What is the differential diagnosis (ddx) and management for a patient presenting with Acute Kidney Injury (AKI) and urinary dysmorphic red cells?

Differential Diagnosis of AKI with Dysmorphic Red Cells

The presence of dysmorphic red blood cells in urine with AKI indicates glomerular disease, most commonly acute glomerulonephritis, and requires urgent evaluation with urinalysis, serologic testing, and consideration for kidney biopsy. 1

Primary Differential Diagnosis

The finding of dysmorphic RBCs (particularly acanthocytes/G1 cells) localizes bleeding to the glomerulus and narrows your differential significantly 1:

Glomerulonephritis Syndromes

• Post-infectious glomerulonephritis - Most commonly post-streptococcal, but can follow other bacterial, viral, or parasitic infections 2
• IgA nephropathy (Berger's disease) - Often presents with gross hematuria concurrent with upper respiratory infections 2
• Anti-GBM disease (Goodpasture syndrome) - Rapidly progressive glomerulonephritis with or without pulmonary hemorrhage 3
• ANCA-associated vasculitis - Including granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis 3
• Lupus nephritis - In patients with systemic lupus erythematosus 3
• Membranoproliferative glomerulonephritis - Can be primary or secondary to infections, autoimmune disease, or complement disorders 3

Other Glomerular Causes

• Thin basement membrane disease - Usually presents with persistent microscopic hematuria rather than AKI 2
• Alport syndrome - Hereditary nephritis, typically with family history and hearing loss 2

Essential Diagnostic Workup

Minimal Dataset (Tier 1) 1

• Urinalysis with microscopy - Quantify dysmorphic RBCs (>50 RBCs per high-power field suggests glomerular disease), look for RBC casts (pathognomonic for glomerulonephritis), and assess for proteinuria 1
• Quantitative proteinuria - 24-hour urine protein or spot urine protein-to-creatinine ratio (>500 mg/day suggests structural kidney injury) 1
• Serum creatinine and electrolytes - Serial measurements to stage AKI severity and track trajectory 1, 2
• Complete blood count - Assess for anemia (may indicate chronic process or hemolysis) and thrombocytopenia 1
• Renal ultrasound - Evaluate kidney size (small kidneys suggest chronic disease), exclude obstruction, and assess for structural abnormalities 1

Advanced Serologic Testing (Tier 2) 1

• Complement levels (C3, C4) - Low in post-infectious GN, lupus nephritis, and MPGN 2
• Anti-streptolysin O (ASO) and anti-DNase B titers - Elevated in post-streptococcal GN 2
• ANCA panel - c-ANCA (PR3) and p-ANCA (MPO) for vasculitis 3
• Anti-GBM antibodies - For Goodpasture syndrome 3
• ANA, anti-dsDNA, anti-Smith antibodies - For lupus nephritis 3
• Serum and urine protein electrophoresis - If considering paraprotein-related disease 1
• Hepatitis B and C, HIV serologies - Can cause glomerulonephritis 3

Kidney Biopsy Indications (Tier 3) 1

• Rapidly progressive AKI with dysmorphic RBCs and unclear etiology 1
• AKI not responding to supportive measures within 48-72 hours 1
• Significant proteinuria (>500 mg/day) with dysmorphic RBCs 1
• Need for definitive diagnosis to guide immunosuppressive therapy 1

Critical Management Principles

Immediate Actions 1, 2

• Discontinue all nephrotoxic agents - NSAIDs, aminoglycosides, contrast media, ACE inhibitors/ARBs (temporarily), and any herbal/over-the-counter medications 1
• Assess volume status - Examine for hypovolemia or volume overload; correct appropriately with isotonic crystalloids or diuretics 1, 2
• Monitor blood pressure - Both lying and standing to assess for orthostatic hypotension 1

Nephrology Consultation 4

• Urgent consultation indicated for dysmorphic RBCs with AKI, as this suggests glomerulonephritis requiring potential immunosuppressive therapy 4
• Kidney biopsy planning should occur early if diagnosis remains unclear after initial workup 1

Monitoring During Evaluation 1, 4

• Daily serum creatinine until stabilization or diagnosis established 1
• Urine output monitoring - Oliguria (<0.5 mL/kg/h for 6 hours) worsens AKI staging 4
• Serial urinalysis - Track RBC casts and degree of hematuria 2

Common Pitfalls to Avoid

• Do not assume prerenal AKI - Dysmorphic RBCs indicate intrinsic glomerular disease, not prerenal azotemia; volume expansion alone will not resolve this 2, 3
• Do not delay serologic testing - Some glomerulonephritides (particularly anti-GBM disease and ANCA vasculitis) are rapidly progressive and require urgent immunosuppression 3
• Do not confuse with simple hematuria - Dysmorphic RBCs (especially >40% of total RBCs) and RBC casts are specific for glomerular bleeding, not lower urinary tract sources 2
• Do not overlook medication history - Include prescribed drugs, over-the-counter medications, herbal supplements, and recreational substances 1

Follow-Up After Acute Phase 1

• Reassess renal function at 3 months - Even if AKI resolves, patients remain at increased risk for CKD development 1, 5
• Monitor for proteinuria and hematuria - Persistent abnormalities may indicate ongoing glomerular disease 1
• Nephrology follow-up - Essential for patients with glomerulonephritis, as many require long-term immunosuppression and monitoring 1