The Canadian Childhood Nephrotic Syndrome (CHILDNEPH) project: Overview of design and methods

Background: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. Objectives: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. Design: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component). Setting: National study, comprised of all 13 Canadian pediatric nephrology clinics. Patients: 400 patients under 18 years of age to be recruited over 2.5 years. Measurements: Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups. Methods: All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care. Limitations: Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups. Conclusions: Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres

Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders

Objective. Vertebral fractures are an under-recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy. Methods. Children were categorized as follows: juvenile dermatomyositis (n = 30), juvenile idiopathic arthritis (n = 28), systemic lupus erythematosus and related conditions (n = 26), systemic arthritis (n = 22), systemic vasculitis (n = 16), and other conditions (n = 12). Thoracolumbar spine radiograph and dual x-ray absorptiometry for lumbar spine (L-spine) areal bone mineral density (BMD) were performed within 30 days of glucocorticoid initiation. Genant semiquantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative glucocorticoid dose, underlying diagnosis, L-spine BMD Z score, and back pain were analyzed for association with vertebral fracture. Results. Thirteen vertebral fractures were noted in 9 children (7%). Of these, 6 patients had a single vertebral fracture and 3 had 2-3 fractures. Fractures were clustered in the mid-thoracic region (69%). Three vertebral fractures (23%) were moderate (grade 2); the others were mild (grade 1). For the entire cohort, mean ± SD L-spine BMD Z score was significantly different from zero (-0.55 ± 1.2, P \u3c 0.001) despite a mean height Z score that was similar to the healthy average (0.02 ± 1.0, P = 0.825). Back pain was highly associated with increased odds for fracture (odds ratio 10.6 [95% confidence interval 2.1-53.8], P = 0.004). Conclusion. In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged glucocorticoid exposure. © 2010, American College of Rheumatology

Regression of target organ damage in children and adolescents with primary hypertension

We assessed the effects of 12 months of non-pharmacological and pharmacological therapy on 24-h ambulatory blood pressure, regression of target organ damage (TOD) and metabolic abnormalities in 86 children (14.1 ± 2.4 years) with primary hypertension. Twenty-four hour systolic and diastolic blood pressure (BP) decreased (130 ± 8 vs 126 ± 8, 73 ± 7 vs 70 ± 7, p = 0.0001 and 0.004 respectively). Body mass index (BMI) did not change, but waist-to-hip (0.85 ± 0.07 vs 0.83 ± 0.05, p = 0.01) and waist-to-height ratio (WHtR; 0.49 ± 0.07 vs 0.48 ± 0.05, p = 0.008) decreased. Left ventricular mass index (LVMi; 38.5 ± 10.7 vs 35.2 ± 7.5 g/m2.7, p = 0.0001), prevalence of left ventricular hypertrophy (46.5% vs 31.4%; p = 0.0001), carotid intima-media thickness (cIMT; 0.44 ± 0.05 vs 0.42 ± 0.04 mm, p = 0.0001), wall cross sectional area (WCSA; 7.5 ± 1.3 vs 6.9 ± 1.2 mm2, p = 0.002), hsCRP (1.1 ± 1.0 vs 0.7 ± 0.7 mg/l, p = 0.002), and LDL-cholesterol (115 ± 33 vs 107 ± 26 mg/dl, p = 0.001) decreased. Patients who had lowered BP had a lower cIMT at the second examination (0.41 ± 0.04 vs 0.43 ± 0.04 mm, p = 0.04) and lower initial hsCRP values (0.9 ± 0.7 vs 1.5 ± 1.3 mg/l, p = 0.04) in comparison to non-responders. Regression analysis revealed that the main predictor of LVMi decrease was a decrease in abdominal fat expressed as a decrease in waist circumference (WC) (R2 = 0.280, β = 0.558, p = 0.005), for WCSA-SDS a decrease in WC (R2 = 0.332, β = 0.611, p = 0.009) and for a cIMT-SDS decrease the main predictor was a decrease in hsCRP concentrations (R2 = 0.137, β = 0.412, p = 0.03). Standard antihypertensive treatment lowered BP and led to regression of TOD in hypertensive children. Lean body mass increase and decrease in abdominal obesity correlated with TOD regression

Unattended automated office blood pressure measurement in children

Purpose We studied the performance of unattended automated office blood pressure (uAOBP) measurement in children, in relation to oscillometric office BP (OBP) and ambulatory blood pressure monitoring (ABPM). Materials and Methods One hundred and eleven stable treated and untreated outpatients investigated for hypertension underwent uAOBP measurements (seated unattended in a quiet room separate from the renal clinic room, six times after a 5 min rest with the BpTRU device), and immediately before using the oscillometric device. Ambulatory 24 h blood pressure monitoring (ABPM) was performed on the same day in a subgroup of 42 children. Results UAOBP measurements were successful in 106 children (95%), 5 pre-school children did not tolerate to be alone in the room. The mean ± SD systolic/diastolic uAOBP, OBP and daytime ABP were 109.1 ± 14.0/70.8 ± 10.7 mmHg, 121.6 ± 16.5/77.6 ± 10.5 mmHg and 123.5 ± 11.3/73.7 ± 6.8 mmHg, respectively. Systolic/diastolic uAOBP was significantly lower than OBP by 13.6/7.6 mmHg (p < 0.0001) and lower than daytime ABP by 14.4 ± 0.5/2.9 ± 0.3 mmHg (p < 0.0001). The heart rate was not significantly different during uAOBP than during OBP measurements. On Bland Altman analysis the uAOBP underestimated OBP by a mean of 15.6 mmHg for systolic BP and by 8.6 mmHg for diastolic BP. In all 9 children with white-coat systolic hypertension uAOBP was within the normal range (<95th pc for OBP), in six of nine children with white-coat diastolic hypertension uAOBP was within the normal range however, in three of them it was elevated despite normal ABP. Conclusion uAOBP measurement is feasible in school-aged children, its values are considerably lower than OBP as well as daytime ABP and it could help with detection of white-coat systolic hypertension. The clinical applicability of uAOBP in children should be confirmed in further studies