Typical Hus: Evidence of Acute Phase Complement Activation from a Daycare Outbreak.

The clinical manifestations of typical hemolytic uremic syndrome (HUS) encompass a wide spectrum. Despite the potentially severe sequelae from this syndrome, treatment approaches remain supportive. We present the clinical course of a child who contracted Shiga toxin-positive E. coli (STEC) from a daycare center during an outbreak. Utilizing the modified Ham test which is a rapid, serum-based functional assay used to detect activation of the alternative pathway of complement as observed in atypical HUS, patient sera revealed evidence of increased complement activation in the acute phase of the syndrome but not after resolution. Further, this complement activation was attenuated by eculizumab in vitro, an effect that was replicated in vitro utilizing Shiga toxin as a stimulus of complement activation in normal serum. Our report suggests that complement blockade may be effective in the treatment of STEC-HUS when initiated early in the disease. Given the epidemic nature of the disease that limits the feasibility of randomized clinical trials, further studies are needed to determine the value of early eculizumab treatment in STEC-HUS.

Elevated uric acid and obesity-related cardiovascular disease risk factors among hypertensive youth.

BACKGROUND: Uric acid (UA) is associated with high blood pressure in adolescents and with left ventricular hypertrophy (LVH) and cardiovascular disease (CVD) in adults. We sought to determine if UA is independently associated with CVD risk factors and left ventricular mass (LVM) over time in hypertensive youth. METHODS: This was a 1-year prospective observational study of hypertensive children aged 3-19 years. Cross-sectional and longitudinal associations of serum UA with CVD risk factors and LVM were explored. RESULTS: Of the 49 children who completed both the baseline and 12-month assessments, at baseline the mean age was 13.8 years and mean UA was 5.5 mg/dL; 24% had elevated UA, 51% were overweight/obese and 39% had LVH. Measures of adiposity, low high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, LVM and LVH were all significantly associated with elevated UA at baseline, but not with change over time. Each 1 mg/dL increase in baseline UA was associated with a 2.5 g/m(2.7) increase in the LVM index at follow-up (95% confidence interval 0.64, 4.39; p = 0.01); after adjustment for age, sex, race, body mass index z-score, change in UA, time, blood pressure and medication use, this association was no longer significant. CONCLUSIONS: Hypertensive children with elevated UA have a higher prevalence of obesity-related CVD risk factors. Among hypertensive children, UA may be a marker of adiposity and not an independent CVD risk factor.

Kidney function and tobacco smoke exposure in US adolescents.

BACKGROUND AND OBJECTIVE: Active smoking and secondhand smoke (SHS) are known risk factors for kidney disease in adults. We evaluated the association between exposure to active smoking or SHS and kidney function in US adolescents. METHODS: This is a cross-sectional study in 7516 adolescents aged 12-17 who participated in NHANES 1999-2010 and had serum creatinine and cotinine measures. Active smoking was defined as self-reported smoking or serum cotinine concentrations >10 ng/mL. SHS was defined as nonactive smokers who self-reported living with ≥1 smokers or serum cotinine concentrations ≥ 0.05 ng/mL. Kidney function was determined by using the chronic kidney disease in children estimated glomerular filtration rate (eGFR) equation. RESULTS: Median (interquartile range) eGFR and serum cotinine concentrations were 96.8 (85.4-109.0) mL/minute per 1.73 m(2) and 0.07 (0.03-0.59) ng/mL, respectively. After multivariable adjustment, eGFR decreased 1.1 mL/minute per 1.73 m(2) (95% confidence interval [CI]: -1.8 to -0.3) per interquartile range increase in serum cotinine concentrations. The mean (95%CI) difference in eGFR for serum cotinine tertiles 1, 2, and 3 among children exposed to SHS compared to unexposed were -0.4 (-1.9 to 1.2), -0.9 (-2.7 to 0.9), and -2.2 (-4.0 to -0.4) mL/minute per 1.73 m(2), respectively (P = .03). The corresponding values among tertiles of active smokers compared to unexposed were 0.2 (-2.2 to 2.6), -1.9 (-3.8 to 0.0), and -2.6 (-4.6 to -0.6) mL/minute per 1.73 m(2) (P = .01). CONCLUSIONS: Tobacco smoke exposure was associated with decreased eGFR in US adolescents, supporting the possibility that tobacco smoke effects on kidney function begin in childhood.

Uric acid level and elevated blood pressure in US adolescents: National Health and Nutrition Examination Survey, 1999-2006.

Uric acid is associated with cardiovascular disease and cardiovascular disease risk factors in adults, including chronic kidney disease, coronary artery disease, stroke, diabetes mellitus, preeclampsia, and hypertension. We examined the association between uric acid and elevated blood pressure in a large, nationally representative cohort of US adolescents, a population with a relatively low prevalence of cardiovascular disease and cardiovascular disease risk factors. Among 6036 adolescents 12 to 17 years of age examined in the 1999-2006 National Health and Nutrition Examination Survey, the mean age was 14.5 years, 17% were obese (body mass index: ≥95th percentile), and 3.3% had elevated blood pressure. Mean serum uric acid level was 5.0 mg/dL, and 34% had a uric acid level ≥5.5 mg/dL. In analyses adjusted for age, sex, race/ethnicity, and body mass index percentile, the odds ratio of elevated blood pressure, defined as a systolic or diastolic blood pressure ≥95th percentile for age, sex, and height, for each 0.1-mg/dL increase in uric acid level was 1.38 (95% CI: 1.16-1.65). Compared with <5.5 mg/dL, participants with a uric acid level ≥5.5 mg/dL had a 2.03 times higher odds of having elevated blood pressure (95% CI: 1.38-3.00). In conclusion, increasing levels of serum uric acid are associated with elevated blood pressure in healthy US adolescents. Additional prospective studies and clinical trials are needed to determine whether uric acid is merely a marker in a complex metabolic pathway or causal of hypertension and, thus, a potential screening and therapeutic target.