a local skin infection at the site of catheter insertion. Older age was protective against the development of a CVC-associated complication, whereas the lowest median household income was associated with development of a CVC-associated complication. CONCLUSIONS. Interventions to reduce CVC-associated complications should be developed and evaluated, particularly for young children and those from families with low household incomes. Clinical trials are needed to evaluate the safety and efficacy of oral antibiotic therapy after a short course of IV therapy as an alternative to prolonged IV therapy. Key Words osteomyelitis, central venous catheters, treatment, antibiotic use, pediatric Abbreviations AHO--acute hematogenous osteomyelitis IV--intravenous CVC--central venous catheter IQR--interquartile range CHOP--Children's Hospital of Philadelphia ED--emergency department PICC--peripherally inserted central catheter OPAT--outpatient parenteral antibiotic Therapy, EACH YEAR IN the United States, 1 of 5000 children A common approach to the treatment of AHO has consisted of several days of antibiotic administration through peripheral intravenous (IV) […]

Background. Accepting kidneys for transplant from donors with a history of hepatitis B virus infection may increase the availability of organs for those with end-stage kidney disease. In adult recipients, kidney transplants from hepatitis B virus core antibody-positive donors have resulted in favorable graft and patient survival rates. However, pediatric organ transplant recipients have developing immune systems and a higher risk of infectious complications than adults. Accordingly, little is known about the outcomes of children who have received a kidney transplant from a hepatitis B virus core antibody-positive donor. Methods. We included 11 898 children ≤18 years of age who received a first kidney transplant in the United States between January 1, 1995, and December 31, 2010, and who were recorded in the Scientific Registry of Transplant Recipients. We examined differences in graft and patient survival rates among children who received a kidney transplant from a hepatitis B virus core antibody-positive donor. Results. There were 199 children (1.7%) who received a kidney transplant from a hepatitis B virus core antibody-positive donor. More than 80% of these transplants occurred in recipients who were hepatitis B virus core antibody and surface antigen negative. After a median follow-up of 7.9 years, there were no significant differences in the adjusted graft (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.80-1.31]) or patient (HR, 1.12 [95% CI, 0.73-1.73]) survival rates according to donor core antibody status. Conclusions. It may be acceptable, on a case-by-case basis, to consider hepatitis B virus core antibody-positive donors for kidney transplants to seroprotected children with end-stage kidney disease. [ABSTRACT FROM AUTHOR]

A 7-year-old male with poststreptococcal glomerulonephritis (PSGN) developed hemolytic uremic syndrome (HUS) and achieved remission. Hewas treated with eculizumab for 1 year. The eculizumab was discontinued and the patient remained in remission. This is the 10th reported case of PSGN associated with HUS. The histopathological feature observed at the 1-year follow-up was indistinguishable from the expected findings in an individual with healed PSGN without associated HUS. The relatively good prognosis in most prior cases and the absence of any reported recurrences strongly suggest that this form of atypical HUS does not warrant long-term eculizumab therapy. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease is strongly linked to neurocognitive deficits in adults and children, but the pathophysiologic processes leading to these deficits remain poorly understood. The NiCK study (Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease) seeks to address critical gaps in our understanding of the biological basis for neurologic abnormalities in chronic kidney disease. In this report, we describe the objectives, design, and methods of the NiCK study. Design/methods: The NiCK Study is a cross-sectional cohort study in which neurocognitive and neuroimaging phenotyping is performed in children and young adults, aged 8 to 25 years, with chronic kidney disease compared to healthy controls. Assessments include (1) comprehensive neurocognitive testing (using traditional and computerized methods); (2) detailed clinical phenotyping; and (3) multimodal magnetic resonance imaging (MRI) to assess brain structure (using T1-weighted MRI, T2-weighted MRI, and diffusion tensor imaging), functional connectivity (using functional MRI), and blood flow (using arterial spin labeled MRI). Primary analyses will examine group differences in neurocognitive testing and neuroimaging between subjects with chronic kidney disease and healthy controls. Mechanisms responsible for neurocognitive dysfunction resulting from kidney disease will be explored by examining associations between neurocognitive testing and regional changes in brain structure, functional connectivity, or blood flow. In addition, the neurologic impact of kidney disease comorbidities such as anemia and hypertension will be explored. We highlight aspects of our analytical approach that illustrate the challenges and opportunities posed by data of this scope. Discussion: The NiCK study provides a unique opportunity to address key questions about the biological basis of neurocognitive deficits in chronic kidney disease. Understanding these mechanisms could have great public health impact by guiding screening strategies, delivery of health information, and targeted treatment strategies for chronic kidney disease and its related comorbidities. [ABSTRACT FROM AUTHOR]

