Proteinuria, nephrotic syndrome

Rare reactions with long-term use include peptic ulcer disease, GI bleeding, gastritis, a severe hepatic reaction (cholestasis, jaundice), nephrotoxicity (dysuria, hematuria, proteinuria, nephrotic syndrome), and a severe hypersensitivity reaction (particularly in patients with systemic lupus erythematosus or other collagen diseases). 

Nephrotoxicity (dysuria, hematuria, proteinuria, nephrotic syndrome) and severe hypersensitivity reaction (fever, chills, bronchospasm) occur rarely. 

Proteinuria, nephrotic syndrome, and various forms of renal lesions can be caused or exacerbated by interferon alfa (SED-14,1252). 

These studies led to the realization that proteinuria— the abnormal appearance of protein in the urine— could result not only from the enlargement of submicroscopic holes in the glomerular capillary wall, but also from the loss or neutralization of its negatively charged components. This finding has provided a new direction for research on the molecular basis for the nephrotic syndrome, a group of kidney diseases all characterized by massive proteinuria. 

In an extensive study (A4) of 88 Nigerian children with the nephrotic syndrome, 80% were observed with a nonselectivity proteinuria, and steroid therapy was ineffective in most of these ehildren. Unlike European and American children with the nephrotic syndrome, less than half of the Nigerian children who had highly selective type proteinuria showed... 

In all forms of glomerular nephritis in tropical populations in Africa, there was increased protein in the urine. In the selective proteinuria of the nephrotic syndrome most of the protein was mainly albumin and transferrin, with lower concentrations of IgG and other globulins. On the other hand, the urine of the nonselective proteinuria of the nephrotic syndrome is characterized by much higher concentrations of IgG, IgA, a2-macroglobulins, and some IgM. Differential protein clearance to establish selectivity of proteinuria has been discussed above. 

Edematous states To induce diuresis or remission of proteinuria in the nephrotic syndrome (without uremia) of the idiopathic type or that caused by lupus erythematosus. 

Proteinuria Total urinary proteins more than 1 g/day were seen in 0.7% of captopril patients. Nephrotic syndrome occurred in approximately 20% of these cases. Hypotension ... 

Renal function impairment Proteinuria and hematuria may develop and may be a warning sign of membranous glomerulopathy, which can progress to a nephrotic syndrome. 

Renal effects Acute renal insufficiency, interstitial nephritis with hematuria, nephrotic syndrome, proteinuria, hyperkalemia, hyponatremia, renal papillary necrosis, and other renal medullary changes may occur. 

This syndrome is characterized by proteinuria >3.5 g/day, hypoalbuminuria <3 g/dl, hyperlip-idaemia with an elevation of serum cholesterol, edema and oval fat bodies and fatty casts in the urinary sediment. A variety of disorders may produce nephrotic syndrome but, in the majority of cases, no cause is found. It is appropriate to define the selection of studies from the history and physical examination. Tests to order are antinuclear antibody, rheumatoid factor, cryoglobulins, serum complement, HBsAg VDRL serology (syphilis), protein electrophoresis of the serum and urine and HIV. If the cause is unclear a renal biopsy is done to define the glomerular lesion as treatment may on the underlying glomerular lesion. 

Hypercholesterolaemia and hypertriglyceridaemia commonly occur in patients with severe proteinuria. It may be associated with a higher incidence of cardiovascular disease. Dietary treatment is of limited value if the underlying cause of the nephrotic syndrome is not successfully controlled. Statins should be considered to lower the serum cholesterol. 

Nephrotic syndrome is characterized by proteinuria and edema due to some form of glomerulonephritis. The resulting fall in plasma protein concentration decreases vascular volume, which leads to diminished renal blood flow. This in turn causes secondary aldosteronism characterized by Na and water retention and K+ depletion. Rigid control of dietary Na is essential. Therapy of the nephrotic syndrome using a thiazide (possibly with a K -sparing diuretic) to control the secondary aldosteronism, is a useful initial approach to treatment Since nephrotic edema is frequently more difficult to control than cardiac edema, it may be necessary to switch to a loop diuretic (and spironolactone) to obtain adequate diuresis. 

Signs and symptoms of gold toxicity, the primary serious reaction, include decreased Hgb level, decreased granulocyte count (less than 150,000/mm ), proteinuria, hematuria, stomatitis, blood dyscrasias (anemia, leukopenia WBC count less than 4000/mm, thrombocytopenia, and eosinophilia), glomerulonephritis, nephrotic syndrome, and cholestatic jaundice. 

The nephrotic syndrome, characterized clinically by proteinuria, is a rare and idiosyncratic reaction to lithium. As with other uncommon adverse effects, the issue of causation versus coincidence must be considered. Treatment includes cessation of the drug and, when necessary, corticosteroids such as prednisone ( 322). 

Prednisolone can cause an abrupt rise in proteinuria in patients with nephrotic syndrome. A placebo-controlled study in 26 patients aged 18-68 years with nephrotic syndrome has clarified the mechanisms responsible for this (163). Systemic and renal hemodynamics and urinary protein excretion were measured after prednisolone (125 mg or 150 mg when body weight exceeded 75 kg) and after placebo. Prednisolone increased proteinuria by changing the size-selective barrier of the glomerular capillaries. Neither the renin-angiotensin axis nor prostaglandins were involved in these effects of prednisolone on proteinuria. 

Pathogenesis of Proteinuria in Acquired Forms of Nephrotic Syndrome... 185... 

Nephrotic syndrome is a clinical and laboratory syndrome defined by heavy proteinuria (exceeding 3.5 g/1.73 m2 of body surface area in adults, or 40 mg/hr/m2 in children), accompanied by hypoproteinemia (mainly hypoalbuminemia), hypercholesterolemia (in severe cases also hypertriacylglycerolemia), lipiduria, and edema. 

Congenital nephrotic syndrome of the Finnish type is clinically characterized by heavy proteinuria present already in utero, which leads without nephrectomy and renal replacement therapy to the death of the affected children usually before the second year of life. Electronoptically, the glomerular basement membrane seems to be intact with the fusion of the podocyte foot processes. The chemical composition of the glomerular basement membrane is normal in patients with congenital nephrotic syndrome and all genes of the main proteins of the glomerular... 

Familial forms of nephrotic syndrome are very rare, but they are very important for the elucidation of the molecular pathogenesis of proteinuria in the far more common acquired glomerular diseases accompanied by nephrotic syndrome. 

Nephrotic syndrome may complicate the course of many primary and secondary glomerulopathies. Diabetic nephropathy is the most common cause of nephrotic proteinuria (not always accompanied by full-blown nephrotic syndrome). Lupus nephritis and renal amyloidosis are much rarer secondary glomerulopathies resulting in nephrotic syndrome. The prevalence of primary glomerulopathies differs between Blacks and Whites (focal segmental glomerulosclerosis is more common... 

Minimal change disease is the most common cause of nephrotic syndrome in children, presenting typically with rapid onset of mostly steroid-sensitive nephrotic syndrome, usually with selective proteinuria (albuminuria). Light-microscopic morphology of the kidney is normal and immunofluorescence is negative. Foot process effacement on electron microscopy is the only observed pathology. 

---