What are the differential diagnoses and treatment guidelines for a patient with flank pain, without hematuria, dysuria, or significant White Blood Cells (WBC) in the urine, but with trace proteinuria on Urinalysis (UA)?

Flank Pain Without Hematuria: Differential Diagnosis and Management

In a patient with flank pain but no hematuria, dysuria, or significant WBC on urinalysis—only trace proteinuria—the differential shifts away from typical urolithiasis and infection toward musculoskeletal causes, renal parenchymal disease, vascular compression syndromes, and less common urologic pathology that requires imaging to exclude.

Key Diagnostic Principle

• The absence of hematuria significantly reduces but does not eliminate urologic causes, as approximately 5-20% of patients with confirmed urinary stones may have negative urinalysis for blood 1, 2.
• However, flank pain without hematuria, dysuria, or pyuria broadens the differential beyond simple stone disease and mandates consideration of alternative diagnoses 1, 3.

Primary Differential Diagnoses

Musculoskeletal Causes (Most Likely in This Presentation)

• Pain occurring after prolonged static positioning or that varies with body position strongly suggests paraspinal muscle strain, facet joint pathology, or referred pain from lumbar spine disease 3.
• Classic renal colic from stones presents as colicky, wave-like severe pain independent of body position, which distinguishes it from musculoskeletal pain 3.

Renal Vascular Compression Syndromes

• Nutcracker syndrome (left renal vein compression between the superior mesenteric artery and aorta) can present with flank pain, trace proteinuria, and intermittent or absent hematuria 4, 5, 6.
• This diagnosis should be considered when there is no obvious cause of proteinuria and flank pain, particularly in younger patients 5, 6.
• Diagnosis requires renal vein ultrasonography with Doppler or venography 4, 5.

Subcapsular Hematoma (Page Kidney)

• Page kidney (compression of renal parenchyma by subcapsular hematoma causing secondary hypertension) can present with flank pain and may have minimal or absent hematuria 7.
• This diagnosis should be considered especially if the patient is found to be hypertensive on evaluation 7.
• Causes include spontaneous hemorrhage, renal cyst rupture, or occult trauma 7.

Urolithiasis (Despite Absent Hematuria)

• Urinary stones remain possible even without hematuria, as 5-20% of confirmed stone cases have negative urinalysis 1, 2.
• The absence of hydronephrosis on ultrasound makes larger ureteral stones (>5 mm) less likely, with ultrasound being up to 100% sensitive for hydronephrosis 3.

Renal Parenchymal Disease

• Trace proteinuria with flank pain may indicate early glomerular disease, interstitial nephritis, or thin basement membrane nephropathy 4, 5.
• However, significant proteinuria (>500 mg/24 hours or protein-to-creatinine ratio >0.2 g/g) would be expected for primary glomerular disease 1, 4.

Extraurinary Causes

• Right-sided flank pain: Consider right colonic diverticulitis, gastroenteritis, inflammatory bowel disease, or hepatobiliary pathology 1, 3.
• Left-sided flank pain: Consider splenic pathology, colonic diverticulitis, or pancreatic disease 1, 3.
• Women: Consider gynecologic causes including ovarian cysts, pelvic inflammatory disease, or ectopic pregnancy 3.

Recommended Diagnostic Workup

Immediate Laboratory Evaluation

• Serum creatinine and BUN to assess renal function 1.
• Complete metabolic panel including electrolytes, calcium, and uric acid 4.
• Spot urine protein-to-creatinine ratio to quantify proteinuria (normal <0.2 g/g) 4.
• Urine culture if any clinical suspicion of infection despite negative urinalysis 1, 8.

Imaging Strategy

• Non-contrast CT abdomen and pelvis is the gold standard with 98-100% sensitivity and specificity for detecting urinary stones AND identifies alternative diagnoses in approximately one-third of patients with flank pain 1, 3, 9.
• Renal ultrasound with Doppler is an appropriate alternative if radiation concerns exist or if initial evaluation suggests vascular compression syndromes like nutcracker syndrome 4, 3, 5.
• CT with IV contrast may be indicated if non-contrast CT is non-diagnostic and alternative intra-abdominal pathology is suspected 1.

When to Consider Nephrology Referral

• Persistent significant proteinuria (protein-to-creatinine ratio >0.2 g/g on repeat testing) 4.
• Elevated serum creatinine or declining renal function 1, 4.
• Development of hypertension in conjunction with flank pain and proteinuria 4, 7.

Treatment Approach Based on Diagnosis

If Musculoskeletal Cause Confirmed

• Conservative management with NSAIDs, physical therapy, and activity modification 3.
• Reassurance that symptoms are not kidney-related 3.

If Urolithiasis Identified

• Stones <5 mm typically pass spontaneously with conservative management including hydration and analgesia 3.
• Stones >5 mm or causing complete obstruction require urgent urology referral for consideration of intervention 3.
• Provide rapid analgesia (diclofenac intramuscular injection preferred) within 30 minutes 3.

If Nutcracker Syndrome Diagnosed

• Conservative management with observation for mild cases 5, 6.
• Surgical intervention (left renal vein transposition) for severe cases with significant symptoms 4.

If Page Kidney Identified

• Conservative management with antihypertensive therapy (ACE inhibitors preferred) for most cases 7.
• Evacuation of hematoma or nephrectomy reserved for refractory cases 7.

Critical Red Flags Requiring Urgent Evaluation

• Fever, chills, or signs of systemic infection mandate immediate evaluation for possible pyonephrosis or urosepsis 1, 3.
• Hemodynamic instability or shock requires urgent imaging and possible surgical intervention 3.
• Inability to urinate or decreased urine output suggests complete obstruction requiring urgent decompression 3.
• Palpable abdominal mass requires urgent ultrasound to exclude renal mass with inferior vena cava involvement 8.

Common Pitfalls to Avoid

• Do not assume absence of hematuria excludes urologic pathology—up to 20% of stone cases have negative urinalysis 1, 2.
• Do not anchor on nephrolithiasis when the clinical picture doesn't fit classic renal colic (colicky, wave-like, position-independent pain) 3, 7.
• Do not miss vascular compression syndromes like nutcracker syndrome when proteinuria and flank pain coexist without obvious cause 5, 6.
• Do not delay imaging in women of childbearing age—consider gynecologic emergencies including ectopic pregnancy 3.
• A normal urinalysis does not exclude significant urologic pathology and should not defer definitive imaging when clinical suspicion is high 3.