What are the differential diagnoses and appropriate management for a 30‑year‑old woman presenting with gross hematuria, right flank pain, dysuria, a single episode of vomiting, and a negative urine dipstick for nitrites?

Differential Diagnosis and Management for 30-Year-Old Female with Hematuria, Right Flank Pain, Dysuria, and Vomiting

This patient requires urgent urologic evaluation with imaging (CT urography) and urology referral, as gross hematuria carries a 30-40% risk of malignancy even in young patients, and the combination of flank pain with hematuria strongly suggests urolithiasis or upper tract pathology that demands immediate assessment. 1, 2

Immediate Diagnostic Steps

Confirm true hematuria by obtaining microscopic urinalysis showing ≥3 RBCs per high-power field on a properly collected clean-catch midstream specimen, as dipstick testing alone has only 65-99% specificity and can produce false positives. 1, 2

Obtain urine culture before initiating antibiotics to document whether infection is present, as pyuria does not exclude concurrent malignancy and infection may mask underlying pathology. 2, 3

Measure serum creatinine to assess renal function and identify potential obstruction or acute kidney injury. 2, 4

Differential Diagnosis (Ranked by Likelihood)

1. Urolithiasis (Most Likely)

• Classic triad: flank pain + hematuria + vomiting suggests renal colic 4, 5
• Right-sided location points to right ureteral or renal stone 6
• Note: 14.5% of patients with acute urinary lithiasis have negative microscopic hematuria on urinalysis alone, but only 5.5% are negative when both urinalysis and dipstick are combined 5
• Negative nitrites do not rule out stones 1

2. Urinary Tract Infection (Pyelonephritis)

• Dysuria + flank pain + vomiting can indicate upper tract infection 3, 7
• However, negative nitrites make UTI less likely (nitrites have high specificity for infection, particularly when positive) 3, 8
• Nitrite sensitivity is only ~53% in pediatric studies but specificity is ~98%, so a negative result does not exclude infection 2
• Pyuria is commonly found without infection, especially with lower urinary tract symptoms 3, 7

3. Urologic Malignancy (Must Not Miss)

• Gross hematuria in any adult warrants urgent evaluation due to 30-40% malignancy risk 1, 2
• Risk factors to assess: smoking history (>30 pack-years = high risk), occupational exposure to benzenes/aromatic amines, family history 2, 4
• Bladder cancer is most common malignancy in hematuria cases, but upper tract urothelial carcinoma and renal cell carcinoma must be excluded 2, 4

4. Glomerular Disease (Less Likely but Important)

• Assess for tea-colored or cola-colored urine (suggests glomerular source) 2, 4
• Examine urinary sediment for dysmorphic RBCs (>80% indicates glomerular origin) and red cell casts (pathognomonic for glomerulonephritis) 2, 4
• Check spot urine protein-to-creatinine ratio; values >0.5 g/g strongly suggest renal parenchymal disease 2
• IgA nephropathy and post-infectious glomerulonephritis are common glomerular causes in young adults 2, 4

5. Renal Trauma

• Inquire about recent trauma, vigorous exercise, or sexual activity 2, 4
• Even minor trauma to an anomalous kidney can cause significant hematuria 2

Management Algorithm

Step 1: Immediate Laboratory Evaluation

• Microscopic urinalysis with examination for dysmorphic RBCs, red cell casts, crystals 2, 7
• Urine culture (obtain before antibiotics) 2, 3
• Serum creatinine and complete metabolic panel 2, 4
• Spot urine protein-to-creatinine ratio 2
• Complete blood count to assess for anemia or infection 2

Step 2: Risk Stratification for Imaging

Proceed immediately to multiphasic CT urography (unenhanced, nephrographic, and excretory phases) because: 2, 4

• Gross hematuria = automatic high-risk regardless of age 1, 2
• Flank pain + hematuria = classic presentation requiring stone/mass exclusion 4, 5
• CT urography is 96% sensitive and 99% specific for urothelial malignancy 2
• Detects stones, masses, obstruction, and anatomic abnormalities in a single study 2, 4

Alternative imaging (only if CT contraindicated due to pregnancy, severe renal insufficiency, or contrast allergy): 2

• MR urography or renal ultrasound with retrograde pyelography 2

Step 3: Antibiotic Decision

Do NOT prescribe empiric antibiotics if:

• Urinalysis shows negative nitrite AND negative leukocyte esterase 1
• Patient lacks fever, rigors, or systemic symptoms 1
• Await urine culture results 2, 3

Consider empiric antibiotics if:

• Fever >37.8°C, rigors, or signs of sepsis are present 1
• Significant pyuria (>8 WBC/hpf on manual microscopy or >10 WBC/mm³ on hemocytometer) 7
• Choose: nitrofurantoin, fosfomycin, or trimethoprim-sulfamethoxazole (if local resistance <20%) 3
• For suspected pyelonephritis: fluoroquinolone or ceftriaxone 3

Critical caveat: If hematuria persists after treating infection, proceed immediately with full urologic evaluation, as infection does not explain persistent hematuria and may mask malignancy. 2, 3

Step 4: Urgent Urology Referral

Refer to urology within 24-48 hours for cystoscopy because: 1, 2

• All adults with gross hematuria require cystoscopy, even if self-limited 1, 2
• Flexible cystoscopy is preferred (less pain, equivalent diagnostic accuracy) 2, 4
• Imaging alone is insufficient—bladder cancer requires direct visualization 2

Step 5: Nephrology Referral (If Indicated)

Refer to nephrology if any of the following are present: 2, 4

• Dysmorphic RBCs >80% or red cell casts on microscopy 2, 4
• Protein-to-creatinine ratio >0.5 g/g 2
• Elevated serum creatinine or declining renal function 2
• Hypertension accompanying hematuria and proteinuria 2

Note: Glomerular features do not eliminate the need for urologic evaluation—both evaluations should be completed, as malignancy can coexist with medical renal disease. 2

Common Pitfalls to Avoid

Never ignore gross hematuria, even if self-limited or a benign cause is suspected—30-40% malignancy risk mandates urgent evaluation. 1, 2

Do not attribute hematuria to UTI alone without confirming infection resolves the hematuria; repeat urinalysis 6 weeks after treatment, and if hematuria persists, proceed with full urologic workup. 2, 3

Do not delay evaluation waiting for "infection to clear"—obtain imaging and urology referral concurrently with infection treatment. 2

Negative nitrites do not rule out UTI (sensitivity only ~53%), but they make infection less likely and should prompt consideration of alternative diagnoses. 2, 3

Do not assume young age excludes malignancy—while risk increases with age, bladder cancer and upper tract tumors occur in patients <40 years, especially with risk factors. 2, 4

Follow-Up Protocol

If initial workup is negative but hematuria persists: 2

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring 2
• Immediate re-evaluation if gross hematuria recurs, microscopic hematuria increases significantly, new urologic symptoms develop, or hypertension/proteinuria/glomerular bleeding emerges 2

If urolithiasis is confirmed: 4, 5

• Manage stone per size and location (medical expulsive therapy vs. intervention) 4
• Metabolic workup (24-hour urine collection) for recurrent stone formers 2

If infection is confirmed and treated: 3

• Repeat urinalysis 6 weeks post-treatment 2
• If hematuria resolves, no further urologic workup needed in low-risk patients 2
• If hematuria persists, proceed with CT urography and cystoscopy 2