Characterized by albuminuria (>3.5 g/d) and hypoalbuminemia (<30 g/L) and accompanied by edema, hyperlipidemia, and lipiduria. Protein excretion should be quantified by 24-h urine collection, but can be monitored by measurement of the urine protein:creatinine ratio or albumin:creatinine ratio on a random spot urine. The measurement of creatinine excretion helps define the adequacy of 24-h urine collections: daily creatinine excretion should be 20–25 mg/kg lean body weight in men and 15–20 mg/kg lean body weight in women. For random urine samples, the ratio of protein or albumin to creatinine in mg/dL approximates the 24-h urine protein excretion, since creatinine excretion is only slightly >1000 mg/d per 1.73 m2. A urine protein:creatinine ratio of 5 is thus consistent with 5 g/d per 1.73 m2. Quantification of urine protein excretion on spot urines has largely supplanted formal 24-h urine collections for monitoring or screening, due to the greater ease and the need to verify a complete 24-h collection. The total protein:creatinine ratio does not detect microalbuminuria, a level of albumin excretion that is below the level of detection by tests for total protein; urine albumin:creatinine measurement is therefore preferred as a screening tool for lesser proteinuria.

In addition to edema, the complications of NS can include renal vein thrombosis and other thromboembolic events, infection, vitamin D deficiency, protein malnutrition, and drug toxicities due to decreased protein binding.

In adults, the most common cause of NS is diabetes. A minority of cases are secondary to SLE, amyloidosis, drugs, neoplasia, or other disorders (Table 145-3). By exclusion, the remainder are idiopathic. With the exception of diabetic nephropathy, suggested by a compatible natural history of proteinuria in a diabetic pt, a renal biopsy is required to make the diagnosis and determine therapy in NS.

TABLE 145-3: Causes of Nephrotic Syndrome (NS)
Diabetes mellitus, SLE, amyloidosis, HIV-associated nephropathy


Minimal change disease

Drugs: gold, penicillamine, probenecid, street heroin, NSAIDs, pamidronate, interferonsFocal glomerulosclerosis
Infections: bacterial endocarditis, hepatitis B, shunt infections, syphilis, malaria, hepatic schistosomiasisMembranoproliferative GN
Malignancy: multiple myeloma, light chain deposition disease, Hodgkin’s and other lymphomas, leukemia, carcinoma of breast and GI tract

Mesangioproliferative GN

Immunotactoid and fibrillary GN

Abbreviation: GN, glomerulonephritis.
Source: Glassock RJ, Brenner BM: Harrison’s Principles of Internal Medicine, 13th ed, 1995.

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