# Cryoglobulinaemia and Hepatitis C Glomerulonephritis

> Cryoglobulinaemia and hepatitis C glomerulonephritis for NEET-PG Medicine: Meltzer triad, mixed cryoglobulins, MPGN pattern, low C4 and antiviral therapy.

- Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/cryoglobulinaemia-and-hepatitis-c-glomerulonephritis
- Exam / course: NEET-PG · Subject: Medicine
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-14
- Last updated: 2026-10-14
- Reference basis: Harrison's Principles of Internal Medicine; Heptinstall's Pathology of the Kidney; Brenner and Rector's The Kidney
- How to cite: "Cryoglobulinaemia and Hepatitis C Glomerulonephritis", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/cryoglobulinaemia-and-hepatitis-c-glomerulonephritis

## Direct answer

Cryoglobulinaemia is the presence of immunoglobulins that precipitate at low temperature, and mixed cryoglobulinaemia most often arises from hepatitis C infection. It causes a membranoproliferative glomerulonephritis with low complement, typically a low C4, together with palpable purpura. Treatment targets the trigger, so direct-acting antivirals clear hepatitis C, while rituximab or plasma exchange is reserved for severe disease.

## What you must remember

- **Type I cryoglobulins:** monoclonal immunoglobulin, linked with lymphoproliferative disorders such as myeloma and Waldenström macroglobulinaemia.
- **Mixed cryoglobulins:** types II and III, with polyclonal or monoclonal IgM plus IgG, most often caused by hepatitis C.
- **Meltzer triad:** purpura, arthralgia or arthritis, and weakness, which together suggest mixed cryoglobulinaemia.
- **Renal pattern:** membranoproliferative glomerulonephritis with subendothelial deposits and intracapillary hyaline thrombi.
- **Complement:** low C4 is typical, and C3 may also be low, which helps distinguish the disease from other immune complex states.
- **Hepatitis C:** anti-HCV antibody and HCV RNA are tested in every patient with mixed cryoglobulinaemia.
- **Specimen handling:** blood is collected and transported at 37 °C, because cold exposure gives false-negative results.
- **Other features:** Raynaud phenomenon, livedo reticularis, peripheral neuropathy and cutaneous ulceration can accompany the disease.

## A diagnostic pathway for cryoglobulin-related kidney disease

Cryoglobulinaemic glomerulonephritis is easy to miss when the purpura is subtle, so the pathway starts from the clinical triad and the complement pattern. Each step narrows the cause and points to the right treatment, which is usually antiviral rather than immunosuppressive.

1. **Suspect the triad:** Palpable purpura on the legs, arthralgia and weakness with proteinuria or renal impairment suggest mixed cryoglobulinaemia.
2. **Send the sample warm:** Blood for cryoglobulins is collected and transported at 37 °C, because cooling causes the cryoprecipitate to fall out of solution.
3. **Screen for hepatitis C:** Anti-HCV antibody and HCV RNA are checked, since hepatitis C is the commonest cause of mixed cryoglobulinaemia.
4. **Check the complement:** A low C4 is typical, and its level, with a low C3 in some patients, helps place the picture within immune complex disease.
5. **Biopsy the kidney:** A membranoproliferative pattern with subendothelial deposits and intracapillary hyaline thrombi confirms cryoglobulinaemic glomerulonephritis.
6. **Treat the trigger first:** Direct-acting antivirals clear hepatitis C, and rituximab or plasma exchange is added for severe or non-hepatitis cases under specialist care.

Early antiviral treatment can improve both the skin disease and the kidney lesion, while delay risks progressive scarring. The biopsy is important because the same pattern can arise from other immune complex diseases.

## Where the examiner tries to catch you

Cryoglobulinaemia questions often test the pre-analytical trap and the link to hepatitis C.

- **Trap:** sending a cryoglobulin sample in a cold tube. — **Correct:** cryoglobulins precipitate in the cold and are lost, so the sample must be kept warm at 37 °C.
- **Trap:** attributing purpura with glomerulonephritis to IgA vasculitis by default. — **Correct:** IgA vasculitis shows IgA-dominant deposits with normal complement, whereas cryoglobulinaemia shows low C4 and hepatitis C infection.
- **Trap:** treating hepatitis C cryoglobulinaemia with steroids alone. — **Correct:** direct-acting antiviral therapy is the core treatment, and steroids or immunosuppression are reserved for severe disease under specialist guidance.

## Frequently asked questions

### What is the commonest cause of mixed cryoglobulinaemia?

Hepatitis C virus infection is the commonest cause of mixed cryoglobulinaemia, which is usually of type II. Screening for anti-HCV antibody and HCV RNA is therefore a key step in any patient with cryoglobulinaemic glomerulonephritis.

### What is the Meltzer triad in cryoglobulinaemia?

The Meltzer triad is purpura, arthralgia or arthritis, and weakness, which together suggest mixed cryoglobulinaemia. Renal involvement, peripheral neuropathy and Raynaud phenomenon can also occur in the same condition.

### Which kidney lesion is typical of hepatitis C cryoglobulinaemia?

Membranoproliferative glomerulonephritis with subendothelial deposits and intracapillary hyaline thrombi is the typical lesion of cryoglobulinaemic glomerulonephritis. The complement C4 level is often low, and it helps support the diagnosis.

### Why must blood for cryoglobulin testing be kept warm?

Cryoglobulins precipitate at low temperature, so a sample cooled in transit can lose its cryoprecipitate and give a false-negative result. Blood for cryoglobulin testing is therefore collected and transported at 37 °C.

### How is hepatitis C cryoglobulinaemic glomerulonephritis treated?

Direct-acting antiviral therapy clears hepatitis C and is the core treatment for cryoglobulinaemic glomerulonephritis. Rituximab or plasma exchange is reserved for severe kidney disease or for cases without hepatitis C, under specialist guidance.