What is the appropriate workup and management for a patient with flank pain and proteinuria, considering their age, medical history, and physical examination findings?

Workup for Flank Pain with Proteinuria

Non-contrast CT of the abdomen and pelvis is the imaging study of choice for evaluating flank pain, achieving 98-100% sensitivity and specificity for detecting urinary stones while identifying alternative diagnoses in approximately one-third of patients. 1, 2, 3 However, the presence of proteinuria requires additional evaluation beyond standard stone workup, as this combination may indicate glomerular disease, renal vein thrombosis, or other renal parenchymal pathology rather than simple urolithiasis.

Initial Clinical Assessment

Key Historical and Physical Examination Features

• Pain characteristics: Classic renal colic presents as colicky, wave-like severe pain independent of body position, radiating to groin or genitals with abrupt onset 2. Pain occurring after prolonged static positioning suggests musculoskeletal origin 2
• Urinary symptoms: Hematuria (even microscopic) shifts probability toward stone disease 2, but proteinuria with flank pain raises concern for glomerular pathology, renal vein thrombosis, or subcapsular hematoma 4, 5
• Red flags requiring urgent evaluation: Fever, chills, hemodynamic instability, inability to urinate, or decreased urine output 2, 3
• Special populations: Consider ectopic pregnancy in women with delayed menses presenting with flank pain 2

Urinalysis Interpretation

• Proteinuria quantification: Obtain spot urine protein-to-creatinine ratio or 24-hour urine collection to determine if nephrotic-range proteinuria (>3.5 g/day) is present 6
• Urinary sediment analysis: Presence of leukocyturia with negative leukocyte dipstick test and milky urine should raise suspicion for chyluria 7
• Important caveat: Over 20% of patients with confirmed urinary stones may have negative urinalysis, so normal urinalysis does not exclude significant urologic pathology 3

Imaging Strategy

First-Line Imaging

Non-contrast CT abdomen and pelvis is the gold standard initial imaging modality 1, 2, 3, 8:

• Detects ureteral stones with 98-100% sensitivity and specificity regardless of size, location, or chemical composition 1, 3, 8
• Identifies extraurinary causes of flank pain in approximately one-third of patients 2, 8
• Can detect subcapsular hematomas (Page kidney), renal vein thrombosis, and other parenchymal abnormalities 4
• Completed within 5 minutes without need for contrast agent 8

Alternative Imaging Considerations

Ultrasound with color Doppler should be considered as first-line in specific populations 1, 2, 3:

• Pregnant patients to avoid radiation exposure 1, 2
• Patients with radiation concerns or known renal disease 3
• Can evaluate for hydronephrosis (up to 100% sensitive, 90% specific), increased renal echogenicity suggesting chronic kidney disease, and ureteral jets 1
• Absence of hydronephrosis on ultrasound makes larger ureteral stones (>5 mm) less likely 2, 3

CT with IV contrast or CT urography may be indicated 1:

• When non-contrast CT is non-diagnostic and alternative diagnoses are suspected 3
• For comprehensive evaluation of renal parenchyma and vasculature if renal vein thrombosis or other vascular pathology is suspected 5
• Pitfall to avoid: Contrast-enhanced CT can obscure stones within the renal collecting system 3

Additional Diagnostic Workup Based on Proteinuria

Laboratory Evaluation

• Serum creatinine and estimated GFR: Assess baseline renal function 5
• Serum albumin: Determine if nephrotic syndrome is present (hypoalbuminemia with nephrotic-range proteinuria) 1
• Lipid panel: Hyperlipidemia accompanies nephrotic syndrome; hypertriglyceriduria specifically suggests chyluria 7
• Proteinuria characterization: Differentiate albumin, low-molecular weight proteins, and immunoglobulins to distinguish glomerular from tubular proteinuria 6
• Hypercoagulability workup if renal vein thrombosis suspected: Antithrombin III, protein C, protein S levels 5

When to Consider Renal Biopsy

Renal biopsy should be considered when 1:

• Nephrotic-range proteinuria (>3.5 g/day) is present without clear etiology on imaging
• Imaging excludes obstructive uropathy and vascular causes
• Suspicion for glomerular disease (focal segmental glomerulosclerosis, lupus nephritis, or other glomerulonephritides) based on clinical presentation

Management Implications

Immediate Management

• Pain control: Provide rapid analgesia with NSAIDs (diclofenac intramuscular preferred) within 30 minutes, with reassessment within one hour 2, 3
• Failure of analgesia after 1 hour mandates immediate hospital admission 2
• If fever, hemodynamic instability, or signs of sepsis develop: Immediate hospital admission regardless of imaging results 3

Stone-Specific Management

• Stones <5 mm: Typically pass spontaneously with conservative management 2
• Stones >5 mm or complete obstruction: Urgent urology referral within 7-14 days for consideration of endoscopic removal 2, 3
• Instruct patients: Maintain high fluid intake and strain urine to catch stones 2

Proteinuria-Specific Management

• If renal vein thrombosis identified: Consider systemic thrombolytic therapy (urokinase) or anticoagulation, which can resolve proteinuria 5
• If Page kidney (subcapsular hematoma) diagnosed: Conservative management with hypertension control using ACE inhibitors; more invasive measures (evacuation or nephrectomy) reserved for refractory cases 4
• If glomerular disease suspected: Initiate renin-angiotensin-aldosterone system inhibition and consider immunosuppressive therapy based on biopsy results 1

Common Pitfalls to Avoid

• Do not assume all flank pain with proteinuria is nephrolithiasis: The combination warrants broader differential diagnosis including renal vein thrombosis, subcapsular hematoma, and glomerular disease 4, 5
• Do not assume absence of hematuria excludes stone disease: Clinical picture may have evolved 3
• Do not delay imaging in young females: Consider gynecologic causes requiring urgent intervention 2
• Do not miss ectopic pregnancy in women with delayed menses 2
• Do not order contrast-enhanced CT as initial study if stone disease is primary concern: Contrast can obscure stones in collecting system 3