Crystals and Elevated Epithelial Cells in Urine: Clinical Interpretation
The presence of crystals with epithelial cells >10/hpf in urine typically indicates either contamination from improper collection technique or increased cellular shedding from the urinary tract, with the clinical significance depending primarily on the type of crystals present and associated symptoms.
Understanding Epithelial Cells in Urine
Elevated epithelial cells (>10/hpf) most commonly represent specimen contamination rather than pathology. Normal urine contains some epithelial and blood cells from the urinary tract 1. However, when epithelial cell counts exceed 10 per high-powered field, this typically indicates:
- Contamination from periurethral flora during collection, particularly with bag specimens or inadequate clean-catch technique 1
- A urine sample with >10 WBCs and significant epithelial cells must be considered contaminated 1
- Proper collection via urethral catheterization (95% sensitivity, 99% specificity) or clean-catch with meticulous technique is essential to avoid false interpretation 1
The epithelial cells themselves originate from the nephron epithelial cells, urothelial cells lining the ureters and bladder, or urethral cells 1.
Clinical Significance of Crystalluria
Crystals in urine represent supersaturation with various substances and require identification of the specific crystal type to determine clinical significance 2, 3. The investigation must include:
- Fresh urine examination with polarized light microscopy 2, 4
- Urine pH measurement - critical for crystal identification 2, 4
- Crystal identification, quantification, and size measurement 2, 3
Common Crystal Types and Their Implications:
Calcium oxalate crystals are most frequently encountered and may indicate:
- Transient supersaturation (often benign) 4
- Risk for kidney stone formation requiring metabolic evaluation 5
- Primary hyperoxaluria when >200 pure whewellite crystals/mm³ are present, especially in children 5
Other significant crystals include calcium phosphates, uric acid, struvite, cystine, and drug-related crystals (sulfamethoxazole, amoxicillin, ceftriaxone, atazanavir) 2.
When to Pursue Further Evaluation
Metabolic evaluation is indicated for persistent crystalluria or stone history, including 24-hour urine collection analyzing volume, pH, calcium, oxalate, uric acid, citrate, sodium, potassium, and creatinine 5.
Nephrology referral should be considered for:
- Evidence of renal dysfunction or progressive decline 5
- Recurrent stone formation despite preventive measures 5
- Suspected inherited disorders (primary hyperoxaluria, cystinuria) 5
Urologic evaluation is indicated when:
- Hematuria accompanies crystalluria with risk factors for urologic disease 5
- Stones ≥5 mm unlikely to pass spontaneously 5
Management Approach
For patients with persistent crystalluria or stone history:
- Increase fluid intake to achieve urine volume ≥2.5 liters daily 5
- Dietary modifications based on crystal type:
- Repeat urinalysis with proper collection technique if contamination suspected 1
- Stone analysis if patient passes calculi 5
Critical Pitfalls to Avoid
- Do not interpret elevated epithelial cells as pathologic without considering collection technique - contamination is the most common cause 1
- Do not dismiss crystalluria as always benign - it can indicate serious metabolic disorders, inherited diseases, or drug toxicity 2, 4
- Do not analyze urine that has been standing - pH changes and temperature alterations after micturition cause artifact crystal formation 4
- Do not assume all crystals indicate stone disease - transient supersaturation from diet or urine concentration is common 4
The combination of crystals with high epithelial cells warrants repeat urinalysis with proper collection technique before pursuing extensive metabolic workup, unless clinical features suggest underlying pathology 1, 2.