title: Mesangial C4d deposition may predict progression of kidney disease in pediatric patients with IgA nephropathy.
abstract: Data on the risk factors for chronic kidney disease in children with immunoglobulin A nephropathy (IgAN) are scarce. This study was aimed at investigating whether glomerular C4d immunostaining is a prognostic marker in pediatric IgAN.
  
  
  
  In this retrospective cohort study, 47 patients with IgAN biopsied from 1982 to 2010 were evaluated. Immunohistochemistry for C4d was performed in all cases. For analysis, patients were grouped according to positivity or not for C4d in the mesangial area. Primary outcome was a decline in baseline estimated glomerular filtration rate (eGFR) by 50% or more.
  
  
  
  Median follow-up was 8.3 years. Median renal survival was 13.7 years and the probability of a 50% decline in eGFR was 13% over 10 years. Nine children exhibited the primary outcome and 4 developed end-stage renal disease (ESRD). Compared with C4d-negative patients (n = 37), C4d-positive patients (n = 10) presented higher baseline proteinuria (1.66 ± 0.68 vs 0.47 ± 0.19 g/day/1.73 m2, p < 0.001), a progressive decline in eGFR (−10.04 ± 19.38 vs 1.70 ± 18.51 ml/min/1.73 m2/year; p = 0.045), and more frequently achieved the primary outcome (50.0 vs 10.8%, p = 0.013), and ESRD (30.0 vs 2.7%, p = 0.026). No difference was observed in Oxford classification variables. Baseline proteinuria, endocapillary hypercellularity and mesangial C4d deposition were associated with primary outcome in univariate analysis. Proteinuria and mesangial C4d deposition at baseline independently predicted the decline in eGFR. Renal survival was significantly reduced in C4d-positive patients (8.6 vs 15.1 years in C4d-negative patients, p < 0.001).
  
  
  
  In this exclusively pediatric cohort, positivity for C4d in the mesangial area was an independent predictor of renal function deterioration in IgAN.
authors.affiliation: Division of Clinical Nephrology, Clinics Hospital, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rafaela Cabral Gonçalves
authors.initials: RCG
authors.lastname: Fabiano
authors.affiliation: Division of Renal Pathology, Clinics Hospital, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Stanley
authors.initials: S
authors.lastname: de Almeida Araújo
authors.affiliation: Division of Renal Pathology, Clinics Hospital, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Eduardo Alves
authors.initials: EA
authors.lastname: Bambirra
authors.affiliation: Department of Pediatrics, Pediatric Nephrology Unit, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Eduardo Araújo
authors.initials: EA
authors.lastname: Oliveira
authors.affiliation: Department of Pediatrics, Pediatric Nephrology Unit, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Simões E Silva
authors.affiliation: Department of Pediatrics, Pediatric Nephrology Unit, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. svbpinheiro@gmail.com.|Universidade Federal de Minas Gerais-Faculdade de Medicina, Avenida Alfredo Balena 190/sala 331, Belo Horizonte, Minas Gerais, Brazil, 30130-100. svbpinheiro@gmail.com.
authors.forename: Sérgio Veloso Brant
authors.initials: SVB
authors.lastname: Pinheiro
mesh_terms: D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001706:Biopsy; D002648:Child; D015935:Complement C4b / Q000032:analysis* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology*; D005922:Glomerulonephritis, IGA / Q000473:pathology* / Q000652:urine; D006801:Humans; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000473:pathology* / Q000652:urine; D008297:Male; D010446:Peptide Fragments / Q000032:analysis* / Q000378:metabolism; D011379:Prognosis; D011507:Proteinuria / Q000652:urine; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: C4d staining; Children; Chronic kidney disease; Glomerulonephritis; IgA nephropathy; Proteinuria; Renal function