What is the appropriate management for a patient with squamous epithelial and hyaline casts in their urine?

Management of Squamous Epithelial Cells and Hyaline Casts in Urine

The presence of squamous epithelial cells in urine typically indicates specimen contamination and warrants recollection using proper technique, while hyaline casts ≥100/whole field suggest underlying kidney disease requiring evaluation of kidney function and proteinuria. 1, 2

Squamous Epithelial Cells: Interpretation and Action

Normal Origin and Contamination

• Squamous epithelial cells normally originate from the distal urethra, bladder trigone, or cervicovaginal region in women 1
• When significant squamous cells appear alongside >10 WBCs or mixed bacterial flora, this strongly suggests specimen contamination rather than true pathology 1

Recollection Strategy

• If clinical suspicion for urinary tract infection or other pathology remains high despite contamination, obtain a catheterized specimen 1
• Clean-catch specimens have 27% contamination rates versus only 4.7% for catheterized specimens 1
• Proper perineal cleansing before collection reduces contamination from 23.9% to 7.8% 1
• Catheterization provides 95% sensitivity and 99% specificity for accurate results 1

When Squamous Cells Indicate Pathology

Atypical squamous cells (ASCs) with large hyperchromatic nuclei, high nuclear-to-cytoplasmic ratio, or abnormal shapes require aggressive workup 3:

• 25% of patients with urinary ASCs are subsequently diagnosed with squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation 3
• 6% have high-grade cervical squamous cell carcinoma 3
• Perform cystoscopy with biopsy for any atypical squamous cells 3
• Women with urinary ASCs require pelvic examination to exclude cervical malignancy 3, 4

Hyaline Casts: Clinical Significance

Threshold for Concern

Hyaline casts ≥100/whole field indicate high-risk chronic kidney disease and warrant immediate evaluation 2:

• This threshold has 44.7% sensitivity and 96.5% specificity for identifying high-risk CKD 2
• Patients with ≥100 hyaline casts/whole field have significantly lower eGFR values, particularly those with hypertension 2

Composition and Formation Mechanism

• Hyaline casts consist primarily of Tamm-Horsfall mucoprotein with small amounts of serum proteins 5
• Cast formation invariably associates with significant proteinuria—serum albumin precipitates Tamm-Horsfall protein to form casts 5

Required Workup for Significant Hyaline Casts

When ≥100 hyaline casts/whole field are present, immediately obtain 6, 2:

• Serum creatinine and calculate eGFR using the 2021 CKD-EPI equation (without race factor) 6
• Spot urine protein-to-creatinine ratio (UPCR), preferably first morning sample 6
• Serum albumin level 6
• Urinalysis with microscopic examination for dysmorphic RBCs, RBC casts, and WBC casts 6
• Blood pressure measurement 6

Risk Stratification

• Categorize CKD risk using KDIGO 2009 classification based on eGFR and albuminuria 2
• Patients with ≥100 hyaline casts/whole field typically fall into risk group 3 or higher, requiring nephrology referral 2
• Even patients with normal albuminuria (A1 stage) but 100-999 or ≥1,000 hyaline casts/whole field have significantly reduced eGFR 2

Common Pitfalls to Avoid

• Do not treat presumed UTI based on urinalysis showing squamous cells and bacteria without proper specimen recollection 1
• Do not dismiss atypical squamous cells as contamination—31% represent malignancy 3
• Do not overlook hyaline casts as "benign"—they indicate proteinuria and kidney disease when present in significant numbers 2, 5
• Do not use race-based eGFR equations; use 2021 CKD-EPI creatinine equation 6
• Do not rely on automated urinalysis alone; direct microscopic examination by trained personnel is essential for accurate cast identification 6