Tests to diagnosis MPGN and cryoglobulinemia from hepatitis C
Other than a kidney biopsy, is there any other way to make the diagnosis of MPGN and cryoglobulinemia from hepatitis C?
Because the kidney disease cannot occur in the absence of active HCV viral replication, the first question to ask is as follows: “What is the status of the patient’s HCV?”
Many patients are being treated with the new direct acting antivirals (DAA) and have achieved viral remission.
If these patients are nephrotic or have impaired kidney function, then there will have to be an alternative explanation, because it is not likely a result of MPGN from HCV, and an alternative investigation is needed.
If the patient has active viral replication, then certain serologic testing may help confirm the diagnosis of HCV-related MPGN/cryoglobulinemia. When immune complexes, such as cryoglobulins, deposit and initiate an inflammatory response, they activate the complement cascade.
Cryoglobulins activate the classical complement pathway and lead to reduced serum concentrations of C3 and C4. It is improbable that a patient could have kidney disease because of type II cryoglobulins and not show complement activation. Ordering a C3 and C4 is essential in the work-up of these patients. Usually, both C3 and C4, but sometimes just the C4, is markedly depressed.
A serum cryoglobulins level can be checked, but the turnaround time for this assay is often not quick enough to help with the immediate diagnosis. More commonly, an indirect marker for the presence of cryoglobulins, called the rheumatoid factor, is measured. An IgM antibody directed against another IgG antibody is said to be anti-idiotypic, and if there are no other antigens involved, this is said to possess “rheumatoid factor” activity. In patients with rheumatoid arthritis, these immune complexes likely result in the pathogenesis of the disease. In other diseases that manifest antibodies that are anti-idiotypic, the test for the “rheumatoid factor” will be positive. A positive rheumatoid factor assay coupled with a low C3 and C4 is typical of active cryoglobulinemia.
