Laboratory Evaluation for Immune Checkpoint Inhibitor (ICI) Nephritis
For suspected ICI nephritis, monitor serum creatinine before every dose and obtain urinalysis when creatinine rises ≥50% above baseline, along with assessment for alternative causes including recent IV contrast, nephrotoxic medications, and urinary tract infection. 1
Essential Baseline and Monitoring Labs
Serum Chemistry Panel
- Serum creatinine is the primary monitoring parameter and should be checked before every ICI dose 1
- Sustained increase in serum creatinine ≥50% on at least two consecutive values defines probable ICI-related nephritis 1
- Electrolytes including potassium should be repeated every 48 hours for Grade 2 nephritis and every 24 hours for Grade 3 1
- Blood urea nitrogen (BUN) to assess BUN:creatinine ratio, which helps distinguish prerenal from intrinsic causes 2
Urinalysis Components
- Dipstick urinalysis for leukocyte esterase, nitrite, protein, and specific gravity 1
- Microscopic examination for white blood cells (WBCs), with sterile pyuria (≥5 WBCs/hpf) supporting the diagnosis of ICI nephritis 1
- Urine protein assessment via spot urine protein-to-creatinine ratio (UPCR) or 24-hour collection if proteinuria is present 1
- Phase contrast microscopy if hematuria is present to evaluate for glomerular disease 1
Additional Diagnostic Studies When Indicated
For Grade 2 or higher nephritis with no clear alternative cause:
- Renal ultrasound with Doppler to exclude obstruction, clot, or structural abnormalities 1
- Glomerulonephritis screen including ANA, complement C3/C4, ANCA, anti-GBM antibodies 1
- Hepatitis B and C serologies, HIV testing 1
- Serum immunoglobulins and protein electrophoresis to evaluate for monoclonal gammopathy 1
Diagnostic Algorithm
Grade 1 (Creatinine 1.5-2.0× baseline or >0.3 mg/dL increase)
- Repeat creatinine weekly 1
- Obtain urinalysis to rule out UTI and assess for pyuria 1
- Review hydration status and all medications including over-the-counter agents, herbals, and recent contrast exposure 1
- Consider temporarily holding ICI pending evaluation of alternative etiologies 1
Grade 2 (Creatinine 2-3× baseline)
- Hold ICI temporarily 1
- Consult nephrology 1
- Repeat creatinine and potassium every 48 hours 1
- Obtain renal ultrasound with Doppler if obstruction suspected 1
- If attributed to ICI after excluding alternatives, initiate corticosteroids 1
Grade 3-4 (Creatinine ≥3× baseline or ≥4.0 mg/dL)
- Permanently discontinue ICI if directly implicated 1
- Admit patient for monitoring and fluid balance 1
- Repeat creatinine every 24 hours 1
- Early nephrology consultation for potential biopsy 1
- Initiate IV methylprednisolone 1-2 mg/kg/day if worsening 1
Critical Diagnostic Considerations
Routine urinalysis is NOT necessary for asymptomatic patients receiving ICIs—testing should be reserved for those with elevated creatinine or symptoms suggesting renal involvement 1
Kidney biopsy should be discouraged until steroid treatment has been attempted unless there is diagnostic uncertainty or failure to improve with steroids 1. However, early consideration for biopsy is helpful to determine whether deterioration is ICI-related or due to other pathology 1.
The absence of an alternative plausible etiology combined with sustained creatinine elevation and sterile pyuria or eosinophilia (≥500 cells/mL) establishes probable ICI-related nephritis without requiring biopsy 1.
Common Pitfalls to Avoid
- Do not assume all creatinine elevations are ICI-related—systematically exclude dehydration, recent IV contrast (within 48-72 hours), nephrotoxic medications, UTI, and hypotension before attributing to immunotherapy 1
- Baseline renal function matters more than absolute values—a creatinine of 1.5 mg/dL may represent Grade 3 toxicity if baseline was 0.5 mg/dL 1
- Eosinophilia and sterile pyuria are supportive but not required for diagnosis—their absence does not exclude ICI nephritis 1
- Swift treatment of the autoimmune component is important once alternative causes are excluded 1