Associations among erythropoietic, iron-related, and FGF23 parameters in pediatric kidney transplant recipients.

BACKGROUND: In pediatric kidney transplant recipients, anemia is common and oftentimes multifactorial. Hemoglobin concentrations may be affected by traditional factors, such as kidney function and iron status, as well as novel parameters, such as fibroblast growth factor 23 (FGF23). METHODS: Here, we evaluated associations among erythropoietic, iron-related, and FGF23 parameters in a cohort of pediatric kidney transplant recipients, hypothesizing that multiple factors are associated with hemoglobin concentrations. RESULTS: In a cross-sectional analysis of 59 pediatric kidney transplant recipients (median (interquartile range) age 16.3 (13.5, 18.6) years, median estimated glomerular filtration rate (eGFR) 67 (54, 87) ml/min/1.73 m2), the median age-related hemoglobin standard deviation score (SDS) was -2.1 (-3.3, -1.1). Hemoglobin SDS was positively associated with eGFR and calcium, and was inversely associated with erythropoietin (EPO), mycophenolate dose, and total, but not intact, FGF23. In multivariable analysis, total FGF23 remained inversely associated with hemoglobin SDS, independent of eGFR, iron parameters, EPO, and inflammatory markers, suggesting a novel FGF23-hemoglobin association in pediatric kidney transplant patients. In a subset of patients with repeat measurements, only delta hepcidin was inversely associated with delta hemoglobin SDS. Also, delta EPO positively correlated with delta erythroferrone (ERFE), and delta ERFE inversely correlated with delta hepcidin, suggesting a possible physiologic role for the EPO-ERFE-hepcidin axis in the setting of chronic kidney disease (CKD). CONCLUSION: Our study provides further insight into factors potentially associated with erythropoiesis in pediatric kidney transplant recipients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Electrocardiogram Standards for Children and Young Adults Using Z-Scores.

BACKGROUND: Normative ECG values for children are based on relatively few subjects and are not standardized, resulting in interpersonal variability of interpretation. Recent advances in digital technology allow a more quantitative, reproducible assessment of ECG variables. Our objective was to create the foundation of normative ECG standards in the young utilizing Z-scores. METHODS: One hundred two ECG variables were collected from a retrospective cohort of 27 085 study subjects with no known heart condition, ages 0 to 39 years. The cohort was divided into 16 age groups by sex. Median, interquartile range, and range were calculated for each variable adjusted to body surface area. RESULTS: Normative standards were developed for all 102 ECG variables including heart rate; P, R, and T axis; R-T axis deviation; PR interval, QRS duration, QT, and QTc interval; P, Q, R, S, and T amplitudes in 12 leads; as well as QRS and T wave integrals. Incremental Z-score values between -2.5 and 2.5 were calculated to establish upper and lower limits of normal. Historical ECG interpretative concepts were reassessed and new concepts observed. CONCLUSIONS: Electronically acquired ECG values based on the largest pediatric and young adult cohort ever compiled provide the first detailed, standardized, quantitative foundation of traditional and novel ECG variables. Expression of ECG variables by Z-scores lends an objective and reproducible evaluation without interpreter bias that can lead to more confident establishment of ECG-disease correlations and improved automated ECG readings in high-volume cardiac screening efforts in the young. Graphic Abstract: A graphic abstract is available for this article.

Incidence of Acute Post-Streptococcal Glomerulonephritis in Hawai'i and Factors Affecting Length of Hospitalization.

Acute post-streptococcal glomerulonephritis (APSGN) is a disorder of inflammation in the glomeruli and vasculature of the kidneys that is caused by immune-complex formation after Streptococcus pyogenes infection. Most patients with APSGN present with macroscopic hematuria, edema, and hypertension, however presentation can vary from no symptoms to severe proteinuria, or even acute renal failure. This study sought to estimate the incidence of APSGN among children in Hawai'i, to identify populations at increased risk for APSGN, and to recognize risk factors correlated with the length of hospitalization by subtype of APSGN (eg, pyoderma-associated, pharyngitis-associated). This retrospective review of 106 patients found that the incidence of APSGN in Hawai'i is greater than 4 per 100,000 children, which is significantly higher than the incidence of APSGN in high-income countries at 0.3 per 100,000 children. This increased incidence may be due to Hawai'i's unique racial group composition and therefore the unique immunologic response of the children of Hawai'i (particularly Pacific Islanders, who represent 62% of patients with APSGN in this study, but only represent 10% of Hawai'i's general population). In addition, there may be increased prevalence of nephritogenic strains of Streptococcus pyogenes in Hawai'i. The length of hospitalization was significantly increased in children with elevated serum creatinine levels (P <.0001) and lower bicarbonate levels (P =.0003).

Study design and rationale to assess Doxycycline Efficacy in preventing coronary Artery Lesions in children with Kawasaki disease (DEAL trial) - A phase II clinical trial.

BACKGROUND: Kawasaki disease (KD) is the most common acquired heart disease in children of the developed world, and triggers progressive coronary artery lesions (CAL) in 30% of cases if left untreated. Despite standard anti-inflammatory treatment for KD, CAL (dilation or aneurysm) still occurs in 5-10% of children, increasing their risk for fatal coronary artery complications. CAL is mediated by enhanced matrix metalloproteinase activity and elastin breakdown induced by the inflammatory process in the coronary artery wall. Doxycycline is an effective inhibitor of matrix metalloproteinases, and has been shown to reduce elastin breakdown and CAL in a mouse model of KD, but has not been evaluated in patients. OBJECTIVE: We aim to evaluate the efficacy of doxycycline in the prevention of CAL in children during the acute phase of KD. DESIGN: This is a phase II prospective, randomized, double-blinded, clinical trial in two steps. In Step 1, any child older than 1month with the diagnosis of KD will be included. Children with KD will be included in Step 2 if they develop coronary artery dilation (z-score≥2.5) within 20days from the onset of fever. Study subjects in Step 2 will be randomized to receive a 3-week course of doxycycline or placebo. EVALUATION: The efficacy of a 3-week doxycycline course during the acute phase of KD will be evaluated by measuring the decline in coronary artery z-scores from baseline with doxycycline treatment compared to placebo. CLINICAL TRIAL REGISTRATION: This study was registered on clinicaltrials.gov (NCT01917721).