Glomerular disease · KIMS Secunderabad
Amyloidosis and the Kidneys — How Protein Deposits Damage Kidney Function
Amyloidosis is a disease caused by the abnormal folding and extracellular deposition of proteins — called amyloid fibrils — in organs and tissues throughout the body. The kidneys are among the most commonly and most seriously affected organs. Amyloid fibril deposits accumulate in the glomeruli, vessels, and tubules of the kidney, disrupting normal architecture and function. The result is progressive proteinuria, often reaching nephrotic range, followed by declining eGFR and ultimately kidney failure if the underlying amyloid-producing process is not treated.
Amyloidosis is diagnosed by tissue biopsy — the amyloid deposits have a characteristic appearance under polarised light after staining with Congo red (apple-green birefringence) and a specific fibrillar structure on electron microscopy. Kidney biopsy with the full three-component analysis — light microscopy, immunofluorescence, and electron microscopy — performed in KIMS's NABL-accredited laboratory provides both the diagnosis of amyloidosis and the typing information (which amyloid protein is responsible) that determines the treatment.
Types of amyloidosis affecting the kidneys
AL amyloidosis (primary amyloidosis) — the most common type in India
AL amyloidosis is caused by a plasma cell dyscrasia — a clonal population of plasma cells in the bone marrow produces abnormal immunoglobulin light chains (lambda more often than kappa in AL amyloidosis) that misfold and deposit as amyloid fibrils. AL amyloidosis is closely related to multiple myeloma — approximately 15% of patients with AL amyloidosis have overt myeloma, and the remainder have a plasma cell clone producing the amyloid-forming light chain without meeting the criteria for myeloma. The kidneys (60 to 70% of AL patients), heart (50%), liver (25%), peripheral and autonomic nerves (20%), and soft tissues are the most commonly affected organs. AL amyloidosis is treated by suppressing the plasma cell clone responsible for producing the amyloid-forming light chain — using chemotherapy regimens including bortezomib (a proteasome inhibitor) combined with cyclophosphamide and dexamethasone (CyBorD), or daratumumab-based regimens. High-dose melphalan with autologous stem cell transplantation is used in eligible patients. The goal is to achieve a haematological response — reduction in the abnormal light chain — which halts further amyloid deposition and allows existing deposits to slowly resorb.
AA amyloidosis (secondary amyloidosis)
AA amyloidosis is caused by the deposition of serum amyloid A protein — an acute phase reactant produced by the liver in response to chronic inflammation. It complicates chronic inflammatory conditions: rheumatoid arthritis, inflammatory bowel disease (Crohn's disease, ulcerative colitis), chronic infections (tuberculosis — particularly important in India, osteomyelitis, bronchiectasis), familial Mediterranean fever, and autoinflammatory disorders. The kidney is the predominantly affected organ in AA amyloidosis. Treatment is directed at suppressing the underlying inflammatory or infectious condition — reducing the SAA level halts amyloid deposition and can stabilise or improve kidney function.
Other types — hereditary and dialysis-related
Hereditary (familial) amyloidosis from mutations in transthyretin (ATTR), fibrinogen A alpha-chain (AFib), apolipoprotein A1 (AApoA1), and other proteins can affect the kidneys — though cardiac and neurological involvement is more prominent in ATTR amyloidosis. Dialysis-related amyloidosis (DRA) — beta-2 microglobulin accumulation in long-term dialysis patients — affects primarily joints and bones rather than the kidneys.
Clinical presentation — what amyloidosis looks like in the kidney
Nephrotic syndrome — heavy proteinuria (above 3.5 g/day), hypoalbuminaemia, and oedema. This is the most common presentation of renal amyloidosis. Amyloid deposits in the glomeruli disrupt the filtration barrier, causing massive protein leakage. The protein leakage may precede any fall in eGFR by months to years.
Organomegaly — enlarged kidneys on ultrasound are characteristic of early renal amyloidosis (kidneys are typically small in most other causes of CKD). Hepatomegaly from hepatic amyloid may accompany kidney involvement in AL amyloidosis.
Progressive CKD — eGFR declines as amyloid replaces functional glomerular and tubular tissue. The rate of decline depends on the amyloid type and the response to treatment.
Associated organ findings in AL amyloidosis — macroglossia (tongue enlargement — virtually pathognomonic), carpal tunnel syndrome, periorbital purpura (bleeding around the eyes from amyloid vascular deposition), postural hypotension (autonomic neuropathy), and cardiac involvement (restrictive cardiomyopathy — the most important determinant of prognosis in AL amyloidosis).
