Are granular or waxy casts considered cellular casts?

Are Granular or Waxy Casts Considered Cellular Casts?

Yes, granular casts are explicitly classified as cellular casts in the American College of Rheumatology criteria for lupus nephritis, while waxy casts are not considered cellular casts but rather represent a distinct category of pathological casts indicating advanced tubular damage. 1

Classification According to ACR Guidelines

The American College of Rheumatology defines cellular casts to include:

• Red blood cell casts
• Hemoglobin casts
• Granular casts (explicitly listed as cellular)
• Tubular (epithelial) casts
• Mixed casts 1

Waxy casts are notably absent from this list of cellular casts, indicating they represent a separate pathological entity. 1

Updated ACR Criteria Clarification

The revised ACR criteria further refined the definition of "active urinary sediment" to include:

• Greater than 5 RBC/hpf
• Greater than 5 WBC/hpf (in absence of infection)
• Cellular casts specifically limited to RBC or WBC casts only 1

This revision suggests a more restrictive interpretation where only RBC and WBC casts qualify as "cellular casts" in the strictest sense for diagnostic purposes, though granular casts remain included in the broader ACR classification criteria. 1

Clinical Significance and Pathophysiology

Granular Casts

• Formed from the breakdown and degeneration of cellular casts (particularly epithelial cells), representing tubular damage 2
• Indicate active tubular injury and are considered pathological 2
• Found in various glomerular diseases and associated with renal dysfunction 3

Waxy Casts

• Represent the final stage of cast degeneration and indicate advanced, chronic tubular damage 2
• Associated with chronic kidney disease and severe renal impairment 2
• Strongly correlated with higher serum creatinine levels (p<0.0001) and impaired renal function 3
• Detection rate of 26.3% in patients undergoing renal biopsy, with high specificity (0.97) but low sensitivity (0.29) for renal insufficiency (eGFR <60 mL/min/1.73 m²) 4

Practical Clinical Algorithm

When evaluating urinary casts:

1. Identify cast type under microscopy using Sternheimer-Malbin staining 5

2. Classify as cellular casts if:

   • Red blood cell casts (diagnostic of glomerulonephritis) 2
   • White blood cell casts (suggest pyelonephritis or interstitial nephritis) 2
   • Granular casts (indicate tubular damage from cellular breakdown) 2
   • Epithelial/tubular casts 1

3. Classify as non-cellular pathological casts if:

   • Waxy casts (indicate advanced chronic kidney disease) 2
   • Fatty casts (associated with nephrotic syndrome) 2
   • Hyaline casts (may be benign or pathological depending on context) 6

Common Pitfalls to Avoid

• Do not assume all pathological casts are cellular casts—waxy casts are pathological but represent a distinct category indicating chronicity rather than active cellular injury 2, 3
• Waxy casts are frequently found alongside other pathological findings including leukocytes, granular casts, and leukocytic casts (p=0.001 to 0.008), so their presence should prompt comprehensive evaluation 3
• The presence of waxy casts indicates more advanced disease with greater glomerular obsolescence (46% vs 20%, p=0.003) and should trigger nephrology referral 7, 4
• Granular casts may progress to waxy casts over time as they undergo further degeneration in the tubules, representing a continuum of tubular pathology 8