Nephrotic Syndrome

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

Diagnosis

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 ...