What is amyloidosis?
Amyloidosis is a group of diseases where specific proteins misfold into beta-sheet fibrils that deposit as insoluble amyloid in organs, disrupting function.
Types Affecting Kidneys
1. AL (immunoglobulin LIGHT chain) amyloidosis:
- Cause: a plasma cell clone in the bone marrow produces an abnormal light chain that misfolds
- ~600 new cases per year in UK
- Median age 65
- Often involves multiple organs: kidneys (70%), heart (70%), liver, nerves, soft tissues
2. AA (Serum Amyloid A) amyloidosis:
- Cause: long-standing inflammation raises SAA, which over years deposits as amyloid
- Underlying causes:
- Rheumatoid arthritis (now rare in biologic era)
- Inflammatory bowel disease
- Familial Mediterranean fever (FMF)
- Chronic infections (osteomyelitis, bronchiectasis, TB)
- Castleman disease
- Kidney involvement very common (~90%)
3. HEREDITARY AMYLOIDOSES (rare):
- ATTR (transthyretin) — usually heart and nerves; kidney involvement rare
- Fibrinogen A-alpha-chain — kidney predominant
- Apolipoprotein A1, A2, lysozyme — kidney variants
- Genetic testing essential — wrong treatment otherwise
4. DIALYSIS-RELATED (β2-microglobulin):
- Old dialysis-related amyloid (joints) — now rare with modern membranes
Symptoms and diagnosis
RED FLAGS for amyloidosis:
- Heavy proteinuria (often > 5 g/day) with NORMAL-SIZED or ENLARGED kidneys
- Unexplained heart failure or thickened heart on echo
- Carpal tunnel syndrome (often bilateral, predates renal disease)
- Macroglossia (enlarged tongue) — AL specific
- Periorbital purpura ('raccoon eyes') after coughing/straining — AL
- Easy bruising
- Weight loss
- Postural hypotension
- Hepatomegaly without obvious cause
Investigations
- Urine ACR (often very high)
- Serum and urine immunoglobulin free light chains (kappa/lambda ratio abnormal in AL)
- Serum protein electrophoresis + immunofixation
- NT-proBNP and troponin (cardiac involvement)
- ECG (low voltages, pseudo-infarct pattern)
- Echocardiogram
- Serum SAA (raised in AA)
- CRP, ESR
Kidney Biopsy
- CONGO RED stain → apple-green birefringence under polarised light = diagnostic
- Type the amyloid:
- Immunohistochemistry on biopsy (kappa, lambda, SAA)
- LASER CAPTURE + MASS SPECTROMETRY at the National Amyloidosis Centre — gold standard
Whole-body Amyloid Load
- SAP (serum amyloid P component) scintigraphy at NAC, Royal Free Hospital London
- Cardiac MRI
- DPD scan for ATTR
ALL UK PATIENTS WITH SUSPECTED AMYLOIDOSIS SHOULD BE REFERRED TO THE NATIONAL AMYLOIDOSIS CENTRE (Royal Free, London) — free, NHS-funded one-stop assessment.
Kidney Vitality is a daily multivitamin developed by a UK Consultant Nephrologist using renal nutrition principles. It contains no added potassium, magnesium, phosphorus or iron, and no herbal blends. See the formulation.
Treating AL amyloidosis
GOAL: suppress the abnormal plasma cell clone so production of toxic light chains stops. Amyloid deposits then slowly resorb in some organs.
FIRST-LINE THERAPY (UK NHS since 2021):
- DARATUMUMAB + bortezomib + cyclophosphamide + dexamethasone (DARA-VCD)
- ANDROMEDA trial showed dramatic improvement
- Subcutaneous daratumumab is well tolerated
- Aim for haematological complete response (kappa/lambda ratio normalises, free light chains < 20)
Second-line Or Refractory
- Lenalidomide-based therapy
- Ixazomib (oral)
- Venetoclax (in t(11;14)+ disease)
- Carfilzomib
Autologous Stem Cell Transplant (Asct)
- Considered for younger, fitter patients with limited organ involvement
- High-dose melphalan + stem cell rescue
- Mortality risk 3-5% in best centres — careful selection essential
- Often used as consolidation after good initial response
Supportive
- Diuretics for oedema (often huge doses needed)
- Avoid ACE/ARB if low BP
- Anticoagulation if albumin < 20 g/L
- Compression stockings
- Cardiology input (heart involvement drives mortality)
- Renal team input (proteinuria, eGFR, fluid)
Outlook
- Median survival now 5+ years (was 1-2 years pre-novel agents)
- Cardiac involvement is the dominant prognostic factor
- Kidney response (50% drop in proteinuria) often takes 12 months
Treating AA amyloidosis
GOAL: identify and suppress the underlying chronic inflammation. When SAA falls below ~10 mg/L sustainably, amyloid deposition stops and slow resorption begins.
Treat Underlying Cause
- Rheumatoid arthritis → biologics (anti-TNF, tocilizumab, JAK inhibitors)
- Inflammatory bowel disease → biologics, surgery
- Familial Mediterranean fever → COLCHICINE (lifelong, very effective)
- Chronic infection → antibiotics, source control (drain abscess, treat osteomyelitis)
- Bronchiectasis → optimise lung care
- TRAPS, CAPS, hyper-IgD → IL-1 blockers (anakinra, canakinumab)
Specific Anti-amyloid Therapy
- Tocilizumab (IL-6 blocker) — useful even in non-rheumatic causes
- Eprodisate (in trials) — blocks amyloid assembly
- CPHPC + anti-SAP antibody — investigational (NAC research)
Supportive
- ACE inhibitor for proteinuria
- Diuretics
- Statin
- Bone protection if steroids
- Avoid NSAIDs (worsen kidney and gut)
Monitoring
- Serum SAA every 1-3 months (target < 10 mg/L)
- Urine ACR
- Creatinine, eGFR
- Annual SAP scintigraphy at NAC
Outlook
- Variable — depends on underlying disease control
- With good inflammation control, kidney function can stabilise for many years
- Untreated: progressive kidney failure within 5-10 years
Living with amyloidosis and longer term
Daily
- Take medications consistently
- Daily weight, BP at home
- Low salt diet < 5 g/day
- Adequate protein (don't restrict — you lose protein in urine)
- Avoid NSAIDs lifelong
Key Appointments
- NAC at Royal Free annually (or 6-monthly initially)
- Haematology (AL) or rheumatology/gastro (AA) regularly
- Renal clinic every 1-3 months initially
- Cardiology if heart involvement
Dialysis
- Considered when CKD reaches stage 5
- AL amyloid: dialysis tolerated less well due to cardiac and autonomic involvement; haemodialysis often poorly tolerated, PD may be better
- AA amyloid: dialysis usually tolerated well
- Patient-centred decision
Kidney Transplant
- AL: only after good haematological response sustained 1-2 years; recurrence risk
- AA: feasible once underlying inflammation controlled; recurrence rare if SAA suppressed
- Discuss carefully with NAC and transplant team
Mental Health
- Amyloidosis diagnosis is overwhelming
- Specialist nurse support at NAC
- Patient organisation: Amyloidosis UK
- Discuss financial support and benefits (often eligible for PIP)
