The role of C4d immunostaining in the evaluation of the causes of renal allograft dysfunction.
BACKGROUND
Renal biopsy is the gold standard for diagnosis of acute rejection in renal transplant recipients. The Banff (1997) classification was revised in 2003 incorporating morphological criteria and C4d immunostaining for the diagnosis of acute antibody-mediated rejection.


OBJECTIVE
The aim of this study was to evaluate the role of histomorphology and C4d immunostaining in indicated renal allograft biopsies with a clinical follow-up for a minimum duration of 1 year.


METHODS
Histological analysis and C4d immunostaining were performed on 132 needle core biopsies and 2 nephrectomy specimens from 107 patients from July 2004 to June 2005.


RESULTS
Histological analysis revealed 59 cases of acute rejection, 10 biopsies of acute tubular necrosis, 41 cases of chronic allograft nephropathy (CAN), either alone or in combination with other diseases, and 18 biopsies of normal morphology. There were four cases of BK nephropathy (BK N) and eight cases had miscellaneous diagnoses. C4d immunostaining was performed on 126 biopsies. Overall, the prevalence of C4d positivity was 45% (57 of 126). Fifty-five percent (28 of 51) of the cases of acute rejection showed C4d positivity including 81% of presumptive antibody-mediated rejection (P-AbAR), 20% acute cellular rejection and 58% acute cellular rejection + P-AbAR. Overall C4d positivity was 37% in chronic allograft nephropathy. Acute tubular necrosis and borderline rejection showed 25 and 50% C4d positivity, respectively. Amongst various histological features, capillary margination of polymorphs and dilatation of peritubular capillaries (PTC-D) showed significant association with C4d positivity (P < 0.005). In cases of CAN, transplant glomerulopathy had significant association with C4d positivity. C4d-positive cases had a higher mean value of serum creatinine at the time of biopsies.


CONCLUSIONS
It is concluded that C4d staining is a useful adjunct marker of the humoral limb of rejection, both in early and late post-transplant periods.
Ranjan
Prabhat
P
Department of Histopathology, PGIMER, Chandigarh-160012, India.
Nada
Ritambhra
R
Jha
Vivekanand
V
Sakhuja
Vinay
V
Joshi
Kusum
K
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D002648:Child; D015935:Complement C4b / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D011446:Prospective Studies; D013997:Time Factors
D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d