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NDT Advance Access originally published online on October 8, 2008
Nephrology Dialysis Transplantation 2009 24(3):886-891; doi:10.1093/ndt/gfn563
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org



Mesangial C4d deposition: a new prognostic factor in IgA nephropathy

Mario Espinosa1, Rosa Ortega2, Jose Manuel Gómez-Carrasco1, Fernando López-Rubio2, María López-Andreu1, María Ovidia López-Oliva1 and Pedro Aljama1

1 Servicio de Nefrologia 2 Servicio de Anatomía Patológica, Hospital Universitario Reina Sofia, Cordoba, Spain

Correspondence and offprint requests to: Mario Espinosa, Servicio de Nefrología, Hospital Universitario Reina Sofía, Avda Menéndez Pidal s/n, Cordoba 14004, Spain. Tel: +34-957-010440; Fax: +34-957-010307; E-mail: espinosahe{at}supercable.es



  Abstract

Background. It has been shown that patients with IgA nephropathy can be divided into two groups on the basis of the pattern of complement activation. Activation of the lectin pathway of complement is associated with more severe renal disease. Glomerular deposition of C4d is a marker of activation of the lectin pathway of complement. The aim of our study was to determine whether C4d staining at the time of the renal biopsy could identify patients with a different long-term prognosis in IgA nephropathy.

Methods. This retrospective cohort study included all patients with IgA nephropathy who underwent renal biopsy at our centre from January 1992 to December 2006. We evaluated baseline age, sex, presence of macroscopic haematuria, hypertension, serum creatinine and glomerular filtration rate (GFR), urine protein, mesangial C4d staining, glomerulosclerosis, interstitial fibrosis and extracapillary proliferation. Kaplan–Meier survival and Cox proportional hazards analyses were performed, with end-stage renal disease (ESRD) being defined as onset of dialysis or transplantation.

Results. Nineteen patients (32.2%) were C4d positive and 40 patients (67.8%) C4d negative. Age, hypertension, absence of macroscopic haematuria, serum creatinine levels, GFR, glomerular sclerosis, interstitial fibrosis and C4d-positive staining were all univariately associated with evolution to ESRD. Renal survival at 10 years was 43.9% in C4d-positive patients versus 90.9% in C4d-negative patients (log-rank, P = 0.0005).

Conclusion. Negative mesangial C4d staining in glomeruli in patients with IgA nephropathy helps to identify patients with a good long-term prognostic for whom aggressive treatments are not justified.

Keywords: C4d; complement; IgA nephropathy; lectin

Received for publication: 19. 2.08
Accepted in revised form: 16. 9.08


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