The article presents a case study of 12-year-old African American male with three months of abdominal pain, fatigue, nausea, emesis, and weight loss. On initial stage he features glomerulonephritis with severe acute kidney injury. On examination no glomeruli available for immunofluorescence. He received three days of pulse intravenous methylprednisolone followed by oral prednisone, intravenous cyclophosphamid. He was treated and never showed recurrence of gross hematuria and pulmonary symptoms.

Rationale & Objective: Infections cause significant morbidity and mortality for children receiving maintenance hemodialysis (HD). The Standardizing Care to Improve Outcomes in Pediatric End-Stage Kidney Disease (SCOPE) Collaborative is a quality-improvement initiative aimed at reducing dialysis-associated infections by implementing standardized care practices. This study describes patient-level risk factors for catheter-associated bloodstream infections (CA-BSIs) and examines the association between dialysis center-level compliance with standardized practices and risk of CA-BSI., Study Design: Prospective cohort study., Setting & Participants: Children enrolled in SCOPE between June 2013 and July 2019., Exposures: Data were collected on patient characteristics and center-level compliance with HD catheter care practices across the study period. Centers were categorized as consistent, dynamic (improved compliance over the study period), or inconsistent performers based on frequency of compliance audit submission and changes in compliance with HD care practices over time., Outcome: CA-BSIs., Analytical Approach: Generalized linear mixed models were used to evaluate (1) patient-level risk factors for CA-BSI and (2) associations between change in center-level compliance and CA-BSIs., Results: The cohort included 1,277 children from 35 pediatric dialysis centers; 1,018 (79.7%) had a catheter and 259 (20.3%) had an arteriovenous fistula or graft. Among children with a catheter, mupirocin use at the catheter exit site was associated with an increased rate of CA-BSIs (rate ratio [RR], 4.45; P = 0.004); the use of no antibiotic agent at the catheter exit site was a risk factor of borderline statistical significance (RR, 1.79; P = 0.05). Overall median compliance with HD catheter care practices was 87.5% (IQR, 77.3%-94.0%). Dynamic performing centers showed a significant decrease in CA-BSI rates over time (from 2.71 to 0.71 per 100 patient-months; RR, 0.98; P < 0.001), whereas no significant change in CA-BSI rates was detected among consistent or inconsistent performers., Limitations: Lack of data on adherence to HD care practices on the individual patient level., Conclusions: Improvement in compliance with standardized HD care practices over time may lead to a reduction in dialysis-associated infections., (Copyright © 2022 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Tubulointerstitial nephritis (TIN) is a cause of acute kidney injury in children characterized histologically by an inflammatory cell infiltrate in the kidney interstitium. The most common causes of TIN in children include medications, infections, inflammatory disorders, and genetic conditions. TIN typically presents with nonoliguric acute kidney injury and may be associated with systemic symptoms, including fever, rash, and eosinophilia. The long-term prognosis is generally favorable, with full kidney recovery; however, some patients may develop progressive chronic kidney disease. Immunosuppressive therapy may be indicated for severe or prolonged disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The Fontan operation is a palliative procedure for congenital single ventricle heart disease. Long-term kidney function in this cohort is not well-known. Our aim was to evaluate renal function in long-term survivors post-Fontan palliation, and we hypothesize that this cohort will have a higher prevalence of chronic kidney disease (CKD) compared to controls., Design: We performed a retrospective cohort study of 68 subjects evaluated through the Single Ventricle Survivorship Program at the Children's Hospital of Philadelphia between July 2010 and December 2014 compared to 70 healthy children similar in age and sex. Primary outcome was CKD, defined as estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m 2 using creatinine and cystatin C-based estimating equations. Secondary outcomes included proteinuria and elevated intact parathyroid hormone., Results: The Fontan cohort included 68 subjects with median age 13 years (IQR 9.0, 17.3) who were median 11.1 years (IQR 6.5, 15.7) post-Fontan palliation. This cohort was compared to 70 healthy individuals (median age 15.5 years (IQR 12.5, 18.3). Although median eGFRs were comparable: 102.6 vs. 101.9 mL/min/1.73 m 2 (P = .89) in Fontan vs. healthy subjects <18 years of age (Full CKiD equation), and 128.5 vs. 129.7 mL/min/1.73 m 2 (P = .56) in Fontan vs. healthy subjects ≥18 years of age (CKD-EPI creatinine and cystatin formula); 10% of Fontan subjects had an eGFR<90 mL/min/1.73 m 2 . Median intact parathyroid hormone level was higher at 59.4 pg/mL (IQR 43.0, 83.1) in the Fontan group compared to 23.4 pg/mL (IQR 16.7, 30.0) in controls (P ≤ .001). Proteinuria was present in 10% of the Fontan group compared to 4.7% in controls (P = .27)., Conclusion: Ten percent of long-term survivors post-Fontan palliation had eGFR <90 ml/min/1.73 m 2 , and higher median parathyroid hormone levels compared to controls. Taken together, these measures may indicate early kidney disease. Future studies will focus on longitudinal assessment of kidney function and evaluation of risk factors for CKD post-Fontan palliation., (© 2016 Wiley Periodicals, Inc.)

