Antibiotic treatment of children with E. coli O157:H7 infection increases the risk of the hemolytic-uremic syndrome.

The overall risk of hip fracture among Caucasian patients with ESRD is considerably higher than in the general population, independent of age and gender.

BackgroundSingle-center studies suggest that neonatal acute kidney injury (AKI) is associated with poor outcomes. However, inferences regarding the association between AKI, mortality, and hospital length of stay are limited due to the small sample size of those studies. In order to determine whether neonatal AKI is independently associated with increased mortality and longer hospital stay, we analyzed the Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) database.MethodsAll neonates admitted to 24 participating neonatal intensive care units from four countries (Australia, Canada, India, United States) between January 1 and March 31, 2014, were screened. Of 4273 neonates screened, 2022 (47·3%) met study criteria. Exclusion criteria included: no intravenous fluids ≥48 hours, admission ≥14 days of life, congenital heart disease requiring surgical repair at <7 days of life, lethal chromosomal anomaly, death within 48 hours, inability to determine AKI status or severe congenital kidney abnormalities. AKI was defined using a standardized definition —i.e., serum creatinine rise of ≥0.3 mg/dL (26.5 mcmol/L) or ≥50% from previous lowest value, and/or if urine output was <1 mL/kg/h on postnatal days 2 to 7.FindingsIncidence of AKI was 605/2022 (29·9%). Rates varied by gestational age groups (i.e., ≥22 to <29 weeks =47·9%; ≥29 to <36 weeks =18·3%; and ≥36 weeks =36·7%). Even after adjusting for multiple potential confounding factors, infants with AKI had higher mortality compared to those without AKI [(59/605 (9·7%) vs. 20/1417 (1·4%); p< 0.001; adjusted OR=4·6 (95% CI=2·5–8·3); p=<0·0001], and longer hospital stay [adjusted parameter estimate 8·8 days (95% CI=6·1–11·5); p<0·0001].InterpretationNeonatal AKI is a common and independent risk factor for mortality and longer hospital stay. These data suggest that neonates may be impacted by AKI in a manner similar to pediatric and adult patients.FundingUS National Institutes of Health, University of Alabama at Birmingham, Cincinnati Children’s, University of New Mexico.

An estimated 650,000 Americans will have ESRD by 2010. Young adults with kidney failure often develop progressive chronic kidney disease (CKD) in childhood and adolescence. The Chronic Kidney Disease in Children (CKiD) prospective cohort study of 540 children aged 1 to 16 yr and have estimated GFR between 30 and 75 ml/min per 1.73 m 2 was established to identify novel risk factors for CKD progression; the impact of kidney function decline on growth, cognition, and behavior; and the evolution of cardiovascular disease risk factors. Annually, a physical examination documenting height, weight, Tanner stage, and standardized BP is conducted, and cognitive function, quality of life, nutritional, and behavioral questionnaires are completed by the parent or the child. Samples of serum, plasma, urine, hair, and fingernail clippings are stored in biosamples and genetics repositories. GFR is measured annually for 2 yr, then every other year using iohexol, HPLC creatinine, and cystatin C. Using age, gender, and serial measurements of Tanner stage, height, and creatinine, compared with iohexol GFR, a formula to estimate GFR that will improve on traditional pediatric GFR estimating equations when applied longitudinally is expected to be developed. Every other year, echocardiography and ambulatory BP monitoring will assess risk for cardiovascular disease. The primary outcome is the rate of decline of GFR. The CKiD study will be the largest North American multicenter study of pediatric CKD.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (i.e. affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12, and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3, and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.

Background Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and factors associated with progression. Study Design Prospective assessment of risk factors for the composite event of renal replacement therapy (RRT) or 50% glomerular filtration rate (GFR) decline. Setting and Participants 496 children with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study. Outcomes Parametric failure time models were used to characterize adjusted associations between baseline levels and changes of predictors and the time to composite event. Results The cohort consisted of 398 children with non-glomerular and 98 children with glomerular disease, of whom 29% and 41%, respectively progressed to the composite event after a median follow-up of 5.2 and 3.7 years. Demographic, clinical characteristics and outcomes differed substantially according to underlying diagnosis, hence risk factors for progression were assessed in stratified analyses and formal interactions by diagnosis were performed. Among non-glomerular patients and after adjusting for baseline GFR, times to the composite event were significantly reduced with Up/c > 2 mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male gender and anemia by 79%, 69%, 38%, 40%, 38% and 45%, respectively. Among patients with glomerular disease, Up/c > 0.5 mg/mg, hypoalbuminemia and elevated blood pressure significantly reduced times to the composite event by 94%, 71% and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model which was cross validated internally. Limitations small number of events in glomerular patients and use of internal cross validation. Conclusions Characterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors, either alone or in combination, would shorten the time to RRT/50% decline of GFR in children with CKD.

Hemolytic uremic syndrome (HUS) usually occurs after infection with Shiga toxin-producing bacteria. Thrombotic thrombocytopenic purpura, a disorder with similar clinical manifestations, is associated with deficient activity of a circulating metalloprotease that cleaves von Willebrand factor at the Tyr842-Met843 peptide bond in a shear stress-dependent manner. We analyzed von Willebrand factor-cleaving metalloprotease activity and the status of von Willebrand factor in 16 children who developed HUS after Escherichia coli O157:H7 infection and in 29 infected children who did not develop this complication. Von Willebrand factor-cleaving metalloprotease activity was normal in all subjects, but von Willebrand factor size was decreased in the plasma of each of 16 patients with HUS. The decrease in circulating von Willebrand factor size correlated with the severity of thrombocytopenia and was proportional to an increase in von Willebrand factor proteolytic fragments in plasma. Immunohistochemical studies of the kidneys in four additional patients who died of HUS demonstrated glomerular thrombi in three patients, and arterial and arteriolar thrombi in one patient. The glomerular thrombi contained fibrin but little or no von Willebrand factor. A decrease in large von Willebrand factor multimers, presumably caused by enhanced proteolysis from abnormal shear stress in the microcirculation, is common in HUS. HUS, characterized by acute renal failure, hemolysis with schistocytes on blood smears, and thrombocytopenia, is accompanied by thrombotic microangiopathy of the kidneys and of other organs (1). The syndrome covers a diverse spectrum of microangiopathic disorders (2-4), but most cases occur after infection with Shiga toxin-producing bacteria, such as Escherichia coli O157:H7 (5) or Shigella dysenteriae serotype 1 (6).TTP, a disorder with some clinical, laboratory, and histopathologic similarities to HUS, has been associated with abnormal homeostasis of von Willebrand factor, a protein that is secreted from endothelial cells as a disulfide-linked polymer of a polypeptide with 2050 amino acid residues. Circulating von Willebrand factor is normally cleaved between Tyr842 and Met843 (7) in a shear stress-dependent manner (8) by a plasma metalloprotease (9, 10), generating a series of multimers. Without this metalloprotease activity, von Willebrand factor, when unfolded by shear stress (11), has increased platelet-aggregating activity (12). It is postulated that this increased activity facilitates the formation of arteriolar and capillary platelet thrombi in TTP. Indeed, acquired TTP has been associated with deficient von Willebrand factor-cleaving metalloprotease activity caused by inhibitory antibodies (12, 13).

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