A comprehensive study of the association between hepatitis C virus and glomerulopathy.
BACKGROUND
Hepatitis C virus (HCV)-related infection is commonly associated with a wide range of glomerulonephritides (GN) including membranoproliferative glomerulonephritis (MPGN). The causal link between HCV infection and renal disease has been postulated through the induction of cryoglobulinaemia and secondary GN. However, the detection of viral particles or genomes within the kidneys of HCV-infected patients has proved to be difficult. With that in mind, we have studied a population of Egyptian HCV-positive patients with associated GN in an attempt to detect viral particles, antigens or RNA within their kidneys.


METHODS
Fifty patients were found to be HCV positive out of 303 who presented with a glomerulopathy between 1998 and 1999 at the Mansoura Urology and Nephrology Center, Egypt. Comprehensive investigations of these 50 patients were undertaken including an evaluation of their clinical, biochemical, histological, virological and immunological parameters. In addition, their kidney biopsy material was analysed by electron microscopy (EM) to detect viral particles, by immunohistochemistry to detect a viral core antigen and by RT-PCR to detect RNA. This was compared with 50 HCV-negative controls.


RESULTS
Positivity for HCV antibodies was higher among patients with GN (38%) compared with healthy blood donors (16%). Genotype 4 was sequenced in 70% of the HCV-positive samples examined. MPGN was the most common type of GN accounting for 54% of patients. Extrarenal manifestations were absent in the majority (80%) of patients even though 54% had cryoglobulinaemia. EM revealed virus-like particles in 50% of biopsies. Immunohistochemistry failed to reveal HCV-related antigens in kidney sections. HCV RNA was detected in the cryoprecipitates in 66% of patients and 22% of frozen renal sections. Control sections were negative.


CONCLUSIONS
Our findings suggest a causal link between HCV and GN based on the observation of virus-like particles as well as viral RNA within the kidney sections of patients with HCV-associated glomerulopathies.
Sabry
Alaa A
AA
Sheffield Kidney Institute, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK.
Sobh
Mohamed A
MA
Irving
William L
WL
Grabowska
Anna
A
Wagner
Bart E
BE
Fox
Samantha
S
Kudesia
Gura
G
El Nahas
A Meguid
AM
D000914:Antibodies, Viral / Q000032:analysis; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000648:ultrastructure / Q000821:virology; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D007678:Kidney Glomerulus / Q000821:virology*; D008297:Male; D008854:Microscopy, Electron; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014771:Virion / Q000648:ultrastructure
D000914:Antibodies, Viral; D012367:RNA, Viral