Background and Objectives: Prior studies suggested that women with CKD have higher risk for cardiovascular disease (CVD) and mortality than men, although putative mechanisms for this higher risk have not been identified. We assessed sex differences in (1) CVD risk factors and left ventricular hypertrophy (LVH), and (2) the relationship of left ventricular mass (LVM) with different measures of body size in children with CKD., Design, Setting, Participants, and Measurements: The study population comprised 681 children with CKD from the Chronic Kidney Disease in Children cohort, contributing 1330 visits. CVD risk factors were compared cross-sectionally by sex. LVH was defined as LVM/height 2.7 >95th percentile and LVM relative to estimated lean body mass (eLBM) >95th percentile for age and sex. Differences in LVM by sex were assessed by adjusting for age, weight, height, and eLBM using bivariate and multivariate regression models., Results: Girls were less likely to have uncontrolled hypertension (26% versus 38%, P=0.001), had lower diastolic BP z-scores (+0.3 versus +0.6, P=0.001), and had lower prevalence of high triglycerides (38% versus 47%, P=0.03) compared with boys. When LVH was defined by LVM indexed to height, girls had higher prevalence of LVH (16% versus 9%, P=0.01); when LVH was defined by LVM relative to eLBM, prevalence of LVH was similar between girls and boys (18% versus 17%, P=0.92). In regression models adjusting for eLBM, no sex differences in LVM were observed., Conclusions: Despite lack of increased prevalence of CVD risk factors, indexing LVM to height showed a higher proportion of LVH among girls, while estimates of LVH based on eLBM showed no sex differences. Indexing LVM to eLBM may be an alternative to height indexing in children with CKD., (Copyright © 2016 by the American Society of Nephrology.)

