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Hepatitis C virus-associated membranoproliferative glomerulonephritis in renal allografts
J M Cruzado1, S Gil-Vernet, G Ercilla
1Department of Nephrology, Ciutat Sanitària i Universitària de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Insights
Hepatitis C virus infection in kidney transplant recipients can cause type II cryoglobulinemia and membranoproliferative glomerulonephritis. Diagnostic tests are crucial for distinguishing this from transplant glomerulopathy.
Area of Science:
- Nephrology
- Virology
- Immunology
Background:
- Chronic allograft nephropathy is a major cause of kidney transplant failure.
- Transplant glomerulopathy is the glomerular manifestation of chronic allograft nephropathy.
- The association between hepatitis C virus (HCV) and glomerular damage in kidney allografts is not well understood.
Purpose of the Study:
- To investigate the potential link between HCV infection, cryoglobulinemia, and glomerular damage in renal allograft recipients.
- To determine if HCV can cause membranoproliferative glomerulonephritis (MPGN) in transplanted kidneys.
Main Methods:
- Studied six HCV-infected renal allograft recipients with proteinuria and microhematuria.
- Conducted virologic and immunologic assessments, including cryoprecipitate analysis.
- Performed renal histology and electron microscopy.
Main Results:
- All patients exhibited type II cryoglobulinemia (IgG polyclonal-IgM monoclonal).
- HCV RNA was significantly enriched in cryoprecipitate compared to serum.
- Renal histology showed prominent immunoglobulin M deposition and glomerular subendothelial electron-dense deposits.
Conclusions:
- HCV infection in kidney transplant recipients is associated with type II cryoglobulinemia and MPGN.
- Immunologic and virologic markers aid in differentiating HCV-associated MPGN from transplant glomerulopathy.
Abstract:
In renal transplantation, chronic allograft nephropathy is the leading cause of long-term graft losses, transplant glomerulopathy being its glomerular form. Differential diagnosis from recurrent or de novo membranoproliferative glomerulonephritis should be established. Whether hepatitis C virus is associated with cryoglobulinemia and glomerular damage in renal allograft recipients, as in native kidneys, is not known. We identified six hepatitis C virus-infected renal allograft recipients with proteinuria higher than 1.5 g/day, microhematuria, and membranoproliferative glomerulonephritis. Virologic and immunologic studies were conducted. Low serum levels of circulating immune complexes and cryoglobulins were observed, which were type II immunoglobulin G polyclonal-immunoglobulin Mk monoclonal in all six patients. Classical serum complement pathway activation and at least one type of autoantibodies were present in all of them. Hepatitis C virus RNA was found in higher concentrations in cryoprecipitate than in serum (percentage of enrichment ranged from 341 to 18,200%). Hepatitis C virus genotype was 1b in 4 of 6 patients, 1a in 1 of 6 patients, and 2a in 1 of 6 patients. In renal histology prominent parietal diffuse deposition of immunoglobulin M was the rule. Glomerular subendothelial electron-dense deposits with fibrillar appearance were observed in the two patients in which electron microscopy provided information about glomeruli. In renal allograft recipients hepatitis C virus infection may be associated with type II cryoglobulinemia which may lead to membranoproliferative glomerulonephritis. Immunologic and virologic studies may help to differentiate hepatitis C virus-associated membranoproliferative glomerulonephritis from transplant glomerulopathy.