Treatment

• Management of symptoms and complications

• Disease-specific measures

• Dietary sodium restriction: < 3 g/day (usually 1.5–2 g/day)

• Fluid restriction: < 1.5 liters/day

• Diuretic therapy

  • Approach

    • Target weight loss: 0.5–2 kg per day (avoid over-aggressive diuresis)

    • High diuretic doses often required because of diuretic resistance

    • Monitor serum electrolytes and renal function.

  • Options

    • First-line: oral loop diuretic (e.g., furosemide, bumetanide, torsemide)

    • Second-line:

      • Add oral thiazide or thiazide-like diuretic (e.g., metolazone)

      • AND/OR switch to IV loop diuretic (e.g., IV furosemide)

    • Consider adjunctive IV albumin30–60 minutes prior to intravenous loop diuretic.

Elimination or reduction of proteinuria is a major treatment goal for nephrotic syndrome and can lead to increased serum albumin, decreased edema, attenuation of the metabolic effects of heavy proteinuria (e.g., hyperlipidemia), reduction in risk of thromboembolism and infection, and slowing of the progression of chronic kidney disease.

• Antiproteinuric therapy

  • Indicated in most patients

  • RAAS inhibitor: ACEI (e.g., ramipril) or ARB (e.g., losartan) are commonly used

    • Effects

      • Reduces proteinuria

      • Treats hypertension

      • May slow progression of any underlying renal disease (e.g., diabetic nephropathy)

    • Avoid in patients with AKI, hyperkalemia, or abrupt onset of nephrotic syndrome.

    • Monitoring: blood pressure, serum potassium, and renal function

  • Other measures that may be beneficial in combination with an ACEI or ARB:

    • Low sodium diet (e.g., dietary sodium restriction to ∼ 1.2 g/day)

    • Thiazide diuretic (e.g., hydrochlorothiazide)

    • Mineralocorticoid receptor antagonist (e.g., spironolactone)

  • Dietary protein: avoid very high-protein diet but ensure adequate protein intake (0.8–1.0 g/kg daily).

• Lipid-lowering therapy (e.g., atorvastatin)

• Indications similar to those in other patients with a high risk of cardiovascular disease

• Prophylactic anticoagulation

• Therapeutic anticoagulation

• Serum albumin level: Prophylaxis is usually considered when serum albumin is < 2–2.5 g/dL.

• Histological diagnosis: VTE risk is higher in primary membranous nephropathy

• Coexistence of other risk factors for thromboembolism

  • Immobility due to edema, obesity, malignancy, intercurrent illness, or hospital admission

  • Coexisting prothrombotic tendency or thrombophilic state

  • Previous history of thromboembolic events

  • Proteinuria > 10 g/day

  • Body mass index > 35 kg/m2

  • Recent abdominal or orthopedic surgery

  • New York Heart Association class III to IV congestive heart failure

• Risk of bleeding: Avoid prophylactic anticoagulation in patients at high risk of bleeding (e.g., HAS-BLED score ≥ 3).

• Options

  • Unfractionated heparin

  • Low molecular weight heparin (e.g., enoxaparin)

  • Oral warfarin (target INR 2.0–3.0)

  • Evidence for direct oral anticoagulants (DOACs) is lacking; consider only in patients who are unable to tolerate unfractionated heparin, low molecular weight heparin, or warfarin

• Duration: until serum albumin is > 3.0 g/dL

• Indications: arterial thrombosis, venous thrombosis, pulmonary embolism

• Options

  • Low molecular weight heparin (e.g., enoxaparin)

  • Oral warfarin (target INR 2.0–3.0

  • DOACs may be carefully considered as alternative agents but evidence supporting their use is limited

Consider screening for hepatitis B, HIV, latent TB, strongyloides, and/or syphilis based on geography, exposure history, and risk factors

• Pneumococcal vaccination

• Annual vaccination for influenza

• Consider monthly IV immunoglobulin in patients with repeated bacterial infections and serum IgG < 600 mg/dL

• Consider pneumocystis pneumonia prophylaxis (e.g., trimethoprim-sulfamethoxazole) in patients receiving high-dose steroids and/or other immunosuppressive therapy

often treated with immunosuppressive therapy

• Immunosuppressive therapies may include:

  • Glucocorticoids (often used initially)

  • Additional immunosuppressants (e.g., cyclophosphamide, calcineurin inhibitors) in patients with steroid-resistant nephrotic syndrome or severe disease

• Management in adults is usually guided by biopsy-based histological diagnosis.

• Children are often treated initially with empiric corticosteroids for presumed minimal change disease

Treat the underlying cause

• Initial management: conservative therapy including an RAAS inhibitor (i.e., ACEI or ARB)

• Consider immunosuppressive therapy for severe or refractory disease.

  • Prednisone AND cyclophosphamide

  • Alternatives: cyclosporine, tacrolimus, OR rituximab

• Initial management: supportive therapy including an RAAS inhibitor (i.e., ACEI or ARB).

• Consider immunosuppressive therapy for all patients with nephrotic syndrome due to FSGS.

  • Prednisone

  • Alternative: calcineurin inhibitor (cyclosporin OR tacrolimus)

• Initial management: immunosuppressive therapy

  • Prednisone

  • Alternative: cyclophosphamide OR calcineurin inhibitor

• Strict glycemic control

• RAAS inhibition (e.g., ACEI or ARB)

• Optimization of blood pressure control

• Close surveillance and timely referral to renal replacement therapy if ESRD is anticipated

• Treatment of the underlying disease

  • AL amyloidosis: treatment of multiple myeloma or other plasma cell dyscrasia

  • AA amyloidosis: treatment of underlying inflammatory condition