C4D: A DIAGNOSTIC MARKER FOR HUMORAL RENAL ALLOGRAFT REJECTION WITH GLOMERULITIS

 

Kiril Trpkov1, S. Yilmaz2, W. Truong1, H. Benediktsson1

1Department of Pathology and Laboratory Medicine and  2Department of Surgery,   

 University of Calgary, Calgary, Alberta, Canada

 

 

Introduction:

Acute humoral rejection (AHR) is a distinct type of alloantibody-mediated rejection and recent reports suggest high specificity and sensitivity for complement split product C4d deposition in peritubular capillaries (PTC) and glomeruli in AHR. We sought to determine C4d deposition in acute humoral and tubulointerstitial rejection, acute tubular necrosis, chronic allograft nephropathy, drug toxicity, and protocol and baseline biopsies.

 

Material and Methods:

We examined retrospectively by indirect immunofluorescence C4d expression in 116 renal biopsies from 89 allografts in which frozen tissue specimens were stored at the time of the biopsy and that were of adequate technical quality. Staining was evaluated in PTC, glomeruli, arteries, and arterioles as C4d negative (-), and focal or diffuse C4d positive (+).

 

Results and Discussion:

C4d(+) staining was observed in 11 biopsies from 8 allografts and all biopsies demonstrated acute rejection: 6 with glomerulitis, 4 with intimal arteritis, 8 with tubulitis and one with extensive ischemic necrosis. Nine of the C4d(+) biopsies (from 7 allografts) occurred within one month after transplantation. Only one patient had two C4d(+) biopsies within the second year after transplantation. All allografts originated from cadaveric donors. Demographics of the C4d(+) allograft recipients included four male and four female patients (five Caucasians, one each Oriental, Black, and Filipino). Two patients had previous allografts and three women had history of previous pregnancies. Antibody-mediated rejection was felt to occur in 7 biopsies (from 6 allografts) based on the pathology and the clinical findings and two of these allografts were lost. Both patients who lost their grafts were females (one with previous allograft and two pregnancies, one with four previous pregnancies). All remaining patients have functioning allografts. Focal C4d(+) staining was seen in only two protocol biopsies showing recurrent lupus nephritis and borderline rejection. C4d(-) staining was observed in all other protocol and baseline biopsies and biopsies exhibiting acute tubular necrosis, drug toxicity and chronic allograft nephropathy. In this selected study group C4d was seen only in one patient after the first year after transplantation.  C4d staining represents a sensitive and specific diagnostic tool for the early detection of AHR with glomerulitis.

 

 

 

 

C4D: A DIAGNOSTIC MARKER FOR HUMORAL RENAL ALLOGRAFT REJECTION WITH GLOMERULITIS

 

Kiril Trpkov, MD FRCPC

Assistant Professor, University of Calgary

Staff Pathologist, Anatomical Pathology, Rockyview Hospital

7007, 14 street, Calgary, AB, T2V 1P9

 

Phone: 943-3443

Fax:  943-3333

E-mail: kiril.trpkov@cls.ab.ca