What is the typical management of nephritic and nephrotic syndrome?

Management of Nephritic and Nephrotic Syndrome

The management of nephritic and nephrotic syndrome requires targeted immunosuppressive therapy combined with supportive care, with specific regimens determined by the underlying etiology, disease severity, and patient-specific factors. 1

Clinical Presentation and Diagnosis

Nephrotic Syndrome

• Definition: Characterized by proteinuria >3.5g/24h, hypoalbuminemia (<3.0 g/dL), edema, and hyperlipidemia 2, 3
• Common presentations:
  • Periorbital edema (most noticeable in morning)
  • Dependent pitting edema (more common later in day)
  • Hyperlipidemia
  • Increased risk of thromboembolism and infections

Nephritic Syndrome

• Definition: Characterized by hematuria, proteinuria, hypertension, and possibly acute kidney injury 4, 5
• Common presentations:
  • Hematuria (microscopic or gross)
  • Hypertension
  • Fluid retention
  • Abnormal kidney function

Diagnostic Workup

• Quantitative proteinuria measurement (PCR >300-350 mg/mmol indicates nephrotic range) 2
• Serum albumin, lipid profile, renal function tests
• Immunological and infectious evaluations
• Kidney biopsy (indicated in adults with nephrotic syndrome without clear etiology, atypical presentations, rapidly progressive glomerulonephritis) 1
• Genetic testing (first-line in suspected atypical cases, especially congenital/infantile forms) 1

Management of Nephrotic Syndrome

General Supportive Measures

1. Anti-proteinuric therapy:

   • ACE inhibitors or ARBs for all patients with UPCR >500 mg/g or hypertension 6
   • Dose titrated based on proteinuria response rather than preset blood pressure goals 1

2. Management of edema:

   • Diuretics (furosemide 0.5-2 mg/kg per dose) 1
   • Avoid intravenous fluids and saline when possible 6
   • Albumin infusions based on clinical indicators of hypovolaemia (oliguria, acute kidney injury, prolonged capillary refill time, tachycardia, hypotension), not serum albumin levels 6

3. Hyperlipidemia management:

   • Statins recommended for persistent dyslipidemia 6, 1
   • Target LDL-cholesterol 2.58 mmol/litre (100 mg/dl) 6

4. Thrombosis prevention:

   • Consider anticoagulant treatment in nephrotic syndrome with serum albumin <20 g/L 6
   • Especially important if persistent or with anti-phospholipid antibodies 6

Disease-Specific Treatment

Lupus Nephritis

1. Initial treatment for proliferative LN (Class III/IV):

   • Mycophenolate mofetil (target dose 3g/day) or cyclophosphamide, plus
   • Glucocorticoids (initially 0.5-1.0 mg/kg/day, tapering to ≤10 mg/day by 4-6 months) 6

2. Pure Class V (membranous) LN with nephrotic-range proteinuria:

   • MMF (target dose 3g/day for 6 months) with oral prednisone (0.5 mg/kg/day) 6
   • Alternatives: cyclophosphamide, calcineurin inhibitors, or rituximab 6

3. Maintenance therapy:

   • MMF at lower doses (2g/day) or azathioprine (2 mg/kg/day) for at least 3 years 6
   • Low-dose prednisone (2.5-5 mg/day) 6
   • Hydroxychloroquine to reduce renal flares 6

4. Refractory disease:

   • Switch from MMF to cyclophosphamide or vice versa
   • Consider rituximab (1000 mg on days 0 and 14) 6
   • Belimumab may be considered as add-on treatment 6

Focal Segmental Glomerulosclerosis (FSGS)

• Prednisone/prednisolone at 1 mg/kg/day for 4-16 weeks or until complete remission 1
• For steroid-resistant cases: calcineurin inhibitors (cyclosporine, tacrolimus) 6, 1
• Alternative options: mycophenolate mofetil with high-dose dexamethasone 6

Congenital Nephrotic Syndrome

• Focus on supportive care rather than immunosuppression 6, 1
• Consider nephrectomy in patients with persistent hypovolaemia, thrombosis, and failure to thrive 6
• Early referral to transplant unit 6

Management of Nephritic Syndrome

Common Causes and Specific Management

• Post-infectious glomerulonephritis: Antimicrobial therapy for underlying infection
• IgA nephropathy: ACE inhibitors/ARBs, consider corticosteroids for persistent proteinuria
• Lupus nephritis: As outlined above
• ANCA-associated vasculitis: Cyclophosphamide or rituximab plus corticosteroids

Monitoring and Follow-up

1. Regular monitoring:

   • Visits every 2-4 weeks during first 2-4 months after diagnosis or flare 6
   • At each visit: body weight, blood pressure, eGFR, serum albumin, proteinuria, urinary sediment 6
   • For lupus nephritis: also monitor serum C3/C4, anti-dsDNA antibodies 6

2. Response assessment:

   • Complete response: return of serum creatinine to baseline and decline in UPCR to <500-700 mg/g
   • Partial response: stabilization or improvement of serum creatinine but UPCR still >500-700 mg/g

3. Consider repeat kidney biopsy in cases of:

   • Worsening kidney function
   • Non-responsiveness to treatment
   • Relapse
   • To assess histologic transition or changes in chronicity/activity indices 6

Common Pitfalls to Avoid

• Delaying genetic testing in suspected congenital/infantile cases 1
• Treating based on serum albumin levels alone rather than clinical indicators of hypovolaemia 6, 1
• Overreliance on immunosuppression for genetic forms of nephrotic syndrome 1
• Fluid overload due to excessive fluid administration 1
• Inadequate thromboprophylaxis in high-risk patients
• Failure to monitor for and prevent infections in immunosuppressed patients

By following these evidence-based recommendations and avoiding common pitfalls, outcomes for patients with nephritic and nephrotic syndromes can be optimized with reduced morbidity and mortality.