What is the appropriate management for a third‑trimester pregnant woman who has developed nephrotic‑range proteinuria (≥3.5 g/24 h)?

Management of Nephrotic-Range Proteinuria in Third Trimester

In the third trimester, nephrotic-range proteinuria (≥3.5 g/24h) most likely represents severe preeclampsia and mandates immediate blood pressure assessment, maternal stabilization with antihypertensives and magnesium sulfate if indicated, and delivery planning based on gestational age and presence of severe features—not on the degree of proteinuria itself. 1

Immediate Assessment Required

Blood Pressure Measurement

• Measure blood pressure immediately and confirm if ≥140/90 mmHg, as proteinuria without hypertension after 20 weeks does not constitute preeclampsia 2, 1
• Severe hypertension is defined as ≥160/110 mmHg and requires urgent treatment within 15 minutes 1
• The combination of nephrotic-range proteinuria with hypertension after 20 weeks confirms preeclampsia with severe features 2, 1

Gestational Age Determination

• If ≥37 weeks, proceed directly to delivery after maternal stabilization 1
• If 34-37 weeks with severe features (massive proteinuria + hypertension), deliver within 24-48 hours after stabilization 1
• If <34 weeks, assess for additional severe features requiring expedited delivery 1

Acute Management

Antihypertensive Therapy

• If BP ≥140/90 mmHg: Initiate oral methyldopa, labetalol, or nifedipine targeting diastolic 85 mmHg and systolic 110-140 mmHg 1
• If BP ≥160/110 mmHg: Urgent treatment with oral nifedipine or IV labetalol/hydralazine in a monitored setting, with BP confirmation within 15 minutes 1

Seizure Prophylaxis

• Strongly consider magnesium sulfate given nephrotic-range proteinuria, which dramatically increases eclampsia risk when combined with other severe features 1
• Magnesium sulfate is indicated for seizure prophylaxis in severe preeclampsia 1

Thromboprophylaxis

• Consider thromboprophylaxis for massive proteinuria (>5 g/24h), as this represents a nephrotic-syndrome-like state with increased venous thromboembolism risk 2, 1
• A 24-hour urine collection is indicated specifically to confirm nephrotic syndrome for thromboprophylaxis decisions 2

Fetal Assessment

• Perform ultrasound evaluation of fetal growth, as massive proteinuria (>5 g/24h) is associated with placental insufficiency and more severe neonatal outcomes 2, 1
• Conduct non-stress testing to monitor fetal well-being, as fetal compromise may be the earliest sign of severe preeclampsia 1

Critical Management Principles

Do Not Base Delivery Decisions on Proteinuria Quantification

• The degree of proteinuria provides little additional risk stratification beyond identifying high-risk disease 2, 1
• Delivery decisions should be driven by maternal organ dysfunction, fetal status, and gestational age rather than absolute proteinuria levels 1, 3
• Proteinuria is not independently predictive of adverse outcomes, and exclusive proteinuric criteria should not guide preterm delivery 3, 4
• Do not repeat proteinuria measurements to guide delivery timing, as proteinuria fluctuates and does not predict outcomes 1, 4

Monitor for Maternal Warning Symptoms

• New-onset headache: Independent risk factor for progression to eclampsia requiring urgent assessment and likely expedited delivery 1
• Epigastric or upper-quadrant pain with vomiting: Independently predicts serious maternal morbidity necessitating rapid evaluation 1
• Visual disturbances: Suggest cerebral edema and impending eclampsia requiring immediate intervention 1
• Any of these symptoms mandate prompt maternal assessment and often accelerated delivery 1

Laboratory Surveillance

• Note that hypertension or proteinuria may be absent in 10-15% of patients with HELLP syndrome and 38% of patients with eclampsia 3
• Monitor for end-organ damage, as severity of blood pressures and presence of end-organ damage influence outcomes more than protein excretion 4

Postpartum Management

• Close monitoring for 48-72 hours postpartum is necessary, as 20% of HELLP cases occur within 48 hours of delivery 1
• Reassess proteinuria at 3 months postpartum; if persistent, this confirms underlying primary renal disease requiring nephrology referral 5, 6, 1
• If proteinuria resolves completely, the diagnosis was likely gestational proteinuria or preeclampsia-related 6

Common Pitfalls to Avoid

• Do not delay delivery based on proteinuria quantification alone—massive proteinuria itself indicates high-risk disease but should not be the sole criterion for delivery timing 1, 3
• Do not assume isolated proteinuria without hypertension is preeclampsia—proteinuria is sufficient but not necessary for preeclampsia diagnosis, but hypertension must be present 2, 4
• Do not continue ACE inhibitors or ARBs if somehow still prescribed—these are strictly contraindicated in pregnancy due to severe fetotoxicity 5, 6