What is the management approach for nephritic syndromes?

Management Approach for Nephritic Syndromes

Patients with nephritic syndrome should be rapidly referred to specialized nephrology teams in tertiary centers for multidisciplinary management, as this condition requires expertise and a combined approach that can only be guaranteed in centers with experience treating this condition. 1

Initial Diagnostic Workup

• Perform comprehensive diagnostic evaluation including:

  • Clinical and biological assessment to confirm nephritic-range proteinuria, hematuria, hypertension, and possible acute kidney injury 2, 3
  • Infectious screening to identify potential infectious causes of nephritic syndrome 1
  • Genetic testing as a first-line diagnostic measure, preferably using massively parallel sequencing or whole-exome sequencing 1
  • Extended diagnostic workup to identify non-kidney manifestations of hereditary forms (neurological status, sight, hearing, dysmorphic features) 1

• Consider kidney biopsy when:

  • Genetic and infectious screening are negative 1
  • Diagnosis remains unclear despite initial workup 4, 5
  • Histological confirmation is needed to guide therapy 4

Treatment Approach Based on Etiology

For Infectious Nephritic Syndrome

• Treat with specific antimicrobial agents targeted at the identified pathogen 1
• Monitor for resolution of nephritic features following treatment 1

For Non-Genetic Nephritic Syndrome

• If infection and genetic screening are negative, consider kidney biopsy and potential trial of immunosuppressant therapy 1
• Approach should be individualized and stepwise, with conservative management as an appropriate alternative to early invasive interventions 1

For Genetic Forms

• Immunosuppressive agents are generally not recommended as they typically do not target the underlying genetic abnormalities 1
• Focus on supportive care and management of complications 1

Supportive Management

Fluid and Albumin Management

• Avoid intravenous fluids and saline when possible 1
• Concentrate oral fluid intake if necessary to avoid marked edema 1
• Administer albumin infusions only based on clinical indicators of hypovolemia (oliguria, acute kidney injury, prolonged capillary refill time, tachycardia, hypotension) or failure to thrive, not based solely on serum albumin levels 1, 4
• Administer furosemide at the end of albumin infusion to enhance diuresis 4

Anti-Proteinuric Therapy

• Use renin-angiotensin-aldosterone system (RAAS) antagonists (ACE inhibitors or ARBs) to reduce glomerular protein loss 1
• Consider combination therapy with ACE inhibitors and indomethacin in selected cases 1
• If using potassium-sparing diuretics, prefer ENaC blockers like amiloride over spironolactone 1

Prevention of Complications

• Avoid central venous lines when possible due to high thrombosis risk 1
• If central venous access is required, administer prophylactic anticoagulation for as long as the line is in place 1
• Monitor for and treat hyperlipidemia, which commonly accompanies nephrotic syndrome 6, 2
• Implement measures to prevent infections, which patients with nephrotic syndrome are at increased risk for 6, 5

Long-term Management

• When stable, transition to ambulatory management to:

  • Increase quality of life 1
  • Decrease risk of nosocomial infections 1
  • Reduce treatment costs 1

• Consider home administration of regular albumin infusions by trained parents when necessary 1

• Early referral to transplant center for patients with progressive disease to:

  • Minimize time on dialysis 1
  • Facilitate the transplant process 1

• Consider nephrectomy in patients with:

  • Persistent hypovolemia despite optimal management 1
  • Thrombosis 1
  • Failure to thrive 1
  • Progression to kidney failure (CKD G5) with persistent nephrotic syndrome 1
  • WT1 pathogenic variant 1

Special Considerations

• For congenital membranous nephropathy due to maternal anti-NEP antibodies, specific management approaches may be required 1

• For frequently relapsing nephrotic syndrome, consider:

  • Rituximab (375 mg/m² IV) as a steroid-sparing agent 4
  • Alternative therapies such as calcineurin inhibitors, mycophenolate mofetil, cyclophosphamide, or levamisole if rituximab is unavailable or contraindicated 4