Renal Amyloidosis
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Direct answer
Apple-green birefringence under polarised light after Congo red staining is the diagnostic moment in renal amyloidosis: beta-pleated sheet fibrils laid down in the mesangium and vessel walls, producing nephrotic-range proteinuria in kidneys that are often normal-sized or enlarged when every other chronic disease has shrunk them. What happens next depends entirely on typing, because two diseases wear the same stain. AL amyloidosis — a plasma cell disorder depositing light-chain fragments, lambda more than kappa — demands haematology with bortezomib-based chemotherapy, while AA amyloidosis deposits serum amyloid A from chronic inflammation, and in Indian practice that inflammation is still, characteristically, tuberculosis, leprosy or chronic osteomyelitis rather than the rheumatoid and inflammatory bowel disease of Western textbooks.
What you must remember
- The stain: Congo red, apple-green under polarised light; the fibrils are beta-pleated sheets — the chemistry behind the exam question.
- AL phenotype: nephrotic proteinuria with restrictive cardiomyopathy, painful peripheral and autonomic neuropathy, macroglossia and periorbital purpura — the last two nearly specific and heavily tested.
- AL work-up: serum free light chains with ratio, serum and urine electrophoresis with immunofixation, then bone marrow; NT-proBNP and troponin stage prognosis (Mayo system).
- Typing matters absolutely: laser microdissection with mass spectrometry is the modern standard; treating AA disease with myeloma chemotherapy, or AL disease with anti-inflammatory therapy, is a catastrophic category error.
- AA causes — Indian pattern: pulmonary and abdominal tuberculosis, lepromatous leprosy, chronic osteomyelitis and suppurative lung disease; globally, rheumatoid arthritis, inflammatory bowel disease and familial Mediterranean fever, where colchicine prevents amyloidosis outright.
- Screening biopsy: fat pad or rectal biopsy is positive in roughly 70–80 per cent of systemic AL disease — useful when the kidney biopsy is delayed or contraindicated.
- Dialysis-related amyloidosis: beta-2 microglobulin deposition after years on dialysis, presenting as carpal tunnel syndrome and destructive spondyloarthropathy — a distinct entity, not a variant of AL.
- Transplant caution: AL disease recurs in the graft if the clone persists, so haematological response precedes renal listing where possible.
Two patients, one stain, opposite treatments
A 58-year-old man presents with six months of oedema: proteinuria 9 g/day, albumin 22 g/L, creatinine 1.3 mg/dL, an echocardiogram showing a thickened, restrictive left ventricle, and a tongue that fills the mouth. The kidney biopsy reports Congo-red-positive amyloid; immunofluorescence favours lambda; serum free light chains return 480 mg/L with a heavily skewed ratio. His pathway runs to haematology — bortezomib, dexamethasone and daratumumab, the ANDROMEDA backbone — with cardiac staging by NT-proBNP and troponin deciding both intensity and honesty of the prognosis conversation; his kidney survives only if the clone is silenced. Across the ward, a 40-year-old with two decades of chronic discharging osteomyelitis of the tibia has identical birefringence on biopsy and a free light chain panel that is normal. His treatment is surgical: eradicate the infection, suppress the serum amyloid A drive, and watch the proteinuria fall over months — amyloid can regress when the stimulus dies, a point the viva examiner rewards. The two biopsies are indistinguishable to the eye; the mass spectrometer and the clinic chart separate them, and every prescribing decision hangs on that separation.
How the examiner frames it
The stems are built on the discriminating signs. Nephrotic syndrome plus a giant tongue or periorbital purpura after proctoscopy or pinching — "raccoon eyes" — is AL until disproven, and the free light chain assay is the next investigation, not another biopsy. Nephrotic syndrome in a patient with chronic tuberculosis, leprosy or bronchiectasis is AA, and the exam answer is treat the underlying inflammation. The imaging twist appears regularly: kidneys that are large or normal-sized on ultrasound in a nephrotic patient nudge toward amyloidosis and myeloma, against the small kidneys of most chronic disease. One caution is worth voicing in the viva — Congo red positivity names the disease, never the type; quoting "AL until typed, by mass spectrometry where available" marks you as someone who has actually sat in a nephropathology meeting.
Frequently asked questions
Which stain confirms amyloid, and what is seen?
Congo red with apple-green birefringence under polarised light; the fibrils are beta-pleated sheets.
Why is typing mandatory after a positive Congo red?
AL and AA amyloid share the stain but demand opposite treatments — chemotherapy for the plasma cell clone, infection or inflammation control for AA.
What screens for AL amyloidosis?
Serum free light chains with ratio, electrophoresis with immunofixation of serum and urine, and bone marrow examination; cardiac assessment by NT-proBNP, troponin and echocardiography.
Which chronic diseases drive AA amyloidosis in India?
Tuberculosis, lepromatous leprosy, chronic osteomyelitis and suppurative lung disease — infection-dominated, unlike the rheumatoid and IBD-driven pattern of Western series.
Which organs suggest AL rather than AA at the bedside?
Macroglossia, periorbital purpura, restrictive cardiomyopathy and painful autonomic neuropathy — nearly specific for AL.
What is dialysis-related amyloidosis?
Beta-2 microglobulin deposition after years on dialysis, causing carpal tunnel syndrome and arthropathy — resolved by transplantation more than by any dialysis prescription.