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For further information, see CMDT Part 22-15: Nephrotic Spectrum Glomerular Diseases

Key Features

Essentials of Diagnosis

  • Bland urine sediment (few if any cells or cellular casts)

  • Nephrotic syndrome manifestations:

    • Heavy proteinuria (urine protein excretion > 3 g per 24 hours)

    • Hypoalbuminemia (albumin < 3 g/dL)

    • Peripheral edema

    • Hyperlipidemia

    • Oval fat bodies may be seen in the urine

General Considerations

  • Causes

    • Diabetes mellitus (most common)

    • Minimal change disease

    • FSGS

    • Membranous nephropathy

    • Amyloidosis

  • Any of these entities can present on the less severe end of the nephrotic spectrum with a bland urinalysis and proteinuria, or with the most severe presentation of the nephrotic syndrome

  • Serum creatinine may be abnormal at the time of presentation, depending on the severity and acuity of the disease

Clinical Findings

  • Patients with subnephrotic range proteinuria do not manifest symptoms of the kidney disease

  • In those with the nephrotic syndrome, peripheral edema is present and is most likely due to sodium retention and hypoalbuminemia-induced low plasma oncotic pressure

  • Edema

    • May develop solely in dependent regions, such as the lower extremities

    • May become generalized and include periorbital edema

  • Dyspnea due to pulmonary edema, pleural effusions can occur

  • Diaphragmatic compromise due to ascites can also occur


Laboratory Findings

  • Urinalysis

    • Urinary dipstick is a good screening test for proteinuria; however, it detects only albumin

    • A spot urine protein to urine creatinine ratio ([Uprotein]/[Ucreatinine]) gives a reasonable approximation of grams of protein excreted per day (ratio < 0.2 is normal and corresponds to excretion of < 200 mg/24 hours); a 24-hour urine sample for protein excretion is rarely needed

    • Microscopically, the urinary sediment has relatively few cellular elements or casts

    • However, if marked hyperlipidemia is present, urinary oval fat bodies may be seen

      • Appear as "grape clusters" under light microscopy

      • Appear as "Maltese crosses" under polarized light

  • Blood chemistries

    • Hypoalbuminemia (< 3 g/dL [30 g/L])

    • Hypoproteinemia (< 6 g/dL [60 g/L])

    • Hyperlipidemia

      • Occurs in over 50% of patients with early nephrotic syndrome

      • Becomes more frequent and worsens in degree as the severity of the nephrotic syndrome increases

    • Patients may become deficient in vitamin D, zinc, and copper from loss of binding proteins in the urine

    • Laboratory testing to determine the underlying cause may include

      • Complement levels

      • Serum and urine protein electrophoresis

      • Serum free light chains

      • Antinuclear antibodies

      • PLA2R antibody titers

      • Serologic tests for viral hepatitides

Diagnostic Procedures

  • Kidney biopsy

    • Often performed in adults with new-onset idiopathic nephrotic syndrome if a primary renal disease that may require immunosuppressive therapy is suspected

    • Chronically and significantly decreased GFR indicates irreversible kidney disease mitigating the usefulness of kidney biopsy

    • In the setting of long-standing diabetes mellitus type 1 or 2, proteinuric renal disease is rarely biopsied unless

      • Atypical features (such as ...

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