NEPHROTIC SYNDROME
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.
| SYSTEMIC CAUSES | GLOMERULAR DISEASE | 
|---|---|
| Diabetes mellitus, SLE, amyloidosis, HIV-associated nephropathy | Membranous Minimal change disease  | 
| Drugs: gold, penicillamine, probenecid, street heroin, NSAIDs, pamidronate, interferons | Focal glomerulosclerosis | 
| Infections: bacterial endocarditis, hepatitis B, shunt infections, syphilis, malaria, hepatic schistosomiasis | Membranoproliferative 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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Citation
Kasper, Dennis L., et al., editors. "NEPHROTIC SYNDROME." Harrison's Manual of Medicine, 20th ed., McGraw Hill Inc., 2020. harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623721/all/NEPHROTIC_SYNDROME. 
NEPHROTIC SYNDROME. In: Kasper DLD, Fauci ASA, Hauser SLS, et al, eds. Harrison's Manual of Medicine. McGraw Hill Inc.; 2020. https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623721/all/NEPHROTIC_SYNDROME. Accessed November 3, 2025.
NEPHROTIC SYNDROME. (2020). In Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.), Harrison's Manual of Medicine (20th ed.). McGraw Hill Inc.. https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623721/all/NEPHROTIC_SYNDROME
NEPHROTIC SYNDROME [Internet]. In: Kasper DLD, Fauci ASA, Hauser SLS, Longo DLD, Jameson JLJ, Loscalzo JJ, editors. Harrison's Manual of Medicine. McGraw Hill Inc.; 2020. [cited 2025 November 03]. Available from: https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623721/all/NEPHROTIC_SYNDROME.
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