Management of Hematuria with Proteinuria and Cellular Casts
The presence of RBCs, cellular casts, and 3+ proteinuria strongly indicates glomerular disease requiring immediate nephrology referral and renal biopsy for definitive diagnosis and treatment. 1
Initial Diagnostic Workup
- Quantify proteinuria with a 24-hour urine collection or spot urine protein-to-creatinine ratio to determine exact protein excretion (3+ proteinuria likely exceeds 1g/day) 1, 2
- Assess renal function with serum creatinine and estimated GFR 1
- Evaluate for systemic diseases associated with glomerulonephritis through laboratory testing: 1
- Complete blood count
- Comprehensive metabolic panel
- Complement levels (C3, C4)
- Antinuclear antibody (ANA)
- Anti-double stranded DNA antibodies
- Anti-neutrophil cytoplasmic antibodies (ANCA)
- Hepatitis B and C serology
- HIV testing
- Serum and urine protein electrophoresis
Renal Biopsy Indication
- Renal biopsy is indispensable as clinical, serological, or laboratory tests cannot accurately predict renal biopsy findings 3
- The combination of hematuria (4 RBCs/hpf), cellular casts, and significant proteinuria (3+) strongly indicates the need for histological evaluation 1
- Biopsy findings will determine specific diagnosis, prognosis, and guide treatment decisions 1
Potential Diagnoses Based on Clinical Presentation
- Lupus nephritis - especially with "full-house" immunofluorescence staining pattern 3
- ANCA-associated vasculitis - particularly if areas of fibrinoid necrosis are present 3
- IgA nephropathy - common cause of hematuria with proteinuria 1
- Membranoproliferative glomerulonephritis 1
- Crescentic glomerulonephritis 1
Treatment Considerations
For lupus nephritis class III-IV, initial therapy options include: 3
- Mycophenolic acid (mycophenolate mofetil target dose: 3 g/day for 6 months) with glucocorticoids
- Low-dose intravenous cyclophosphamide (total dose 3g over 3 months) with glucocorticoids
For patients with contraindications to high-dose corticosteroids (e.g., uncontrolled diabetes, psychiatric conditions, severe osteoporosis), calcineurin inhibitors can be considered as first-line therapy 3
For significant proteinuria (>1 g/day), ACE inhibitor or ARB treatment should be initiated with uptitration depending on blood pressure, targeting <125/75 mmHg 2
Monitoring and Follow-up
Monitor response to therapy through: 3
- Proteinuria levels (target <0.5 g/24h)
- Renal function (serum creatinine)
- Urinalysis for resolution of hematuria and casts
If worsening occurs during the first 3 months of treatment (rising serum creatinine, worsening proteinuria), consider changing to alternative therapy or repeat kidney biopsy 3
Important Caveats
- Do not attribute hematuria solely to anticoagulation therapy when cellular casts and significant proteinuria are present 1
- Do not delay nephrology referral, as early intervention may prevent disease progression 1
- Normal renal ultrasound does not exclude glomerular disease 1
- While diabetic nephropathy typically presents with proteinuria without hematuria, significant hematuria with red cell casts can occasionally be a feature of diabetic nephropathy 4