Incidence of C4d staining in protocol biopsies of stable renal allografts: A multicenteR study

 

 

M. Mengel1, J. Bogers2, D. Serón3, W. Gwinner4 and H. Haller4 for the ESPRIT5 Group

 

1Institut fuer Pathologie, Medizinische Hochschule Hannover, Hannover, Germany

2Laboratorium anatomo – pathologie, Universitair Ziekenhuis Antwerpen, Antwerpen, Belgium

3Servicio de Nefrologia, Hospital Universitario de Bellvitge, Barcelona, Spain

4Abteilung Nephrologie, Medizinische Hochschule Hannover, Hannover, Germany

5European Study Group For Protocol Biopsies In Renal Transplantation

 

Background:

C4d staining in peritubular capillaries (PTC) of renal allografts has been established as an in situ marker of acute and chronic humoral rejection, which is frequently accompanied by circulating donor-specific-antibodies. To date, the incidence of C4d deposition in protocol biopsies from stable renal allografts in comparison to that of indication biopsies performed because of impaired graft function has not been reported yet. Furthermore, to test whether center specific factors are influencing the incidence of antibody mediated rejection we performed a multicenter study investigating specimens from the European Study Group for Protocol Biopsies In Renal Transplantation (ESPRIT).

 

Patients and Methods:

Protocol and indication renal allograft biopsies were contributed from the transplant centers in Hannover, Germany, Barcelona, Spain, and Antwerp, Belgium. Sections from 745 paraffin embedded biopsies were stained by immunohistochmemistry using a commercially available polyclonal antiserum. All stains were done centrally in one laboratory and evaluated by one of the authors to exclude any interlaboratory and interobserver variations. Every participant provided adequate controls. C4d results in PTC were recorded in five groups: >50% of PTC C4d positive, 25-50%, 5-25%, <5%, C4d negative.

 

Results:

TX-center

type of biopsy (Bx)

n Bx

C4d (%)

>50%PTC

C4d (%)

25-50%PTC

C4d (%)

5-25%PTC

C4d (%)

<5%PTC

C4d

negative

center 1

indication Bx

230

26 (11.3)

17 (7.4)

30 (13.0)

23 (10.0)

134 (58.3)

center 2

indication Bx

48

5 (10.4)

7 (14.6)

7 (14.6)

11 (22.9)

18 (37.5)

total indication BX

278

31 (11.2)

24 (8.6)

37 (13.3)

34 (12.2)

152 (54.7)

center 1

protocol Bx

329

4 (1.2)

7 (2.1)

22 (6.6)

21 (6.3)

275 (83.5)

center 2

protocol Bx

91

0

1 (1.1)

6 (6.6)

15 (16.5)

69 (75.8)

center 3

protocol Bx

47

3 (6.4)

1 (2.1)

0

4 (8.5)

39 (83.0)

total protocol Bx

467

7 (1.5)

9 (1.9)

28 (6.0)

40 (8.6)

383 (82.0)

total

745

38 (5.1)

33 (4.4)

65 (8.7)

74 (9.9)

535 (71.8)

 

 

 

Conclusions:

The incidence of positive C4d staining in protocol biopsies is lower than in indication biopsies. However, cases of "subclinical" diffuse Cd4 deposition in PTC of stable grafts occur. The significance of this finding remains to be determined. The causes underlying the differences between participating centers in the incidence of C4d detection need to be explored further.

 

 

 

 

 

 

 

Incidence of C4d staining in protocol biopsies of stable renal allografts: A multicenteR study

 

M. Mengel1, J. Bogers2, D. Serón3, W. Gwinner4 and H. Haller4 for the ESPRIT5 Group

 

 

1Institut fuer Pathologie, Medizinische Hochschule Hannover, Hannover, Germany

2Laboratorium anatomo – pathologie, Universitair Ziekenhuis Antwerpen, Antwerpen, Belgium

3Servicio de Nefrologia, Hospital Universitario de Bellvitge, Barcelona, Spain

4Abteilung Nephrologie, Medizinische Hochschule Hannover, Hannover, Germany

5European Study Group For Protocol Biopsies In Renal Transplantation

 

 

 

 

Corresponding author:

Dr. med. Michael Mengel

Institut fuer Pathologie

Medizinische Hochschule Hannover

Carl Neuberg Strasse 1

30625 Hannover – Germany

Tel. +49-511-532-4487

Fax +49-511-532-5799

Email: mengel.michael@mh-hannover.de