Condition Deep-Dives 12 min read·Updated 22 July 2026 Clinician-reviewed

Cryoglobulinaemic Glomerulonephritis

A UK Consultant Nephrologist on cryoglobulinaemic GN — once a hepatitis C disease, now usually curable with direct-acting antivirals, but still a rituximab-and-plasma-exchange emergency when severe.

  • Clinically Reviewed
  • NHS & NICE Aligned
  • UK Evidence-Based
  • Last Reviewed 22 July 2026

Professor Mohammed Mahdi Althaf

Consultant Nephrologist & Acute Physician

View Credentials

Professor Mohammed Mahdi Althaf

MD, MSc, PgDip (Clin Ed), FRCP, FHEA, FASN

Consultant Nephrologist & Acute Physician · GMC 7216325

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Direct answer

MPGN with intracapillary pseudothrombi. Mixed (type II/III) drives most renal disease; HCV is the dominant cause. Treat the trigger: DAAs cure HCV-related disease in > 95%. Add rituximab ± PLEX for severe vasculitis.

Key recommendation: Type II mixed cryoglobulinaemia + HCV = classic.

Quick answer

✓ Best choices

  • Plant proteins: beans, lentils, tofu, tempeh, chickpeas
  • Vegetables, fruit and whole grains
  • Oily fish 1–2 times a week
  • Olive oil as the main cooking fat

✓ Foods to limit

  • Added salt (≤ 6 g/day)
  • Processed meats and high-additive ready meals
  • Excess animal protein at every meal

Key takeaway

MPGN with intracapillary pseudothrombi. Mixed (type II/III) drives most renal disease; HCV is the dominant cause. Treat the trigger: DAAs cure HCV-related disease in > 95%. Add rituximab ± PLEX for severe vasculitis.

Who should be cautious

People on dialysis, post-transplant, pregnant or breastfeeding, or taking prescription medication — confirm with your renal team before changes.

Cryoglobulinaemic Glomerulonephritis

Classification & causes

Brouet Classification

  • TYPE I (10–15%): single monoclonal Ig (usually IgM, IgG)

— Myeloma, Waldenström, MGUS, CLL — Hyperviscosity, acrocyanosis, digital ischaemia

  • TYPE II (50–60%): monoclonal IgM (RF activity) + polyclonal IgG

— HCV in 80% of UK cases — Lymphoma, Sjögren, autoimmune — Commonest cause of renal disease

  • TYPE III (25–30%): polyclonal IgM + polyclonal IgG

— Connective tissue disease, chronic infection — Milder renal disease

UK Epidemiology

  • HCV remains commonest trigger despite eradication programme
  • Sjögren-associated cryo rising as recognised cause
  • Always screen for HCV, HBV, HIV, MGUS at presentation

Clinical features & diagnosis

Presentation

  • Meltzer triad: palpable purpura + arthralgia + weakness
  • Lower-limb purpura (cold-dependent, 90%)
  • Peripheral neuropathy (sensorimotor)
  • Raynaud, cutaneous ulcers, livedo
  • Renal: proteinuria, haematuria, AKI, hypertension
  • Pulmonary haemorrhage, mesenteric vasculitis (rare, severe)

Investigations

  • Cryoglobulin (keep blood warm to lab, 37°C tube)
  • Cryocrit > 1% supports diagnosis
  • C4 very low, C3 normal or mildly low
  • RF positive (especially type II)
  • Serum + urine electrophoresis, free light chains
  • HCV / HBV / HIV serology + HCV viral load
  • ANA, ENA, anti-Ro/La (Sjögren), CT chest/abdo (lymphoma screen)
  • Bone marrow if monoclonal band

BIOPSY (definitive):

  • MPGN pattern (lobular, double contours)
  • INTRACAPILLARY PSEUDOTHROMBI (PAS+ deposits)
  • IF: IgM, IgG, C3 deposits
  • EM: subendothelial deposits with curved microtubular substructure
  • Vasculitis of small renal arteries

Treatment by aetiology

HCV-ASSOCIATED (type II, commonest):

  • Direct-acting antivirals first-line
  • Sofosbuvir/velpatasvir 400/100 mg daily 12 weeks (pan-genotypic)
  • Glecaprevir/pibrentasvir alternative (avoid in eGFR < 30 — drug-specific updates)
  • > 95% SVR; majority of GN resolves with viral cure
  • If severe (RPGN, nephrotic): add rituximab BEFORE antivirals

Severe / Rapidly Progressive Gn

  • Methylprednisolone 500–1000 mg IV × 3 days
  • Rituximab 375 mg/m² weekly × 4 (preferred to cyclophosphamide)
  • Plasma exchange daily 7–14 sessions if pulmonary haemorrhage, severe AKI, or hyperviscosity
  • Then DAAs once stabilised (HCV cases)