Diagnosis at KIMS — the essential role of kidney biopsy
Serum and urine protein electrophoresis (SPEP/UPEP) and free light chain assay
In AL amyloidosis, the abnormal light chain may be detected as a monoclonal band (M-protein) on electrophoresis or as an elevated free light chain ratio. Sensitivity is approximately 90% for detecting the underlying plasma cell clone. Bone marrow biopsy confirms the plasma cell clone.
SAA protein level (for AA amyloidosis)
Elevated serum amyloid A level in the context of a chronic inflammatory condition suggests AA amyloidosis as the underlying mechanism. Used both to support the diagnosis and to monitor treatment response, since reducing SAA halts amyloid deposition in AA amyloidosis.
Kidney biopsy with NABL LM + IF + EM at KIMS
The definitive diagnostic test for renal amyloidosis — confirming that the deposits are amyloid and characterising the amyloid type. Light microscopy (LM) — amyloid appears as amorphous, eosinophilic, homogeneous material deposited in the glomeruli (mesangium and capillary walls), vessels, and tubular basement membranes. Congo red staining — performed on paraffin-fixed tissue — shows the characteristic apple-green birefringence under polarised light that is diagnostic of amyloid. This is the specific confirmatory stain for amyloidosis. Immunofluorescence (IF) — staining with antibodies against specific amyloid proteins (lambda, kappa light chains, SAA, transthyretin) types the amyloid. Lambda light chain restriction in the deposits indicates AL amyloidosis (lambda type). SAA staining indicates AA amyloidosis. Electron microscopy (EM) — amyloid fibrils are 8 to 12nm in diameter, randomly arranged, unbranched — the ultrastructural appearance that distinguishes amyloid from other extracellular matrix deposits. EM is performed in-house at KIMS NABL laboratory.
Why Congo red staining in-house matters
Congo red staining under polarised light is the most specific diagnostic test for amyloidosis — the apple-green birefringence is pathognomonic. This staining is performed in-house in KIMS's NABL-accredited pathology laboratory. Many centres in Hyderabad outsource Congo red staining or do not have the polarised microscopy required to read the result accurately. At KIMS, the full amyloid workup — Congo red, immunofluorescence typing, and EM — is performed in the same laboratory.
Treatment at KIMS — suppressing the amyloid-producing process
AL amyloidosis — suppress the plasma cell clone
CyBorD (cyclophosphamide + bortezomib + dexamethasone) · Daratumumab-based regimens for relapsed/refractory disease · High-dose melphalan + autologous stem cell transplant in eligible patients (ECOG PS 0–1, no significant cardiac amyloid) · Coordination with haematology-oncology for chemotherapy administration. Goal: achieve a haematological response — reduction in the abnormal light chain — which halts further amyloid deposition and allows existing deposits to slowly resorb.
AA amyloidosis — suppress the underlying inflammation
Treat the cause: anti-TNF or anti-IL-6 therapy for rheumatoid arthritis and inflammatory bowel disease · Anti-tuberculosis treatment for TB-associated AA · Colchicine for familial Mediterranean fever. Response monitored by SAA protein level reduction — falling SAA halts amyloid deposition and can stabilise or improve kidney function.
All types — supportive kidney care
ACE inhibitor or ARB for proteinuria reduction · Diuretics for oedema · Sodium restriction · Anticoagulation for nephrotic syndrome with very low albumin (below 20 g/L) — high thrombosis risk · Statins (paradoxically, hypercholesterolaemia in nephrotic syndrome does not have the same cardiovascular risk as primary hypercholesterolaemia, but lipid management is still appropriate).
ESRD from amyloidosis — renal replacement therapy
Haemodialysis · Peritoneal dialysis · Kidney transplant — considered in patients with AL amyloidosis who have achieved a sustained haematological response and in AA amyloidosis where the underlying condition is well-controlled.
Book a Nephrology Consultation for Amyloidosis at KIMS — Congo Red Biopsy and Full Workup Available
Frequently Asked Questions — Amyloidosis and Kidney Disease
Amyloidosis is a disease where abnormal proteins — called amyloid fibrils — are produced in the body and deposited in organs instead of being broken down normally. Think of it as a garbage disposal problem: a specific type of misfolded protein accumulates in organs rather than being cleared. When these deposits accumulate in the kidneys, they block the kidney's filtering units (glomeruli) and cause protein to leak into the urine (proteinuria), then progressively damage kidney function. The type of amyloid determines the cause and the treatment — AL amyloidosis comes from a bone marrow plasma cell abnormality; AA amyloidosis comes from chronic inflammation or infection.
