What does the presence of epithelial cells in urine indicate?

Epithelial Cells in Urine: Clinical Significance

The presence of epithelial cells in urine primarily indicates specimen contamination rather than disease, with squamous epithelial cells signaling contamination from the distal urethra or genitourinary tract, while renal tubular epithelial cells (RTECs) may indicate actual upper urinary tract pathology. 1

Types of Epithelial Cells and Their Meaning

Squamous Epithelial Cells

• Originate from the distal urethra, bladder trigone, or cervicovaginal contamination during collection and represent the most common type seen in routine urinalysis. 1, 2
• Their abundant presence (>10 cells per field) alongside mixed bacterial flora indicates specimen contamination, not infection, and necessitates recollection using a more reliable method if clinical suspicion for UTI remains high. 1, 2
• These cells are the primary marker of improper collection technique rather than pathology. 1

Transitional (Urothelial) Epithelial Cells

• Arise from the urinary tract lining (renal pelvis, ureters, bladder) and when appearing atypical, may indicate urothelial neoplasia requiring cytologic evaluation. 1, 3
• The International Consultation on Urologic Disease (ICUD) recommends standardized reporting using terminology similar to the Bethesda System, with atypical cells substratified into two classes: atypical urothelial cells of undetermined significance versus those that cannot rule out high-grade carcinoma. 1, 4

Renal Tubular Epithelial Cells (RTECs)

• Contain nephron-specific proteins and indicate upper urinary tract pathology, distinguishing them from contamination markers. 1, 4
• RTECs demonstrate acceptable diagnostic performance for upper UTI diagnosis and help discriminate between upper and lower urinary tract infections. 5
• In diabetic nephropathy patients, the presence of RTECs or RTEC casts correlates with more severe kidney injury (higher proteinuria, elevated serum creatinine, lower eGFR) and independently predicts progression to end-stage kidney disease. 6
• RTECs can be cultured from urine and serve as valuable models for studying genetic kidney diseases, with diabetic patients with advanced nephropathy exfoliating significantly higher numbers (50.8 cells/100 ml urine versus 5.2 cells/100 ml in those without nephropathy). 7, 8

Impact of Collection Method on Contamination

Collection technique dramatically affects contamination rates and specimen reliability:

• Catheterized specimens: 4.7% contamination rate with 95% sensitivity and 99% specificity. 1, 2
• Clean-catch midstream: 27% contamination rate. 1, 2
• Bag specimens: 65-68% contamination rate. 1, 2
• Proper perineal cleansing reduces contamination from 23.9% to 7.8%. 1, 2

Clinical Decision Algorithm

When Interpreting Epithelial Cells in Urine:

1. Assess the collection method first - bag specimens are unreliable, catheterization provides the most accurate results. 1, 2

2. Quantify squamous epithelial cells:

   • If >10 cells per field with mixed bacterial flora → specimen contaminated, recollect via catheterization if clinical suspicion for UTI persists. 1, 2
   • In children with fever and suspected UTI, confirm any positive culture showing mixed flora and squamous cells by catheterization or suprapubic aspiration before initiating treatment. 1, 2

3. Evaluate RTECs specifically:

   • Presence suggests upper urinary tract pathology (pyelonephritis, acute tubular injury, diabetic nephropathy). 1, 6, 5
   • In diabetic patients, RTECs or RTEC casts predict worse renal outcomes and ESKD development. 6

4. Assess atypical transitional cells:

   • Require formal cytologic evaluation using standardized reporting systems to rule out urothelial carcinoma. 1, 4

Emerging Diagnostic Applications

• Urinary extracellular vesicles (EVs) derived from epithelial cells represent a frontier in biomarker discovery, containing proteins from specific nephron segments (podocin from podocytes, megalin from proximal tubules, uromodulin from Henle's loop). 4
• These EVs enable detection of low-concentration proteins not previously identifiable in bulk urine and provide noninvasive windows into kidney pathophysiology. 4
• Advanced techniques like urinary flow cytometry and single-cell sequencing of epithelial cells may guide treatment decisions and potentially substitute for biopsy in selected cases. 4