Nephrotic Syndrome and its Serious Effects

Urine examination shows critical abnormalities in nephrotic syndrome. The urine may froth if passed in a container or if shaken in a test tube. The dipstick test always shows extensive excretion of protein in urine. Total excretion of protein per day should be measured in 24-hour's collection of urine. The nephrotic syndrome is the consequence of prolonged massive proteinuria (excretion of protein in urine). The proteinuria exceeds 3.5 g/24-hours in adults or 50 mg/kg body-weight in children. Nephrotic syndrome is characterized by proteinuria, hematuria (blood in urine), hypertension (high blood pressure), oliguria (low output of urine per day), edema (swelling: apparently suborbital puffy eyes) and diminished renal function. Urine may be brown or red. Sodium (Na⁺) retention, increased circulating blood volume and hypertension (high blood pressure) may lead to cardiomegaly (enlargement of heart). Nephrotic syndrome is usually characterized by insidious onset of massive edema, proteinuria, hypoalbuminemia (low level of albumin in blood) and hyperlipidemia (high level of cholesterol in blood). There could be massive retention of sodium (Na⁺) and a tendency to excessive potassium (K⁺) loss. Serious ill effect of the nephrotic syndrome could be a tendency towards hypercoagulability (blood clotting disorder) which may lead to venous or arterial thrombosis and embolism. Susceptibility to chest (lung) infections may increase due to decreased immunoglobulins' level in blood. Serum calcium (Ca⁺⁺) level could be low as this is related to the level of albumin in blood. Dysfunction of proximal tubules of kidneys may cause glycosuria (excretion of glucose/sugar in urine) or aminoaciduria.

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.