Tremendous advances have been made in understanding the pathogenesis of atypical Hemolytic Uremic Syndrome (aHUS), an extremely rare disease. Insights into the molecular biology of aHUS resulted in rapid advances in treatment with eculizumab (Soliris(®), Alexion Pharmaceuticals Inc.). Historically, aHUS was associated with very high rates of mortality and morbidity. Prior therapies included plasma therapy and/or liver transplantation. Although often life saving, these were imperfect and had many complications. We review the conditions included under the rubric of aHUS: S. pneumoniae HUS (SpHUS), inborn errors of metabolism, and disorders of complement regulation, emphasizing their differences and similarities. We focus on the clinical features, diagnosis, and pathogenesis, and treatment of aHUS that results from mutations in genes encoding alternative complement regulators, SpHUS and HUS associated with inborn errors of metabolism. Mutations in complement genes, or antibodies to their protein products, result in unregulated activity of the alternate complement pathway, endothelial injury, and thrombotic microangiopathy (TMA). Eculizumab is a humanized monoclonal antibody that inhibits the production of the terminal complement components C5a and the membrane attack complex (C5b-9) by binding to complement protein C5a. This blocks the proinflammatory and cytolytic effects of terminal complement activation. Eculizumab use has been reported in many case reports, and retrospective and prospective clinical trials in aHUS. There have been few serious side effects and no reports of tachphylaxis or drug resistance. The results are very encouraging and eculizumab is now recognized as the treatment of choice for aHUS.

Objectives: Adult solid organ transplant (SOT) recipients commonly develop advanced kidney disease; however, the burden of end-stage kidney disease (ESKD) in children after SOT is not well-described. The objectives of this study were to determine the incidence of ESKD after pediatric SOT and the relative risk by SOT type., Methods: Retrospective multicenter cohort study of children, ages ≤ 18 years, who received SOTs from 1990 through 2010 using Scientific Registry of Transplant Recipients data linked to the US Renal Data System. We performed a competing risks analysis to determine cumulative incidence of ESKD (chronic dialysis or kidney transplant), treating death as a competing risk, and fit a multivariable Cox regression model to assess hazard of ESKD by organ type., Results: The cohort included 16,604 pediatric SOT recipients (54% liver, 34% heart, 6% lung, 6% intestine, and 1% heart-lung). During a median follow-up of 6.2 years (interquartile range 2.2-12.1), 426 (3%) children developed ESKD. Compared with liver transplant recipients, in whom the incidence of ESKD was 2.1 cases per 1000 person-years, in adjusted analyses the highest risk of ESKD was among intestinal (hazard ratio [HR] 7.37, P < .001), followed by lung (HR 5.79, P < .001) and heart transplant recipients (HR 1.79, P < .001)., Conclusions: In a 20-year national cohort of pediatric SOT recipients, the risk of ESKD was highest among intestinal and lung transplant recipients. The burden of earlier stages of chronic kidney disease is probably much higher; modifiable risk factors should be targeted to prevent progressive kidney damage in this high-risk population.

Purpose of Review: Streptococcus pneumoniae associated hemolytic uremic syndrome (SpHUS) is defined by the occurrence of acute hemolytic anemia, thrombocytopenia and acute kidney injury in a patient with a S. pneumoniae infection. We review the pathophysiology, clinical course, treatment and prognosis for SpHUS. We also describe an expanded classification system that uses additional diagnostic criteria to identify more patients with a high likelihood of having SpHUS., Recent Findings: SpHUS often may be underdiagnosed because of overlapping features with disseminated intravascular coagulation (DIC) and the lack of strict diagnostic criteria. The epidemiology has changed with the emergence of different pneumococcal serotypes as newer pneumococcal vaccines have been introduced., Summary: SpHUS accounts for 5-15% of all HUS cases. The majority of SpHUS patients have pneumonia and a low mortality rate in contrast to those with meningitis, who have a more severe clinical course. Although the pathogenesis of SpHUS remains unknown, the Thomsen-Friedenreich antigen seems to play a central role. S. pneumoniae produces neuraminidase, thereby exposing the Thomsen-Friedenreich antigen on the surface of cell membranes. Thomsen-Friedenreich antigen exposure can result in hemolysis and direct endothelial injury leading to HUS phenotype. Early identification of these patients is critical so that fresh frozen plasma may be avoided.