Prognostic value of glomerular C4d staining in patients with IgA nephritis

Mesangial IgA deposition is the initiative factor in the pathogenesis of IgA nephropathy (IgAN). Glomerular IgA depositon leads to activation local complement system. C4d positivity shows that complement activation occurs via alternative pathway. C4d positivity at the time of renal biopsy can be associated with poor prognosis in IgA nephropathy. We aimed to evaluate C4d deposition and renal outcome in patients with IgA nephritis.

Between January 2005 and December 2009, 40 patients with IgA nephritis were enrolled. Renal biopsy specimens of 33 patients have been evaluated. C4d immunohistochemical staining was performed 3-μm deparaffinized and rehydrated sections of formaldehyde-fixed renal tissues, using rabbit polyclonal anti-human C4d as the antibody. Baseline demographical, clinical and laboratory data were recorded retrospectively.

Mean age of the patients was 35.9 ± 12.9 years and female/male ratio was 19/21. Mean duration of follow-up was 32.8 (12-60) months. Baseline glomerular filtration ratio (GFR) and proteinuria were 55.8 ml/min and 2.44 gr/day respectively at the time of renal biopsy. Eleven patients were C4d positive. Presence of hypertension (p=0.133), proteinuria (p=0.007), serum creatinine levels (p=0.056) and glomerulosclerosis (p=0.004), mesengial hypersellularity (p=0.0001) and interstitial fibrosis (p=0.006) at the time of renal biopsy were higher in C4d positive group rather than negative group. Evolution to renal failure were 63.6% in C4d positive group and 13.6% in negative group (p=0.006). Renal survival at 3 years was 39% in C4d-positive patients versus 66.7% in the C4d-negative patients (log rank- p=0.0072).