Glomerular and tubular C4d depositions in IgA nephropathy: relations with histopathology and with albuminuria

Abstract

Background: C4d has been used as an evaluation marker for antibody-mediated rejection for solid organ transplantation. Although some studies have proposed that complement activation is involved in renal diseases, very little information is available on pathogenesis. This study was conducted to investigate C4d deposition in IgA nephropathy and to find its relations with histopathology and albuminuria.

Methods: This retrospective study included 23 patients who underwent renal biopsy at our medical center. The WHO grade of IgA nephropathy, interstitial inflammation and fibrosis, C4d staining and medical records including sex, age, and urine albumin were reviewed.

Results: Thirteen patients (56.5%) were positive for C4d staining in the glomerulus and eleven patients (47.8%) were positive in the tubular epithelium. Glomerular C4d deposition was associated with albuminuria (p=0.044), and tubular C4d deposition was associated with a higher grade of IgA nephropathy (p=0.014).

Conclusions: Activation of the complement system was involved in renal damage and was identified through deposition of C4d in the glomerulus and tubules. Positive C4d staining in the glomerulus and the tubules may be associated with functional damage related to glomerular filtration and poor renal outcome.

Keywords: Albuminuria; C4d; IgA; grade; nephropathy.

Figure 1

Hematoxylin and eosin (A and B), immunohistochemistry, immunofluorescence with IgA antibodies, and electron microscopic studies in IgA nephropathy and minimal change disease patient. The same granular pattern of IgA and C4d deposits are observed by immunohistochemical stain (C) and immunofluorescence (E). Electron-density deposits in the subendothelium were detected by electron microscopy (G). C4d depositions were not observed in minimal change disease (D, F and H).

Figure 2

Immunohistochemical C4d staining in IgA nephropathy patient. A. Glomerular C4d staining was distributed along the capillary loops in the glomerulus. The mesangial staining was suggested in small focus. B. Granular distribution of C4d staining was observed in tubular epithelium. A, B. Original magnification X400.

Figure 3

The number and percentage of IgA nephropathy patients with albuminuria and the grade of WHO classification. A. The degree of albuminuria was divided into group A (0, 1+: albuminuria < 30 mg/dL) and group B (2+, 3+: albuminuria > 30 mg/dL). There was statistical significance between group A and B, according to positivity of the glomerular C4d staining (p=0.044). B. The grade of WHO classification was sub-grouped into low grade (class I and II) and high grade (class III and IV). There was significant difference between two groups, according to C4d staining in tubular epithelium (p=0.014).