The earliest clinical sign is proteinuria — protein in the urine. This often presents first as frothy or foamy urine (from heavy protein content), which the patient may notice before any laboratory testing is done. As proteinuria becomes heavier (above 3.5 grams per day — nephrotic range), oedema develops — first around the ankles and then spreading. The kidneys may actually appear enlarged on ultrasound in early amyloidosis (unlike most kidney diseases, which cause kidney shrinkage). Fatigue and weight loss may accompany the kidney symptoms, particularly in AL amyloidosis where other organs (heart, liver, nerves) are also affected.
Amyloidosis is diagnosed by biopsy — the abnormal protein deposits must be seen and stained in tissue. Kidney biopsy is the preferred biopsy site when the kidneys are clinically involved (heavy proteinuria, declining eGFR). The tissue is stained with Congo red — which causes amyloid deposits to appear apple-green under polarised light, a virtually specific finding. Immunofluorescence typing then identifies which amyloid protein is responsible (lambda or kappa light chain for AL; SAA for AA). Electron microscopy confirms the fibrillar structure of the deposits. In patients where kidney biopsy is high-risk, abdominal fat pad biopsy or rectal biopsy (both safer and less invasive sites where amyloid frequently deposits) can provide a diagnosis, though with lower sensitivity than kidney biopsy.
AL amyloidosis is caused by a plasma cell clone — the same type of abnormal cells that cause multiple myeloma — but AL amyloidosis is not itself classified as cancer. The plasma cell clone in AL amyloidosis is typically small and does not meet the criteria for myeloma (which requires a specific degree of bone marrow plasma cell infiltration or end-organ damage from the myeloma itself). However, the treatment of AL amyloidosis uses the same chemotherapy agents used for myeloma — bortezomib, cyclophosphamide, daratumumab — to suppress the plasma cell clone. AA amyloidosis is not related to cancer — it is caused by chronic inflammation or infection.
AL amyloidosis cannot currently be cured in the traditional sense, but sustained remission — halting further amyloid deposition and allowing gradual resorption of existing deposits — is achievable. Achieving a complete haematological response (undetectable light chain level) correlates with improved organ function and prolonged survival. For AA amyloidosis, complete control of the underlying inflammatory or infectious condition can halt amyloid deposition and allow kidney function to stabilise or improve. Kidney function rarely returns to completely normal — the existing amyloid deposits resolve slowly — but further deterioration stops if the underlying disease is controlled.
AL amyloidosis and multiple myeloma share the same underlying pathology: a clonal population of abnormal plasma cells in the bone marrow producing immunoglobulin. In myeloma, the clone produces excess immunoglobulin or light chains that cause bone destruction, hypercalcaemia, anaemia, and kidney damage from cast nephropathy. In AL amyloidosis, the clone produces a specific type of light chain that misfolds and deposits as amyloid fibrils — causing organ damage through tissue infiltration rather than the mechanisms of myeloma. Approximately 15% of AL amyloidosis patients also meet the criteria for overt myeloma. The treatments overlap significantly — bortezomib-based regimens are used for both.
Kidney recovery in AL amyloidosis depends on achieving a rapid and deep haematological response — suppressing the light chain to undetectable levels. With complete haematological response, proteinuria often improves significantly over 6 to 18 months, and eGFR may stabilise or modestly improve. The kidneys are unlikely to return to completely normal function if significant amyloid has already deposited, but halting the progression is clinically meaningful — the difference between stable CKD and progressive decline to dialysis. In AA amyloidosis, kidney function can recover more substantially if the underlying inflammation is completely suppressed, particularly when treatment is started before significant glomerular sclerosis has occurred.
KIMS Secunderabad — Dr. Aswini Dutt T (glomerular disease subspecialty), NABL-accredited kidney biopsy with Congo red staining under polarised light, immunofluorescence typing (lambda, kappa, SAA, transthyretin), and electron microscopy — all in-house. Free light chain assay and SPEP/UPEP. Haematology coordination for AL amyloidosis treatment. AA amyloidosis workup including SAA protein level and underlying disease evaluation. Transplant programme for amyloidosis ESRD in remission. Call 040-4488-5000.