Nephrotic syndrome differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Differentiating Nephrotic Syndrome from other Diseases

The differential diagnosis of nephrotic syndrome includes other disease with similar findings on physical examination, such as lower extremity edema, or similar clinical findings, such as hypoalbuminemia

Common Differential Diagnoses of Nephrotic Syndrome

Differential Diagnosis	Characteristic Features
Congestive Heart Failure	History of cardiovascular disease Dyspnea, orthopnea, paroxysmal nocturnal dyspnea, pitting edema, pulmonary edema Low ejection fraction on echocardiography Elevated brain natriuretic peptide (BNP) levels Abnormal heart rate Third heart sound Lung crackles or wheezing Elevated jugular venous pressure Cardiomegaly with cardiothoracic ratio on xray > 0.5
Liver Cirrhosis	Gynecomastia, spider angiomata, testicular atrophy, encephalopathy Pitting edema and ascites Normal/elevated liver transaminases Prolonged INR Hypoalbuminemia Shrunken liver on imaging
Protein Losing Enteropathy	Watery diarrhea Abdominal pain Weight loss Hypoalbuminemia and hypoglobulinemia Stool alpha-1-antitrypsin Imaging and endoscopy findings depend on etiology of enteropathy
Malignancy	Weight loss, fever, fatigue Pitting or non-pitting edema, ascites, pleural effusion, pulmonary edema Lymphatic obstruction
Lymphedema	History of lymph node resection and/or radiation therapy, especially in breast cancer Fatigue Swollen limb with localized fluid accumulation Skin discoloration
Venous Insufficiency	Painful extremities Bluish Skin discoloration Edema mostly after prolonged standing Stasis dermatitis

^{Adapted from Hull RP, Goldsmith DJ. Nephrotic syndrome in adults. BMJ. 2008; 336:1185-9}

• Heart failure: The patient is older, with a history of heart disease. Jugular venous pressure is elevated on examination, might hear heart murmurs. An echocardiogram is the gold standard investigation

• Liver failure: History suggestive of hepatitis/ cirrhosis: alcoholic, IV drug user, some hereditary causes. Stigmata of liver disease are seen: dilated veins over umbilicus (caput medusae), scratch marks, enlarged spleen, spider angiomata, encephalopathy, bruising, nodular liver

• Acute fluid overload in someone with kidney failure: These people are known to have kidney failure, and have either drunk too much or missed their dialysis.

• Metastatic cancer: When cancer seeds the lungs or abdomen it causes effusions and fluid accumulation due to obstruction of lymphatics and veins as well as serous exudation.