Impact of in vivo complement activation and cryoglobulins on graft outcome of HCV-infected renal allograft recipients.
BACKGROUND
Chronic hepatitis C virus (HCV) infection is closely associated with mixed cryoglobulinemia. Cryoglobulins can activate complement leading to vascular damage. We examined whether cryoglobulinemia and complement turnover is associated with HCV infection in renal transplant recipients and whether this has an adverse effect on graft outcome.


METHODS
Sera and fresh plasma from 31 HCV-RNA-positive patients after renal transplantation (group I) were studied for cryoglobulins, complement hemolytic activity (CH50), and complement split product C3d. In total, 80 HCV-negative renal transplant recipients (group II) and 72 untreated patients with chronic hepatitis C (group III) without renal transplantation served as controls.


RESULTS
Cryoglobulins were detected in 45, 28, and 26% of the patients in group I, II, and III, respectively. A high cryocrit ( > 5%) was present only in patients of group III (p < 0.01%). Mean CH50 values were lower and C3d levels higher in HCV-positive patients (group I and III) compared with HCV-negative patients (p < 0.0001). Cryoglobulins were not associated with extrahepatic manifestations or graft dysfunction, except in five patients of group III demonstrating cryoglobulinemic vasculitis. HCV-positive renal transplant recipients with signs of complement activation showed a significantly greater increase of serum creatinine (0.88 +/- 1.14 mg/dL) when compared with baseline than patients without complement activation (0.34 +/- 0.37 mg/dL; p = 0.035). There was also a tendency toward a higher extent of proteinuria in patients with complement activation (1.38 +/- 2.17 g/d vs. 0.50 +/- 0.77 g/d; p = 0.25, NS).


CONCLUSIONS
Cryoglobulins are common in renal allograft recipients, but do not affect graft function. However, complement activation appears to be involved in chronic allograft dysfunction in HCV-infected recipients.
Weiner
Stefan M
SM
Department of Medicine, Marienhospital, Ruhr-University Bochum, Hoelkeskampring 40, Herne, Germany. Stefan.Weiner@ruhr-uni-bochum.de
Thiel
Jens
J
Berg
Thomas
T
Weber
Sabine
S
Krumme
Bernd
B
Peter
Hans H
HH
Rump
Lars C
LC
Grotz
Wolfgang H
WH
D000328:Adult; D016022:Case-Control Studies; D003167:Complement Activation; D015933:Complement C3d / Q000276:immunology; D015941:Complement Hemolytic Activity Assay; D003404:Creatinine / Q000097:blood; D003449:Cryoglobulinemia / Q000276:immunology*; D003450:Cryoglobulins / Q000276:immunology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D008297:Male; D008875:Middle Aged
D003450:Cryoglobulins; D015933:Complement C3d; D003404:Creatinine