Non-hcv / Idiopathic

  • Treat associated autoimmune disease / lymphoma
  • Rituximab for relapsing or severe disease
  • Maintenance with low-dose steroid or azathioprine

TYPE I (monoclonal):

  • Treat underlying plasma cell / lymphoid clone
  • Myeloma protocol (bortezomib/lenalidomide)
  • Waldenström (rituximab + ibrutinib)

Monitoring

  • Cryocrit, C4, eGFR, urine ACR every 1–3 months
  • HCV viral load at SVR12
  • Surveillance for lymphoma in type II disease (~ 5–10% lifetime risk)

UK Pathway

  • Renal MDT + hepatology + haematology + rheumatology
  • National Renal Vasculitis network for severe disease
MPGN & C3 Glomerulopathy
Related reading: MPGN & C3 Glomerulopathy.

Key practical tips

Designed for quick scanning — what to order, what to avoid, sensible portions, common mistakes.

  • Take prescribed ACE inhibitor / ARB / SGLT2 inhibitor consistently — diet works alongside, not instead
  • Monitor BP at home weekly
  • Review urine ACR with your team to track progress

Clinical guidance

TL;DR summary

MPGN with intracapillary pseudothrombi. Mixed (type II/III) drives most renal disease; HCV is the dominant cause. Treat the trigger: DAAs cure HCV-related disease in > 95%. Add rituximab ± PLEX for severe vasculitis.

Key takeaways
  • Type II mixed cryoglobulinaemia + HCV = classic.
  • Very low C4 with normal-low C3 is the bloods clue.
  • Biopsy: MPGN with intracapillary 'pseudothrombi'.
  • DAAs first-line for HCV; > 95% SVR.
  • Severe GN/vasculitis: rituximab ± plasma exchange.
Kidney Diet & Nutrition Considerations

When protein is leaking into the urine, the goal is to protect the remaining kidney function. Dietary protein should be sensible — neither very high nor unnecessarily low — and a Mediterranean-style plate with reduced salt supports both blood pressure and albuminuria reduction alongside ACE inhibitors, ARBs or SGLT2 inhibitors.

Foods to prioritise

  • Plant proteins: beans, lentils, tofu, tempeh, chickpeas
  • Vegetables, fruit and whole grains
  • Oily fish 1–2 times a week
  • Olive oil as the main cooking fat

Foods to limit

  • Added salt (≤ 6 g/day)
  • Processed meats and high-additive ready meals
  • Excess animal protein at every meal

Potassium, phosphate and protein needs vary between individuals — please confirm personal targets with your renal team or dietitian. Browse the Kidney Diet Hub for more guides in this cluster.

Frequently asked questions

What is cryoglobulinaemic GN?

Cryoglobulins are immunoglobulins that precipitate at temperatures below 37°C and redissolve on warming. Cryoglobulinaemic glomerulonephritis is immune-complex-mediated glomerular injury with a membranoproliferative (MPGN) pattern. It is most often caused by mixed cryoglobulins (type II or III) associated with hepatitis C, B-cell lymphoma, autoimmune disease (Sjögren, lupus, RA) or, rarely, idiopathic.

What are types I, II and III?

TYPE I: monoclonal Ig (usually IgM or IgG) — multiple myeloma, Waldenström, MGUS. TYPE II (mixed): monoclonal IgM with rheumatoid factor activity + polyclonal IgG — HCV in 80%, also lymphoma, Sjögren. TYPE III (mixed): polyclonal IgM + polyclonal IgG — connective tissue disease, chronic infection. Renal involvement is commonest with TYPE II.

How does it present?

Skin (palpable purpura on legs in 90%), arthralgia, peripheral neuropathy (Meltzer triad) plus kidney: proteinuria (often nephrotic), microscopic haematuria, hypertension, AKI in 25%. Bloods: very low C4 (classical complement), normal-low C3, positive rheumatoid factor, monoclonal band on serum electrophoresis, cryocrit > 1%. Biopsy: type I MPGN pattern with intracapillary 'pseudothrombi' (microtubular cryoglobulin deposits), C3 and IgM staining.

How is it treated?

Treat the underlying cause: HCV → direct-acting antivirals (DAAs — sofosbuvir/velpatasvir 12 weeks) achieve > 95% sustained virological response and often resolve renal disease without immunosuppression. Severe/active disease (rapidly progressive GN, severe vasculitis): add rituximab 375 mg/m² weekly × 4 ± plasma exchange ± methylprednisolone. AVOID interferon (worsens nephritis). Lymphoma-associated: treat the lymphoma. Type I: target the clonal plasma cell/lymphoid disorder.

Can diet reduce protein in urine?

A reduced-salt, Mediterranean-style diet with sensible protein intake can lower urine protein, particularly when combined with prescribed ACE inhibitors, ARBs or SGLT2 inhibitors. Very low-protein diets are not routinely recommended without dietitian supervision.

