What are the possible causes of left-sided flank pain with no urinary symptoms and a negative urinalysis?

Differential Diagnosis of Left-Sided Flank Pain with Negative Urinalysis

When flank pain presents without urinary symptoms and a negative urinalysis, you must systematically exclude non-renal causes before attributing symptoms to the urinary tract, as approximately one-third of patients with flank pain have extraurinary pathology. 1, 2

Initial Diagnostic Framework

The absence of urinary symptoms and negative urinalysis significantly shifts the differential away from typical urolithiasis and urinary tract infection, though these cannot be completely excluded. Obtain a non-contrast CT abdomen and pelvis as the primary diagnostic study, which has 98-100% sensitivity and specificity for stones while simultaneously identifying alternative diagnoses in approximately one-third of patients. 1, 2

Key Clinical Distinctions to Establish

• Positional pain characteristics: Pain that worsens after prolonged static positioning or with external pressure strongly suggests musculoskeletal origin involving paraspinal muscles, facet joints, or referred pain from lumbar spine pathology 1, 3

• Classic renal colic: Presents as colicky, wave-like severe pain independent of body position, typically radiating to the groin or genitals rather than remaining localized 1, 3

• Radiation pattern: Pain radiating to unusual locations (such as the scapula) raises concern for referred pain from diaphragmatic irritation, splenic pathology, or pancreatic tail processes on the left side 3

Primary Differential Diagnoses

Urologic Causes (Despite Negative UA)

• Urolithiasis: Up to 15% of patients with flank pain from renal stones have negative urinalysis and no history of stones 4. Small stones may not cause hematuria, and early obstruction may not yet show pyuria 2

• Intermittent ureteropelvic junction obstruction: Can present with intermittent flank pain without persistent urinary findings, sometimes caused by crossing accessory renal vessels 5

• Renal infarction: Spontaneous renal artery dissection or thrombosis presents with acute flank pain and is frequently missed without contrast-enhanced imaging 6

• Page kidney: Subcapsular hematoma causing renal parenchymal compression can present with flank pain and may show hematuria, though urinalysis can be negative 7

• Nutcracker syndrome: Left renal vein compression between the aorta and superior mesenteric artery causes flank pain and may present without consistent hematuria 8

Gastrointestinal Causes

• Left colonic diverticulitis: Can present as left-sided flank pain mimicking renal pathology 1

• Gastroenteritis and colitis: Including inflammatory bowel disease, can manifest with flank pain 1

• Splenic pathology: Splenic infarction, subcapsular hematoma, or splenomegaly can cause left flank pain with referred pain patterns 3

• Pancreatic tail pathology: Pancreatitis or masses in the pancreatic tail may present with left flank pain 3

Musculoskeletal Causes

• Rib cage pathology: Vitamin D deficiency causing osteomalacia of the ribs presents with flank pain and distinct tenderness over the costal margin rather than the renal angle proper 9. This is frequently unrecognized, with very low vitamin D levels found in patients with rib tenderness and flank pain 9

• Lumbar spine pathology: Facet joint arthropathy, disc disease, or radiculopathy can cause referred flank pain that is position-dependent 1, 3

• Paraspinal muscle strain: Typically worsens with movement and palpation 1

Gynecologic Causes (in Women)

• Benign adnexal masses: Can cause left-sided flank pain 1

• Pelvic congestion syndrome: May present with chronic flank pain 1

Critical Red Flags Requiring Urgent Evaluation

• Fever, chills, or signs of systemic infection: Despite negative urinalysis, up to 20% of patients with acute pyelonephritis lack bladder symptoms 4. Consider urine culture even with negative urinalysis if clinical suspicion is high 4

• Inability to urinate or decreased urine output: Suggests complete obstruction requiring urgent intervention 1, 3

• Hemodynamic instability: Consider vascular catastrophe including aortic pathology or renal artery dissection 3, 6

Recommended Diagnostic Algorithm

First-Line Imaging

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

• Detects stones with 98-100% sensitivity regardless of size or composition 2
• Identifies extraurinary causes in one-third of patients 1, 2
• Evaluates for bowel pathology, masses, and musculoskeletal abnormalities 4

When to Add Contrast

If non-contrast CT is non-diagnostic and patient has no history of urolithiasis with negative urinalysis, obtain contrast-enhanced CT 4, 2:

• Better characterizes alternative diagnoses including vascular pathology 6
• Essential for detecting renal infarction, which requires contrast for diagnosis 6
• 15% of patients with flank pain, negative stone history, and negative urinalysis have non-renal diagnoses requiring contrast for identification 4

Alternative Imaging

• Ultrasound with Doppler: Consider for radiation concerns or when evaluating for nutcracker syndrome, though sensitivity is lower (45%) compared to CT 3, 8

• MRI: Reserved for equivocal cases or when radiation must be avoided 4

Common Pitfalls to Avoid

• Anchoring on urolithiasis: The combination of flank pain with negative urinalysis and no urinary symptoms should prompt broader differential consideration 7, 6

• Assuming negative urinalysis excludes urologic pathology: Small stones, early obstruction, and intermittent obstruction may not produce urinalysis abnormalities 4, 2, 5

• Ordering contrast-enhanced CT first: This may obscure small renal stones within the collecting system 2. Start with non-contrast unless clinical presentation strongly suggests non-urologic pathology 4

• Missing musculoskeletal causes: Failure to palpate the costal margin (rather than just the renal angle) may miss rib pathology from vitamin D deficiency 9

• Delayed imaging during symptomatic episodes: For intermittent symptoms, imaging during pain-free periods may be falsely negative, particularly for intermittent obstruction 5

Physical Examination Pearls

• Distinguish costal margin tenderness from renal angle tenderness: Tenderness over the tips of the lowermost ribs suggests rib cage pathology rather than renal disease and warrants vitamin D level assessment 9

• Assess pain with position changes: Musculoskeletal pain typically varies with position, while renal colic is position-independent 1, 3

• Evaluate for systemic signs: Even without urinary symptoms, fever or systemic toxicity may indicate pyelonephritis, as 20% of cases lack bladder symptoms 4