Types of Amyloidosis
This form of systemic amyloidosis arises from misfolded monoclonal light chains, most often λ, produced by a plasma-cell dyscrasia
What is AL (light-chain) amyloidosis?
This classically describes the shared secondary structure of amyloid fibrils, characterized by stacked peptide strands stabilized by intermolecular hydrogen bonds.
What is a β-pleated sheet?
This organ, aside from the kidney, is most frequently involved in AL amyloidosis and is the leading cause of mortality in affected patients.
What is the heart?
This classic renal manifestation of amyloidosis is defined by heavy proteinuria, hypoalbuminemia, and edema
What is nephrotic syndrome?
This special stain, when viewed under polarized light, reveals the pathognomonic apple-green birefringence of amyloid deposits in renal tissue
What is Congo red staining?
This type results from serum amyloid A deposition and classically occurs in chronic inflammatory conditions such as rheumatoid arthritis or IBD
What is AA (secondary) amyloidosis?
In AL amyloidosis, this type of protein produced by a clonal plasma cell population is the precursor to amyloid fibrils that deposit in the kidney.
What are immunoglobulin light chains?
This diagnostic blood test is essential for detecting a monoclonal protein and raising suspicion for AL amyloidosis
What is serum protein electrophoresis (looking for an M-spike)?
In amyloidosis-related nephrotic syndrome, this laboratory finding is typically present despite bland urinary sediment and absence of casts.
What is massive proteinuria?
On light microscopy, amyloid deposits in the glomeruli typically appear as this type of material, which is acellular and periodic acid-Schiff (PAS) pale
What is amorphous, eosinophilic, acellular material?
This hereditary amyloidosis subtype is caused by mutations in transthyretin, destabilizing its tetrameric structure and promoting fibril formation.
What is acute transthyretin (ATTR) (familial) amyloidosis?
The loss of this glomerular barrier property, due to amyloid infiltration, leads to the hallmark feature of nephrotic syndrome: massive proteinuria
What is increased glomerular permeability (charge loss)?
This protein, when mutated, is responsible for most hereditary forms of systemic amyloidosis with cardiac and neurologic involvement
What is transthyretin (TTR)
Unlike other causes of nephrotic syndrome, this blood pressure abnormality is uncommon in renal amyloidosis, even with advanced renal dysfunction
What is systemic hypertension?
Electron microscopy of renal amyloidosis demonstrates these randomly arranged structures, measuring 7–12 nm in diameter
What are non-branching amyloid fibrils?
This form of age-related amyloidosis involves deposition of wild-type transthyretin, often presenting with restrictive cardiomyopathy in older adults
What is wild-type transthyretin (ATTR) (senile systemic) amyloidosis?
In AA amyloidosis, chronic inflammation drives overproduction of this acute-phase reactant, which serves as the precursor for amyloid fibrils
What is serum amyloid A protein?
This FDA-approved therapy targets the underlying plasma cell clone in AL amyloidosis and is also used in multiple myeloma
What is daratumumab?
This physical sign, resulting from profound hypoalbuminemia, is a frequent presenting symptom in patients with nephrotic syndrome due to amyloidosis
What is peripheral edema?
Immunofluorescence in AL (light chain) amyloidosis often shows this pattern of staining for immunoglobulin light chains.
What is monoclonal (kappa or lambda) light chains?
This localized endocrine amyloidosis arises from amylin (islet amyloid polypeptide) accumulation and is associated with β-cell dysfunction
What is islet amyloidosis in type 2 diabetes mellitus?
The buildup of proteins in various organ systems (heart, liver, kidneys, etc).
What is amyloidosis?
Tubulointerstitial amyloid deposition can produce this concentrating defect, leading to polyuria and nocturia.
What is nephrogenic diabetes insipidus?
In renal amyloidosis, progression to this stage of kidney disease occurs in up to 30–40% of patients over the disease course
What is end-stage kidney disease (ESKD)?
In renal amyloidosis, immunofluorescence of the glomerulus may be characterized by this finding if there is no light chain deposition.
What is negative immunofluorescence?