From the Guidelines
The diagnostic approach for pembrolizumab-induced nephritis involves prompt recognition through laboratory monitoring and kidney biopsy when indicated, with a focus on grading the severity of nephritis based on creatinine elevation, as outlined in the 2021 ASCO guideline update 1. The diagnostic process should include regular monitoring of serum creatinine and urinalysis before each pembrolizumab dose, with increased vigilance during the first 3-6 months of therapy when most cases occur. When nephritis is suspected based on rising creatinine (typically a 1.5-fold increase from baseline), a comprehensive workup should include:
- Urinalysis with microscopy
- Urine protein-to-creatinine ratio
- Complete blood count
- Comprehensive metabolic panel Other causes of acute kidney injury should be excluded, including pre-renal causes, obstruction, and other nephrotoxic medications. A kidney biopsy is often necessary to confirm the diagnosis and typically shows acute tubulointerstitial nephritis with lymphocytic infiltration, as noted in a retrospective series of patients who underwent kidney biopsy after developing renal toxicity from checkpoint inhibitor immunotherapy 1. Renal ultrasound may be performed to rule out obstruction. The severity of nephritis is graded from 1-4 based on creatinine elevation, with management decisions guided by this grading, as outlined in the 2021 ASCO guideline update 1. Early recognition is critical as pembrolizumab-induced nephritis can progress rapidly but often responds well to immunosuppressive therapy and drug discontinuation when identified promptly. It is also important to consider the potential for other causes of renal toxicity, such as recent IV contrast administration, dehydration, other medicines, and urinary tract infection, and to evaluate and treat these potential causes accordingly, as recommended in the 2018 American Society of Clinical Oncology clinical practice guideline 1.
From the Research
Diagnostic Approach for Pembrolizumab (Keytruda) Induced Nephritis
The diagnostic approach for pembrolizumab-induced nephritis involves several steps, including:
- Clinical evaluation: Patients presenting with acute kidney injury (AKI) and/or proteinuria after pembrolizumab treatment should be evaluated for potential nephritis 2, 3, 4, 5, 6.
- Laboratory tests: Serum creatinine levels, urine analysis, and other laboratory tests can help identify kidney dysfunction and guide further diagnosis 2, 5.
- Kidney biopsy: A kidney biopsy can be performed to determine the underlying cause of nephritis, such as acute interstitial nephritis (AIN), acute tubular injury (ATI), or minimal change disease (MCD) 2, 3, 4.
- Imaging studies: Imaging studies, such as ultrasound or CT scans, may be used to evaluate kidney structure and function 2, 6.
Key Findings and Considerations
- Pembrolizumab-induced nephritis can manifest as AIN, ATI, or MCD, with AIN being the most common form 2, 5.
- The incidence of pembrolizumab-induced nephritis is estimated to be around 1.77% 2.
- Corticosteroid therapy is often effective in treating pembrolizumab-induced nephritis, particularly AIN 2, 5, 6.
- Discontinuation of pembrolizumab may be necessary in some cases, especially if kidney function does not recover with treatment 5, 6.
- Combining immune checkpoint inhibitors with chemotherapy requires careful consideration of potential concurrent drug-induced nephrotoxicity 3.