Amyloidosis: Causes and Detection

Amyloidosis or deposition of amyloid in vital organs could be labeled as chronic pathological state. Amyloid is an abnormal protein derivative and amyloidosis is characterized by extracellular accumulation of this abnormal protein, which could be detected with Congo-Red staining during histological examination of biopsies/tissues. Genesis of amyloid is associated with B-cell (B Lymphocytes) and Plasma-cell disorders or chronic infections like tuberculosis. Renal (kidney) involvement in amyloidosis may affect all compartments of kidneys. Renal glomeruli, extraglomerular blood vessels, uriniferous tubules and even interstitium could be severely affected leading to impairment of renal function and can cause renal failure. Amyloid could be composed of one or more proteins out of around two dozen different monotypic polypeptides, including immunoglobulin light chains (AL type amyloid), immunoglobulin heavy chains (AH type amyloid), amyloid-A-protein (AA type amyloid), prealbumin, b-2 microglobulin, b-amyloid protein, islet amyloid polypeptide, procalcitonin, cystatin-C, apolipoprotein A-1 or A-2, gelsolin, lysozymes etc. Immunoglobulin light chains type (AL type) and amyloid-A-protein (AA type) amyloid mostly affect the kidneys. Almost all the patients with amyloidosis of kidneys have proteinuria (excretion of proteins in urine; >3g/day) and around 70% also have diminished renal function. On electron microscopy amyloid could be resolved as approximately 10 nm thick non branching and randomly arranged fibrils as illustrated in Figure-1.

Figure-1: Electron micrograph showing randomly arranged non-branching fibrils of amyloid in the mesangial area of a renal glomerulus. Original magnification 36000x.

Amyloid-A-protein type (AA type) amyloidosis is most often associated with chronic inflammatory diseases like tuberculosis, osteoarthritis, or rheumatoid arthritis. Some viral infections can also boost amyloidosis. Production of amyloidogenic light chains is associated with B-cell lymphoma, multiple myeloma or plasma-cell dyscrasia. AL and AA type amyloid have identical physicochemical properties. On renal biopsy evaluation we find acidophilic deposits which stain weakly with Periodic acid Schiff's stain or Silver stain. Amyloid stains bright red with Congo-Red stain and shows apple green birefringence by polarized light microscopy. Amyloid deposits could be revealed in the mesangium and peripheral capillary wall of renal glomerulus depending on the chronicity of the disease process. In advanced stages of amyloidosis, the amyloid deposits could be detected in arteries and interstitial tissue of kidneys in addition to glomeruli, by conventional methods and electron microscopy.

Kidney Diseases: Diagnostic Terms and Features

The genetic, environmental, chemical and biological factors are known to influence the bio-physiology and microanatomy of kidneys. A possible clinical diagnosis of kidney diseases or renal disorders could be achieved through ultrasonography, biochemical investigations of blood and urine analysis. The pathological diagnosis of non-neoplastic and neoplastic kidney diseases needs light microscopy (LM), immunofluorescence microscopy (IFM) and electron microscopy (EM) study of the kidney biopsy. Narrowing down at the appropriate and accurate diagnosis of a kidney disease needs expertise in the evaluation of LM, IFM and EM features. The light microcopy has its limitations in the exploration of microanatomy of renal lesions due to its low resolution power. The initial task in the pathological diagnosis of a kidney disease is to decide the renal compartments associated with the primary lesion or initial site of injury. The glomeruli, tubules, interstitium, extraglomerular vessels or podocytes may be affected primarily in various combinations in various renal diseases. The history of hypertension or diabetes in addition to chronic inflammatory disease like rheumatoid arthritis, osteomyelitis, tonsillitis and tuberculosis has its own implications in renal disorders. In some kidney diseases multiple components may be affected simultaneously by the pathogenic process. The glomeruli and blood vessels are found affected in certain forms of vasculitis. Immunological findings are mandatory to achieve an accurate diagnosis of vasculitis associated kidney diseases. Tubules and interstitium are found affected in tubulointerstitial nephritis. The role of EM and ultrastructural morphometry is implicit in achieving a diagnosis of thin basement membrane disease (TBMD), Alport's syndrome (hereditary nephropathy), minimal change disease (MCD), amyloidosis and evaluation of podocyte injury. The thickness and texture of glomerular basement membrane (GBM), reorganization of foot processes of podocytes and podocyte injury are directly associated with the biophysiology of proteinuria (excretion of protein in urine) and hematuria in some kidney diseases. The histopathologic lesions in the affected kidneys could only be explained with a thorough knowledge of universally accepted appropriate terms which could be understood by a clinician. The term focal is used when <50% of glomeruli are involved and the term diffuse refers to the involvement of 50% or more glomeruli. The term segmental is used when a part of a glomerular tuft is affected and the term global is used when entire glomerular tuft is affected. The term mesangial hypercellularity means >4 nuclei in the matrix of a peripheral mesangial segment. The term sclerosis refers to increased collagenous extracellular matrix causing mesangial expansion, obliterating capillary lumen or forming contact to Bowman's capsule. Some of the important diagnostic features of kidney biopsy evaluation have been cited below in a tabulated form: (For a full view of the Table - Just click on the image below)

The neoplastic kidney disease are renal cell carcinoma, juxta glomerular cell tumor, renal adenoma, oncocytoma and metastatic tumors which need immunohistochemical (IHC) and EM study for an accurate diagnosis.