Nutritional challenges in kidney disease

Many people living with kidney disease have to limit foods because of potassium, phosphate, diabetes, dialysis, appetite changes or simply the time it takes to cook from scratch every day. That can make it harder to keep daily nutrition balanced — particularly for vitamins and minerals that food alone may not fully cover.

Kidney Vitality is a UK-formulated daily nutritional support product designed by Consultant Nephrologist Professor Mohammed Mahdi Althaf with renal nutrition in mind from the start. It keeps doses moderate, leaves out added potassium, phosphate and magnesium, and avoids megadose vitamin A — sitting alongside a kidney-friendly diet, not replacing it.

Why Kidney Vitality fits this need

Built around UK guidance

Aligned with KDIGO 2024 GN guideline, EASL HCV management 2023, BSR vasculitis guidance and UK Hepatitis C Elimination Strategy.

Designed by a UK Consultant Nephrologist

Formulated and reviewed by Professor Mohammed Mahdi Althaf (GMC 7216325).

Aetiology-led & MDT-focused

Practical step-up from DAAs alone to rituximab and plasma exchange for severe disease.

Designed by a UK Consultant Nephrologist

Ready to support your kidney health?

If you have been researching kidney health, supplements, CKD nutrition or kidney-friendly living, Kidney Vitality was developed specifically around those principles by Professor Mohammed Mahdi Althaf (GMC 7216325). Nephrologist Developed Daily Multivitamin.

  • No Added Potassium
  • No Added Magnesium
  • No Added Phosphorus
  • No Added Iron
  • One capsule daily
  • UK GMP — BRCGS, NSF GMP, Halal
Subscribe & Save — £20.39/monthCheck your current multivitamin

✓ Free UK tracked delivery  ·  ✓ Delivered every 30 days  ·  ✓ Pause or cancel anytime  ·  ✓ Never run out

ComparisonKidney VitalityTypical high-street multivitamin
Added potassiumNoneOften included
Added phosphateNoneOften included (E338–E452)
Vitamin A (retinol)No megadoseOften high-dose retinol
Kidney-focused formulationYesNo — general population
Consultant Nephrologist involvementYes (GMC 7216325)No
UK GMP manufacturedYes (BRCGS, NSF GMP)Varies

Food supplement. Not a medicine and not a treatment for kidney disease. Speak with your GP, pharmacist or renal team before starting any new supplement, especially in advanced CKD, on dialysis, post-transplant, pregnant or breastfeeding.

Clinical reviewer

Professor Mohammed Mahdi Althaf

Consultant Nephrologist

Acute Physician

GMC 7216325

View Full Biography

Professor Mohammed Mahdi Althaf is a UK Consultant Nephrologist and Acute Physician with a special interest in chronic kidney disease, AKI prevention and renal nutrition. He combines hospital practice with patient education and clinical guidance review.

View professional profile →
View Credentials
  • MD
  • MSc
  • PgDip (Clin Ed)
  • FRCP
  • FHEA
  • FASN

About this article

Written for UK patients and based on:

  • NICE guidance
  • NHS resources
  • British Dietetic Association guidance
  • Kidney Care UK resources
View methodology

Each article is researched against current UK clinical guidance (NICE NG203, NG118, NG136), NHS patient resources, KDIGO and KDOQI international guidelines, and the British Dietetic Association Renal Nutrition Group. Drafts are written by the Kidney Vitality editorial team and reviewed by a UK Consultant Nephrologist before publication. Content is reviewed on a rolling basis and updated when guidance changes.

Editorial standards

  • Clinically reviewed
  • NHS-aligned
  • NICE-aligned
  • Evidence-based
  • Reviewed before publication
View full editorial process

Every article is researched and written by the Kidney Vitality editorial team using current UK clinical guidance (NICE NG203, NG118, NG136), NHS patient resources, KDIGO/KDOQI international guidelines, and British Dietetic Association renal nutrition guidance. Drafts are reviewed for clinical accuracy by Professor Mohammed Mahdi Althaf, MD, MSc, PgDip (Clin Ed), FRCP, FHEA, FASN (Consultant Nephrologist & Acute Physician, GMC 7216325) before publication. Content is updated when UK guidance changes.

References (4)View Sources
  1. NICE NG203: Chronic kidney disease — assessment and management
  2. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD
  3. KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update
  4. British Dietetic Association — Renal Nutrition Group

Medical disclaimer

This content is educational only and does not replace personalised medical advice.

Read full disclaimer

This page is general information, not personal medical advice. If you have chronic kidney disease, are on dialysis, have had a kidney transplant, are pregnant or breastfeeding, or take prescription medication, please confirm any supplement with your GP, pharmacist or renal team before starting.

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