What are the initial urine laboratory tests for a patient suspected of having interstitial cystitis (IC) or lupus nephritis?

Initial Urine Laboratory Tests for Suspected Immune Checkpoint Inhibitor (ICI) Nephritis

For suspected ICI nephritis, obtain urinalysis with microscopy to assess for proteinuria, hematuria, and cellular casts (particularly white blood cell casts indicating interstitial inflammation), along with urine protein-to-creatinine ratio (UPCR) for quantification.

Essential Initial Urine Tests

Urinalysis with Microscopy

• Urinalysis with microscopic examination is the cornerstone initial test, evaluating for proteinuria, hematuria, pyuria, and most importantly, cellular casts 1
• White blood cell (WBC) casts are the hallmark finding in interstitial nephritis, suggesting pyelonephritis, interstitial nephritis, or inflammatory glomerular disease 1
• Granular casts indicate tubular damage and are formed from breakdown of cellular casts, which is relevant in ICI-related tubular injury 1
• The presence of pathological casts alongside proteinuria strongly suggests glomerular or tubulointerstitial disease requiring further evaluation 1

Urine Protein Quantification

• Spot urine protein-to-creatinine ratio (UPCR) should be obtained as it provides accurate quantification and can substitute for 24-hour urine collection 2
• A UPCR >0.5 (or >500 mg/g) is clinically significant and warrants further investigation 2
• Urine dipstick alone has limited sensitivity (56-80%) and specificity (67-92%) for detecting significant proteinuria and should not be relied upon as the sole measure 3

Urine Culture

• Urine culture should be obtained even with negative urinalysis to exclude infection, as lower levels of bacteria may be clinically significant but not detected on dipstick or microscopy 2
• This is particularly important since pyuria can occur in both infection and interstitial nephritis, and distinguishing between them is critical 1

Additional Considerations Based on Clinical Context

When Hematuria is Present

• If microscopic hematuria is present, particularly with a smoking history, urine cytology may be considered to exclude bladder malignancy, though this is more relevant in non-ICI contexts 2
• Red blood cell (RBC) casts indicate glomerular bleeding and suggest glomerulonephritis rather than pure interstitial nephritis 1

Comprehensive Microscopic Evaluation

• The microscopic examination should specifically document:
  • Number and types of casts per high-power field 1
  • RBCs (>5 RBC/hpf is considered significant) 2, 4
  • WBCs (>5 WBC/hpf in absence of infection is significant) 2, 4
  • Presence of epithelial/tubular casts indicating tubular damage 1

Common Pitfalls to Avoid

• Do not rely solely on urine dipstick results, as they correlate poorly with quantitative proteinuria and can miss significant disease 3
• Do not skip microscopic examination, as the presence and type of casts provide critical diagnostic information that cannot be obtained from automated urinalysis alone 1
• Do not assume negative urinalysis excludes significant kidney disease, particularly in early interstitial nephritis where findings may be subtle 2
• Waxy casts represent advanced tubular damage and chronic kidney disease, which would be unusual in acute ICI nephritis but important to recognize 1

Correlation with Serum Markers

• Urine findings should be interpreted alongside serum creatinine and estimated GFR to assess renal function 1
• Patients with pathological casts require monitoring of renal function, proteinuria, and blood pressure, with strong indication for nephrology referral, especially with declining renal function 1