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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]