From the Guidelines
Pembrolizumab-induced acute kidney injury (AKI) should be managed by temporarily discontinuing the medication and initiating corticosteroid therapy, typically with prednisone 1-2 mg/kg/day, as supported by the American Society of Clinical Oncology clinical practice guideline 1. When pembrolizumab-induced AKI is suspected, it is essential to obtain a nephrology consultation promptly. The diagnosis is supported by new-onset kidney dysfunction, urinalysis showing pyuria and/or hematuria, and sometimes eosinophilia. Key considerations in managing pembrolizumab-induced AKI include:
- Temporarily discontinuing pembrolizumab to prevent further kidney damage
- Initiating corticosteroid therapy to reduce inflammation
- Monitoring kidney function closely during treatment
- Considering additional immunosuppressants in severe or steroid-resistant cases The mechanism of pembrolizumab-induced AKI involves T-cell mediated inflammation of the kidney interstitium triggered by immune checkpoint inhibition, as noted in a study published in the Journal of Clinical Oncology 1. Pembrolizumab-induced AKI typically occurs within 3-12 months of starting therapy, though it can develop earlier or later, highlighting the importance of regular monitoring of renal function, as recommended by Brahmer et al. 1. Early recognition and treatment are crucial for preserving kidney function and determining whether pembrolizumab can be safely resumed after resolution.
From the Research
Pembrolizumab-Induced Acute Kidney Injury (AKI)
- Pembrolizumab, an anti-programmed cell death 1 (PD-1) agent, has been associated with renal toxicities, including AKI 2.
- A study found that the incidence of pembrolizumab-induced AKI was 1.77% in a cohort of 676 patients 2.
- The most common forms of kidney involvement under pembrolizumab therapy are acute tubular injury (ATI), acute interstitial nephritis (AIN), and minimal change disease (MCD) 2, 3.
- Pembrolizumab withdrawal coupled with corticosteroid therapy is often effective in treating kidney function recovery 2, 3.
- However, drug reintroduction can result in a more severe recurrence of AIN in some patients 2.
Clinical Presentation and Diagnosis
- Patients with pembrolizumab-induced AKI may present with acute onset of nephrotic syndrome, oliguria, and pulmonary congestion 3.
- Renal biopsy is essential in diagnosing the underlying cause of AKI, but it may not always be possible due to anticoagulation therapy or other contraindications 3, 4.
- Immunohistochemical evaluation of renal biopsy using anti-PD1 and p53 markers may help identify the drug responsible for renal damage in patients receiving combination therapy with platinum and pembrolizumab 5.
Treatment and Management
- Discontinuation of pembrolizumab and initiation of corticosteroid therapy are often necessary to manage pembrolizumab-induced AKI 2, 3, 4.
- Hemodialysis may be required in severe cases of AKI, but renal function can be reversible with prednisolone therapy 3.
- Early identification of increased serum creatinine levels is crucial in preventing further kidney damage and improving treatment outcomes 4.
Rare but Serious Adverse Effects
- Pembrolizumab-induced AKI can occur simultaneously with other immune-related adverse effects, such as acute liver injury (ALI) 6.
- The mechanism of these adverse effects is poorly understood, and further research is needed to characterize their presentation and facilitate earlier recognition and intervention 6.