What is the diagnosis and management for a 35-year-old female with anasarca, significant proteinuria (Protein to Creatinine Ratio (PCR) elevated), hypoalbuminemia (low albumin), hypertriglyceridemia (elevated triglycerides), low serum Complement 3 (C3) level, impaired renal function (elevated creatinine), hematuria (blood in urine), and proteinuria (excess protein in urine)?

Diagnosis: Nephrotic Syndrome with Acute Kidney Injury

This patient has nephrotic syndrome with significant renal impairment requiring urgent nephrology referral within 2 weeks and likely renal biopsy to determine the underlying glomerular disease and guide immunosuppressive therapy. 1, 2

Clinical Presentation Confirms Nephrotic Syndrome

This 35-year-old female meets all diagnostic criteria for nephrotic syndrome:

• Massive proteinuria: UPCR of 30.41 g/g (30,410 mg/g) far exceeds the nephrotic threshold of >3.5 g/day or >3,500 mg/g 2, 3
• Severe hypoalbuminemia: Albumin of 14 g/L (1.4 g/dL) is well below the diagnostic threshold of <30 g/L 2, 3
• Anasarca: Generalized edema representing the third component of the classic triad 2, 4
• Hypertriglyceridemia: 7.20 mmol/L confirms the typical lipid abnormality seen in nephrotic syndrome 2, 3

Concerning Features Requiring Urgent Action

The elevated creatinine of 274.20 μmol/L (approximately 3.1 mg/dL) with hematuria indicates acute kidney injury superimposed on nephrotic syndrome, which significantly increases urgency. 1

• The combination of 4+ proteinuria with 1+ hematuria suggests active glomerular inflammation rather than minimal change disease 1, 5
• Normal serum C3 at 1.890 g/L makes post-infectious glomerulonephritis and lupus nephritis less likely, though does not exclude them 1, 6
• The presence of both nephrotic-range proteinuria and hematuria mandates renal biopsy to establish the specific glomerular disease 1, 5

Immediate Management Steps

Urgent Nephrology Referral (Within 2 Weeks)

Refer immediately to nephrology for renal biopsy, as this patient meets multiple high-risk criteria: 1, 5, 2

• Nephrotic-range proteinuria >3.5 g/day with elevated creatinine 1, 5
• Active urinary sediment with hematuria suggesting glomerulonephritis 5
• Need to determine if this is membranous nephropathy, focal segmental glomerulosclerosis, or another primary glomerular disease 2, 4

Conservative Management While Awaiting Nephrology

Initiate supportive care immediately, but do NOT start immunosuppressive therapy before biopsy confirmation: 1

• Blood pressure control: Target <125/75 mmHg using ACE inhibitors or ARBs as first-line agents, as they reduce proteinuria independent of blood pressure lowering 1, 7
• Sodium restriction: Limit to <2 g/day to manage edema 1
• Diuretics: Use loop diuretics (furosemide) for symptomatic edema management 8, 2
• Protein restriction: Moderate dietary protein restriction (0.8 g/kg/day) 1
• Statin therapy: Initiate for hyperlipidemia management 2, 4

Critical Monitoring and Complications

Monitor closely for life-threatening complications of nephrotic syndrome: 2, 4

• Thromboembolism risk: This patient is at high risk given severe hypoalbuminemia and massive proteinuria; consider prophylactic anticoagulation if albumin <20 g/L (this patient is at 14 g/L) 2, 4
• Infection susceptibility: Monitor for signs of bacterial infection, particularly spontaneous bacterial peritonitis and cellulitis 2, 4
• Acute kidney injury progression: Check serum creatinine and electrolytes within 1-2 weeks 1
• Volume status: Daily weights and assessment for worsening edema 2

Renal Biopsy and Definitive Diagnosis

Renal biopsy is mandatory before initiating immunosuppressive therapy to determine the specific glomerular disease: 1, 2

The biopsy will differentiate between:

• Membranous nephropathy: Most common cause in white adults, typically presents with isolated nephrotic syndrome 2, 4
• Focal segmental glomerulosclerosis: More common in African ancestry populations, often with hematuria 2, 4
• Minimal change disease: Less likely given the hematuria and renal impairment 2, 4
• Secondary causes: Lupus nephritis (less likely with normal C3), diabetic nephropathy, or amyloidosis 2, 6

Immunosuppressive Therapy Considerations

Do NOT initiate immunosuppressive therapy until after renal biopsy confirms the diagnosis, but be prepared to start treatment based on biopsy results: 1, 8

Criteria for Immunosuppression (Post-Biopsy)

If biopsy confirms primary glomerular disease, immunosuppression is indicated when: 1

• Urinary protein excretion persistently exceeds 4 g/day (this patient has ~30 g/day) 1
• Severe, disabling symptoms related to nephrotic syndrome (anasarca qualifies) 1
• Rising creatinine by 30% or more within 6-12 months with eGFR >25-30 mL/min/1.73 m² 1

Contraindications to Immunosuppression

Do NOT use immunosuppressive therapy if: 1

• Serum creatinine persistently ≥3.5 mg/dL (this patient is at 3.1 mg/dL, borderline) 1
• eGFR ≤30 mL/min/1.73 m² 1
• Concomitant severe or life-threatening infections 1
• Small echogenic kidneys on ultrasound 1

First-Line Immunosuppressive Regimen (If Indicated)

If biopsy confirms membranous nephropathy or FSGS and immunosuppression is warranted, use the modified Ponticelli regimen: 1, 8

• Alternating monthly cycles of oral and IV corticosteroids with oral cyclophosphamide for 6 months 1, 8
• Cyclophosphamide is preferred over chlorambucil 1
• Adjust cyclophosphamide dose according to age and eGFR 1
• Corticosteroids are FDA-approved for inducing remission of proteinuria in nephrotic syndrome 8

Common Pitfalls to Avoid

• Do not delay nephrology referral: This patient has multiple high-risk features requiring urgent specialist evaluation 5, 2
• Do not start immunosuppression empirically: Renal biopsy must confirm the diagnosis first, as treatment varies significantly by histologic type 1
• Do not overlook thromboembolism prophylaxis: With albumin at 14 g/L and massive proteinuria, this patient is at extremely high risk for venous thrombosis 2, 4
• Do not use ACE inhibitors/ARBs without monitoring: Check creatinine and potassium within 1-2 weeks of initiation to detect hyperkalemia or acute deterioration 1, 7
• Do not assume this is minimal change disease: The presence of hematuria and renal impairment suggests a more aggressive glomerular disease 2, 4