From the Guidelines
Mixed cryoglobulinemia glomerulonephritis (GN) is primarily caused by hepatitis C virus (HCV) infection, which accounts for approximately 80-90% of cases, as well as autoimmune disorders and lymphoproliferative disorders, with the most recent evidence suggesting a significant association between HCV infection and type I membrano-proliferative glomerulonephritis 1. The causes of mixed cryoglobulinemia GN can be broken down into several categories, including:
- Hepatitis C virus (HCV) infection, which is the most common cause, accounting for approximately 80-90% of cases 1
- Autoimmune disorders, such as Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis
- Lymphoproliferative disorders, such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma
- Idiopathic cases, where no underlying cause can be identified The pathophysiology of mixed cryoglobulinemia GN involves the formation of immune complexes containing cryoglobulins, which deposit in small vessels, particularly in the kidneys, leading to inflammation and damage to the glomerular capillaries 1. The most effective treatment approach is to target the underlying cause, with direct-acting antivirals for HCV-related cases, immunosuppressants for autoimmune disorders, and appropriate therapy for lymphoproliferative conditions, with recent studies suggesting that antiviral therapy with direct-acting antivirals (DAAs) can lead to remission of mixed cryoglobulinemia GN in HCV-infected patients 1. Key points to consider in the treatment of mixed cryoglobulinemia GN include:
- Early evaluation of activity and severity of renal damage
- Individual tailoring of treatment
- Use of immunomodulating agents, such as glucocorticoids and immunosuppressants, in cases of cryoglobulinemic nephritis
- Use of antiviral therapy, particularly DAAs, in cases of HCV-related mixed cryoglobulinemia GN
- Consideration of poor prognostic variables, such as age, male gender, and poor blood pressure control, in determining treatment approach 1.
From the Research
Causes of Mixed Cryoglobulinemic Glomerulonephritis
The causes of mixed cryoglobulinemic glomerulonephritis (GN) can be attributed to various factors, including:
- Hepatitis C virus (HCV) infection, as mentioned in 2
- Hepatitis B virus (HBV) infection, as reported in 3
- Monoclonal gammopathy of undetermined significance, as seen in 4
- Other infectious or lymphoproliferative disorders, as stated in 2
- Connective tissue diseases, as mentioned in 2
- Immunologically mediated glomerular diseases, as reported in 2
Associated Conditions
Mixed cryoglobulinemic GN can be associated with:
- Purpura, weakness, and arthralgia, as mentioned in 2 and 5
- Nephrotic syndrome, as reported in 3
- End-stage renal disease, as seen in 6 and 3
- Vasculitis, as mentioned in 2 and 5
- Peripheral neuropathy, as reported in 3 and 5
Pathogenesis
The pathogenesis of mixed cryoglobulinemic GN involves the formation of cryoglobulins, which are proteins that precipitate from cooled serum, as explained in 2 and 5. These cryoglobulins can cause inflammation and damage to the glomeruli, leading to GN. The presence of HCV infection has been identified as a key factor in the pathogenesis of mixed cryoglobulinemic GN, as mentioned in 2 and 5.