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For further information, see CMDT Part 24-14: Nephrotic Spectrum Glomerular Diseases

KEY FEATURES

  • Proteinuria > 3 g/d

  • Hypoalbuminemia (serum albumin < 3.5 g/dL)

  • Peripheral edema

  • Hyperlipidemia

  • Oval fat bodies may be seen in the urine

  • Most common cause is diabetes; other causes include

    • Minimal change disease

    • Focal segmental glomerulosclerosis

    • Membranous nephropathy

    • Amyloidosis

CLINICAL FINDINGS

  • Patient may be asymptomatic

  • Nephrotic syndrome

    • Peripheral edema likely due to hypoalbuminemia and sodium retention

    • Edema can become generalized

    • Dyspnea caused by pulmonary edema, pleural effusions, and diaphragmatic compromise with ascites

DIAGNOSIS

  • Urinalysis: proteinuria; few cellular elements or casts

    • Oval fat bodies can occur in marked hyperlipidemia

    • Appear as "grape clusters" under light microscopy and "Maltese crosses" under polarized light

  • Serum albumin < 3 g/dL, serum protein < 6 g/dL

  • Hyperlipidemia occurs in > 50% of patients with nephrotic syndrome and worsens with the severity of the nephrotic syndrome

  • Elevated erythrocyte sedimentation rate

  • Deficiencies of vitamin D, zinc, and copper if heavy urinary excretion of binding proteins

  • The following tests may help elucidate the underlying cause of glomerular disease

    • Complement levels

    • Serum and urine protein electrophoresis and immunofixations

    • Serum free light chains

    • Antinuclear antibodies

    • Phospholipase A2 receptor (PLA2R) antibody titers

    • HbA1c

    • Serologic testing for hepatitis B and C, HIV, and syphilis

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

TREATMENT

Proteinuria

  • In those with isolated proteinuria, dietary protein restriction may be helpful in slowing progression of kidney disease

  • Anti-proteinuric therapy slows progression of kidney disease for patients with and without diabetes

    • Angiotensin-converting enzyme (ACE) inhibitors

    • Angiotensin receptor blockers (ARB)

    • Mineralocorticoid receptor antagonists

    • Sodium-glucose cotransporter-2 (SGLT2) inhibitors

    • Can be used in patients with reduced GFR if, after initiation of therapy or after dose titration,

      • Significant hyperkalemia (potassium > 5.5 mEq/L) does not occur

      • Serum creatinine rises < 30%

      • Patients are counseled on preventive practices to avoid acute kidney injury and hyperkalemia

    • Combination ARB and ACE inhibitor therapy is not recommended

    • Magnetic resonance angiography is not recommended when eGFR is less than 30 mL/min

Edema

  • Sodium restriction

  • Most patients also require diuretic therapy

  • Loop and thiazide diuretics in combination

Hyperlipidemia

  • Dietary modification and exercise

  • Pharmacologic treatment is usually required

Hypercoagulable state

  • In patients with thrombosis, warfarin for at least 3–6 months

  • Indefinite anticoagulation may be required for

    • Renal vein thrombosis

    • Pulmonary embolus

    • Recurrent thromboemboli

    • Ongoing nephrotic syndrome that poses a risk of thrombosis recurrence

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