Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

Background: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration >= 5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). Methodology/Principal Findings: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. Conclusions: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin

Decreased renal function in overweight and obese prepubertal children

BACKGROUND: Obesity is a potentially modifiable risk factor for the development and progression of kidney disease, both in adults and children. We aim to study the association of obesity and renal function in children, by comparing estimated glomerular filtration rate (eGFR) in nonoverweight and overweight/obese children. Secondarily, we aim to evaluate the accuracy of equations on eGFR estimation when compared to 24-h urinary creatinine clearance (CrCl). METHODS: Cross-sectional study of 313 children aged 8-9 y, followed in the birth cohort Generation XXI (Portugal). Creatinine and cystatin C, GFR estimated by several formulas and CrCl were compared in 163 nonoverweight and 150 overweight/obese, according to World Health Organization growth reference. RESULTS: Overweight/obese children had significantly lower eGFR, estimated by all methods, except for CrCl and revised Schwartz formula. Despite all children having renal function in the normal range, eGFR decreased significantly with BMI z-score (differences ranging from -4.3 to -1.1 ml/min/1.73 m(2) per standard deviation of BMI). The Zappitelli combined formula presented the closest performance to CrCl, with higher correlation coefficients and higher accuracy values. CONCLUSION: Young prepubertal children with overweight/obesity already present significantly lower GFR estimations that likely represent some degree of renal impairment associated with the complex deleterious effects of adiposity

Pw01-003 – Frequency Of Mefv Mutations In Turkish Population

PubMe

Childhood vasculitides in Turkey: A nationwide survey

PubMedID: 16586044Aim: The aims of this study were to evaluate the characteristics of childhood vasculitides and to establish the first registry in Turkey, an eastern Mediterranean country with a white population. Patients and methods: A questionnaire was distributed to the main referral centers asking for the registration of the Henoch-Schönlein purpura (HSP) patients in the last calendar year only and 5 years for other vasculitides. Demographic, clinical, and laboratory data were assessed. Results: Vasculitic diseases were registered from 15 pediatric centers. These centers had a fair representation throughout the country. In the last calendar year, incidences were as follows: HSP 81.6%, Kawasaki disease (KD) 9.0%, childhood polyarteritis nodosa (C-PAN) 5.6%, Takayasu arteritis (TA) 1.5%, Wegener's granulomatosis 0.4%, and Behçet disease 1.9%. There was no clear gender dominance. The mean age was 11.05±4.89 years. Acute phase reactants were elevated in almost all, highest figures being in C-PAN. Renal involvement was present in 28.6% of HSP and 53% of the C-PAN patients. Abdominal aorta was involved in all TA patients. Among the C-PAN patients, 25% had microscopic PAN with necrotizing glomerulonephritis; antineutrophil cytoplasmic antibody was positive in those who were studied. Among the patients, 12.5% and 15% had classic PAN and cutaneous PAN, respectively. The remaining majority were classified as systemic C-PAN diagnosed with biopsies and/or angiograms demonstrating small to midsize artery involvement. The overall prognosis was better than reported in adult series. Conclusion: This is the largest multicenter study defining the demographic data for childhood vasculitides. The distribution of childhood vasculitides was different in our population where KD is much less frequent, whereas HSP constitutes an overwhelming majority. C-PAN was more frequent as well. © Clinical Rheumatology 2006

Familial Mediterranean fever with a single MEFV mutation: comparison of rare and common mutations in a Turkish paediatric cohort

Objective. Presence of common MEFV gene mutations strengthened the diagnosis of FMF in addition to the typical clinical characteristics of FMF. However, there are also rare mutations. P369S, A744S, R761H, K695R, F479L are the main rare mutations in Turkish population. We aimed to evaluate FMF patients with a single allele MEFV mutation and to compare patients with common and rare mutations