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Glomerulonephropathies are disorders that primarily affect the structure and function of the renal glomerular apparatus. Frequently encountered in clinical practice, glomerulopathies are usually suspected from the history and the urinary findings of hematuria, red cell casts, or proteinuria. The many different causes of glomerular disease can be generally classified into one of three major syndromes: Nephrotic syndrome, nephritic syndrome, and asymptomatic renal disease. However, there may be considerable overlap in their clinical presentation with some diseases presenting with components of both syndromes.

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Essentials of Diagnosis

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  • Proteinuria >3.5 g/1.73 m2/24 hours (40–50 mg/kg/day).
  • Hypoalbuminemia.
  • Edema.
  • Hyperlipidemia.
  • Lipiduria.

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General Considerations

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Nephrotic syndrome may appear as a primary (idiopathic) renal disease or occur in association with any of a number of systemic conditions and hereditary diseases. The most common primary glomerular diseases include membranous nephropathy, focal segmental glomerular sclerosis, minimal change, and membranoproliferative glomerulonephritis (MPGN). In the United States, diabetes mellitus is the most common cause of nephrotic syndrome. Approximately one-third of patients with both type 1 and type 2 diabetes mellitus of at least a 25-year duration will develop nephrotic syndrome, predictably leading to renal failure. Other systemic diseases that may lead to the nephrotic syndrome include systemic lupus erythematous (SLE), amyloidosis, and leukemia.

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Pathogenesis

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Nephrotic syndrome generally reflects noninflammatory damage to the glomerular capillary wall. The underlying glomerular disease results in proteinuria, which occurs from alterations in the charge or size selectivity of the glomerular capillary wall. This increases glomerular permeability to plasma proteins. Albumin is the principal urinary protein lost, but other plasma proteins lost in the urine include hormone-carrying proteins such as vitamin D-binding protein, transferrin, and clotting inhibitors.

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Prevention

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We do not know how to prevent primary nephrotic syndrome. Secondary nephrotic syndromes can often be improved and sometimes completely reversed by treating and controlling the underlying disease.

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Clinical Findings

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Symptoms and Signs

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Nephrotic syndrome can present with a spectrum of findings ranging from asymptomatic proteinuria to the most common presentation of edema. Edema occurs initially in areas of high intravascular hydrostatic pressure such as in the feet and ankles as well as in areas in which tissue hydrostatic pressure is lowest such as the periorbital and scrotal areas. If the edema is severe and generalized it can present as anasarca.

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Laboratory Findings

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Urinalysis
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Urine dipstick often demonstrates 3+ to 4+ protein and 24-hour urine collection with >3.5 g protein/1.73 m2. Proteinuria can also be estimated from a single urine specimen by calculating the ratio of total urine protein in mg/dL to urine creatinine in mg/dL. This ratio approximates the actual 24-hour protein excretion in grams per day per 1.73 m2 body surface area. Typically the urine sediment has few cells ...

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