What could be the cause of dysuria, incontinence, and frequency of urination in a 5-year-old girl with a urinalysis showing hematuria (blood in urine), proteinuria (protein in urine), and normal specific gravity (S.G.), but negative for nitrite and leukocyte esterase?

Likely Diagnosis: Cystitis (Lower Urinary Tract Infection)

The most likely cause of dysuria, urinary frequency, and incontinence in this 5-year-old girl with hematuria and proteinuria but negative nitrite and leukocyte esterase is cystitis (bladder infection), though the negative inflammatory markers make this diagnosis less straightforward and warrant careful clinical correlation.

Understanding the Urinalysis Findings

The urinalysis shows several important features that guide diagnosis:

• Small blood (1+) with negative nitrite and leukocyte esterase creates a diagnostic challenge, as typical bacterial UTI usually shows pyuria (positive leukocyte esterase) 1
• The combination of negative leukocyte esterase and negative nitrite has 90.5% negative predictive value for UTI in most populations, though this applies primarily to adults 2
• Proteinuria (1+ or 30 mg/dL) combined with hematuria can occur in cystitis but also raises concern for glomerular causes 3, 4
• Normal specific gravity (1.030) indicates adequate hydration and normal concentrating ability 1

Primary Differential Diagnosis

Most Likely: Cystitis Despite Negative Markers

Cystitis typically presents with dysuria, frequency, and urgency in children, and the classic triad of symptoms strongly suggests lower urinary tract infection 1

However, several important caveats apply:

• In children, 10-50% of culture-proven UTIs have false-negative urinalysis, making urine culture mandatory regardless of dipstick results 2, 5
• Leukocyte esterase has only 84-94% sensitivity in pediatric patients, meaning significant false-negative rates occur 2
• Nitrite testing has particularly poor sensitivity (19-48%) in children who void frequently, as shorter bladder dwell time prevents adequate nitrate-to-nitrite conversion 2
• The absence of pyuria does NOT exclude UTI in children, especially when classic symptoms are present 6, 5

Alternative Considerations

Chemical or mechanical bladder irritation could explain dysuria that improves with hydration, though persistent symptoms regardless of fluid intake favor infection 7

Viral cystitis can present with hematuria and dysuria but typically shows some pyuria 8

Early glomerulonephritis must be considered given the combination of hematuria and proteinuria, though the absence of tea-colored urine, normal blood pressure (if checked), and predominant lower urinary symptoms make this less likely 3, 4

Critical Next Steps

Mandatory Immediate Actions

Obtain urine culture via catheterization or suprapubic aspiration before any antibiotic therapy, as this is the gold standard for diagnosing UTI in young children and bag-collected specimens have only 15% positive predictive value 2, 5

Assess for systemic signs of pyelonephritis including fever >38.3°C, flank pain, vomiting, or appearing ill, as these would indicate upper tract involvement requiring more aggressive treatment 1, 5

Examine for vulvovaginitis or other local causes of dysuria, as vaginal discharge or perineal irritation can mimic UTI symptoms 7, 8

Diagnostic Algorithm

1. If fever or systemic symptoms present: Treat as febrile UTI with 7-10 days of antibiotics after obtaining culture, and plan renal/bladder ultrasound for children <2 years or after first febrile UTI in older children 1, 5

2. If afebrile with isolated lower urinary symptoms: Obtain culture and consider empiric treatment with nitrofurantoin or first-generation cephalosporin for 3-5 days pending culture results 2, 5

3. If culture is negative despite symptoms: Investigate non-infectious causes including chemical irritants, hypercalciuria, or early interstitial cystitis 3, 8

4. If proteinuria persists after infection resolves: Obtain spot urine protein-to-creatinine ratio and consider nephrology referral if >0.2 g/g, as persistent proteinuria may indicate glomerular disease 4

Common Pitfalls to Avoid

Never dismiss UTI based solely on negative dipstick in a symptomatic child, as up to 50% of culture-proven UTIs have negative urinalysis in pediatric patients 2, 5

Do not use bagged urine specimens for culture, as contamination rates are unacceptably high and lead to false-positive results and unnecessary antibiotic exposure 5

Avoid attributing all dysuria to UTI without considering vulvovaginitis, pinworms, or sexual abuse, especially in toilet-trained children with new-onset incontinence 1, 8

Do not defer imaging after first febrile UTI in children <2 years, as early detection of anatomic abnormalities is critical to prevent renal scarring 1, 6, 5

Treatment Considerations

If empiric treatment is initiated pending culture, use nitrofurantoin 5-7 mg/kg/day divided twice daily or cephalexin 50-100 mg/kg/day divided 3-4 times daily for 3-5 days for uncomplicated cystitis 2, 5

Adjust therapy based on culture results and clinical response within 48-72 hours, and consider imaging if symptoms persist despite appropriate antibiotics 1, 5

Reassess for constipation and voiding dysfunction, as these are major risk factors for recurrent UTI in toilet-trained children and require behavioral interventions 6