Renal Amyloidosis
Amyloidosis is the extracellular deposition of insoluble fibrils formed from misfolded proteins. The fibrils have a beta-pleated sheet structure, resist breakdown and progressively disrupt organ function. The kidney is one of the most often affected organs, mainly in AL and AA amyloidosis. Histological hallmark: Congo red staining with apple-green birefringence under polarised light.
Types relevant to the kidney
Renal involvement
- Glomerular deposits (mesangium and capillary walls) are the usual pattern → nephrotic syndrome with heavy proteinuria, hypoalbuminaemia, oedema and hyperlipidaemia. The urine sediment is usually bland (little haematuria).
- Ultrasound – kidneys normal-sized or enlarged even when function is reduced (as in diabetic nephropathy)
- Course – progressive CKD to end-stage renal disease. Hypertension is less common than in other glomerular diseases; orthostatic hypotension may occur (autonomic neuropathy, cardiac involvement).
- Less often – vascular or tubulointerstitial deposits: renal impairment with little proteinuria, nephrogenic diabetes insipidus (polyuria), renal tubular acidosis
Extrarenal features
- Heart (mainly AL, also transthyretin) – restrictive cardiomyopathy with thick ventricular walls but a low-voltage ECG; heart failure with preserved ejection fraction, arrhythmias, syncope
- AL clues – macroglossia and periorbital purpura ("raccoon eyes"), easy bruising (acquired factor X deficiency)
- Liver and spleen – hepatosplenomegaly, raised alkaline phosphatase
- Nerves – peripheral sensory neuropathy, autonomic neuropathy (orthostatic hypotension, impotence, diarrhoea), carpal tunnel syndrome
- GI tract – malabsorption, diarrhoea, bleeding, weight loss
Diagnosis
- Urine – proteinuria (24-hour urine or protein/creatinine ratio), mainly albumin
- Screening for AL – serum and urine protein electrophoresis with immunofixation, plus serum free light chains (kappa/lambda ratio); bone marrow biopsy to assess the plasma-cell clone. A monoclonal protein alone does not prove AL – it is common in older people (MGUS).
- Tissue biopsy with Congo red – abdominal fat pad aspirate (simplest), rectal biopsy or bone marrow; kidney biopsy when these are negative and renal disease is present. Electron microscopy: randomly arranged, non-branching fibrils about 10 nm wide.
- Typing – immunohistochemistry (kappa, lambda, serum amyloid A) or mass spectrometry, which is the most reliable method
- Cardiac assessment – ECG, echocardiography (thick walls, diastolic dysfunction), cardiac MRI, NT-proBNP and troponin (used to stage AL)
- Nephrotic syndrome in a patient over 50 with heart failure, a low-voltage ECG or a monoclonal protein – suspect AL amyloidosis and assess the heart urgently