How to manage nephrotic range proteinuria in pregnancy?

Management of Nephrotic Range Proteinuria in Pregnancy

Nephrotic range proteinuria in pregnancy requires careful assessment to distinguish between preeclampsia and primary renal disease, with management tailored to the underlying etiology and focused on maternal-fetal outcomes. 1

Initial Assessment and Diagnosis

• Diagnostic Criteria:

  • Protein/creatinine ratio ≥30 mg/mmol is considered abnormal 1
  • Nephrotic range proteinuria is typically defined as ≥3g/24h
  • Clinical proteinuria is classified as ≥300 mg/g 1

• Essential Evaluation:

  • Blood pressure measurements (severe hypertension defined as ≥160/110 mmHg)
  • Laboratory tests: complete blood count, liver function, renal function
  • Urinalysis with protein/creatinine ratio (preferred screening method) 1
  • Initial ultrasound to confirm fetal well-being 1

Management Algorithm Based on Etiology

1. Preeclampsia-Related Proteinuria

• Hospitalization for initial assessment if protein/creatinine ratio indicates preeclampsia 1
• Blood pressure control:
  • First-line: oral methyldopa, labetalol, nifedipine
  • Second/third-line: hydralazine, prazosin 1
  • ACE inhibitors, ARBs, and direct renin inhibitors are strictly contraindicated due to fetotoxicity 1
• Magnesium sulfate for women with severe hypertension or neurological signs/symptoms 1
• Delivery indications:
  • Gestational age ≥37 weeks
  • Complications: repeated severe hypertension, progressive thrombocytopenia, neurological complications 1

2. Primary Renal Disease

• Focal Segmental Glomerulosclerosis (FSGS):

  • Consider immunosuppressive therapy with prednisone or calcineurin inhibitors 1
  • Note that FSGS in pregnancy often has adverse renal outcomes despite treatment 2

• Lupus Nephritis:

  • Treatment with corticosteroids combined with cyclophosphamide or mycophenolate mofetil 1
  • Monitor response within first 3 months 1

• Membranous Nephropathy:

  • May first present during pregnancy and can progress to nephrotic syndrome 3
  • Steroid therapy may be required but response can be variable 3

Renal Biopsy Considerations

• Indications for biopsy:
  • Proteinuria >1 g/day with no obvious cause 1
  • Proteinuria >0.5 g/day with hematuria or declining kidney function 1
  • Lower threshold (>500 mg/day) in lupus patients 1
  • New onset proteinuria before 20 weeks' gestation suggesting underlying kidney disease 4

Monitoring and Follow-up

• During Pregnancy:

  • Laboratory tests at least twice weekly 1
  • More frequent fetal monitoring if growth restriction is present 1

• Postpartum:

  • Close monitoring for at least 3 days 1
  • Continue antihypertensive medications as needed 1
  • Reassess renal function and proteinuria at 3 months to detect underlying renal disease 1
  • Note that physiological changes may persist for 5-6 months postpartum 4

Important Considerations and Pitfalls

• Differential Diagnosis: New-onset proteinuria before 20 weeks' gestation suggests underlying kidney disease rather than preeclampsia 4

• Maternal Risks:

  • High rate of cesarean section (63%) and high dependency unit admission (34%) in women with nephrotic range proteinuria 5
  • Increased long-term cardiovascular risks 1

• Fetal Risks:

  • Birth weight below 5th percentile in 33% of cases with nephrotic range proteinuria 5
  • Massive proteinuria (>5g/24h) associated with worse neonatal outcomes 1

• Long-term Follow-up:

  • Annual medical review is advised lifelong 1
  • Achieve pre-pregnancy weight within 12 months 1
  • Encourage healthy lifestyle with regular exercise 1
  • Prompt referral to nephrologist for eGFR <30 mL/min/1.73m², uncertain etiology, difficult management, or rapidly progressing kidney disease 1