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Patients with nephrotic syndrome classically have edema (often periorbital), hypertension, hypoalbuminemia, hyperlipidemia, and at least 3.5 g/24 hour of proteinuria.


  1. Etiology

    1. Primary glomerular diseases

      1. Etiology uncertain but probably immune mediated

      2. Most common pathologies found in adults are membranous and focal segmental glomerulosclerosis (33% each), with membranous being more common in white patients and focal segmental glomerulosclerosis more common in black patients.

      3. Less common pathologies found in adults are minimal change disease (15%) and membranoproliferative glomerular disease (including IgA nephropathy) (14%).

      4. In patients over age 65 who undergo kidney biopsy (recognizing that many patients with presumed diabetic nephropathy do not have a biopsy), approximately 15% have minimal change disease, 30–40% have membranous nephropathy, and 10–12% have amyloidosis.

    2. Secondary glomerular disease

      1. Diabetes is the most common cause in the United States.

      2. Systemic lupus erythematosus generally causes an inflammatory nephritis, but sometimes causes a noninflammatory, membranous pathology.

      3. Amyloidosis and plasma cell myeloma (formerly multiple myeloma) should be considered in patients over age 40.

      4. Infections commonly associated with nephrotic syndrome include HIV, hepatitis B, hepatitis C, syphilis, and malaria.

      5. Malignancies, especially lung, breast, prostate, and colon cancer as well as Hodgkin lymphoma are associated with nephrotic syndrome.

        1. 5–25% of patients with membranous nephropathy have a malignancy, with the association being strongest for patients over 60 years old.

        2. The cancer may be diagnosed at the same time as the kidney disease but often is found later.

      6. Many drugs, including NSAIDs, captopril, tamoxifen, lithium, and heroin, can cause nephrotic syndrome.

  2. Clinical consequences

    1. Primary sodium retention by the kidney, related to low effective circulating volume, causes edema and hypertension.

    2. Albumin excretion leads to hypoalbuminemia, which also contributes to edema formation.

    3. Alterations in lipoprotein production and catabolism lead to elevations of low-density lipoprotein and sometimes triglycerides.

    4. Immunoglobulin excretion and depression of T cell function causes increased susceptibility to infection.

    5. Thromboembolic complications

      1. Due to increased procoagulatory factors and fibrinogen, altered fibrinolytic system, urinary loss of antithrombin III, and increased platelet activity

      2. Relative risk of DVT is 1.7 with an annual incidence of 1.5%; the annual incidence of renal vein thrombosis is 0.5%.

      3. Relative risk of pulmonary embolism is 1.4 but is 6.8 for patients aged 18–39 years.

      4. Risk factors for venous thromboembolism include serum albumin < 2.0–2.5 g/dL, protein excretion > 8 g/24 h, and being within 6 months of diagnosis of nephrotic syndrome.

      5. The role of prophylactic anticoagulation is unclear but should be considered in high-risk patients.

      6. Arterial thrombosis is rare.


  1. Nephrotic syndrome is defined by the presence of urinary protein excretion of at least 3.5 g/24 hours, measured with either a 24-hour specimen or a spot albumin/creatinine ratio > 3000–3500 mcg/mg.

  2. Laboratory evaluation should include

    1. CBC

    2. Comprehensive metabolic panel (kidney and liver function, including serum albumin)

    3. PT/INR, PTT

    4. Fasting glucose and HbA1c

    5. Antinuclear antibody

    6. HIV

    7. Hepatitis B serology (surface antigen, core antibody)

    8. Hepatitis C antibody

    9. Serum and urine ...

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