Nephrotic Syndrome in Pregnancy

Nephrotic syndrome in pregnancy is heavy proteinuria (above 3.5 g/day, urine protein to creatinine ratio above 300 mg/mmol), low serum albumin (below 30 g/L), oedema and raised lipids. Causes include minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, lupus nephritis, diabetic nephropathy and HIV associated nephropathy. It matters because it carries high risks of preeclampsia, thrombosis, preterm birth and growth restriction.

• Pregnancy can worsen proteinuria and oedema.
• Albumin below 25 g/L carries high thrombosis risk.
• Preeclampsia can mimic or complicate it.

Women have facial and leg swelling, ascites, weight gain, foamy urine and tiredness, with hypertension in many. Look for infection, thrombosis and hypovolaemia.

• Periorbital oedema in the morning.
• Pleural effusion and ascites in severe disease.
• Differential diagnosis: preeclampsia, normal pregnancy oedema, heart failure, liver disease, malnutrition, protein losing enteropathy.
• Complications: venous thrombosis, preeclampsia, infection, acute kidney injury, growth restriction, preterm birth, stillbirth, hypovolaemia.

The approach is quantification of proteinuria with cause finding.

• Urine protein to creatinine ratio, 24 hour urine protein, urinalysis with microscopy, serum albumin, cholesterol, creatinine, electrolytes.
• Full blood count, complement (C3 and C4), anti dsDNA, antinuclear antibody, HIV, hepatitis B and C tests, glucose, HbA1c.
• Renal ultrasound; kidney biopsy before 28 weeks only if treatment would change.
• Uterine artery Doppler at 20 to 24 weeks; growth scans every 4 weeks.

The principle is oedema control, thromboprophylaxis, blood pressure control and disease specific treatment.

• Supportive: salt restriction of 2 g sodium daily; protein intake of 1 g/kg daily; leg elevation; compression stockings of 20 to 30 mmHg; monthly urine culture; daily weight.
• Pharmacological: furosemide 20 to 80 mg oral or IV daily for symptomatic oedema; albumin 20 percent 100 mL IV with furosemide 40 mg for refractory oedema; enoxaparin 40 mg subcutaneous daily (60 mg for weight 91 to 130 kg) for albumin below 25 g/L, and for 6 weeks postpartum; aspirin 150 mg oral at night from 12 weeks to 36 weeks; prednisolone 1 mg/kg oral daily (maximum 60 mg) for minimal change disease, tapered over 8 to 12 weeks; tacrolimus 1 to 2 mg oral 12-hourly adjusted to trough level for steroid resistant disease; labetalol 200 mg oral every 8 to 12 hours (maximum 2.4 g daily) or nifedipine modified release 30 to 60 mg daily for blood pressure above 140/90 mmHg; stop ACE inhibitors, angiotensin receptor blockers and statins; amoxicillin 500 mg oral 8-hourly for infection.
• Procedures: ultrafiltration or dialysis for refractory fluid overload; delivery at 37 weeks, earlier for preeclampsia, falling kidney function or fetal compromise.
• Special groups: diabetic nephropathy needs insulin and HbA1c below 6.5 percent; HIV associated nephropathy needs antiretroviral therapy chosen with HIV specialist advice, avoiding tenofovir disoproxil if creatinine clearance is below 50 mL/minute; lupus nephritis needs hydroxychloroquine 200 mg oral 12-hourly and prednisolone.
• Red flags: blood pressure above 160/110 mmHg, leg swelling on one side, breathlessness, oliguria, fever, headache, reduced fetal movements.
• Follow-up: review every 2 weeks with creatinine, albumin and urine protein; fetal growth scans; review at 6 weeks postpartum and refer to nephrology.