Pembrolizumab-Induced AKI

Introduction: Pembrolizumab, a monoclonal antibody targeting the programmed death 1 (PD-1) receptor, has revolutionized cancer therapy by enhancing T-cell-mediated anti-tumor immune responses. Despite its efficacy, Pembrolizumab is associated with immune-related adverse events (irAEs), including acute kidney injury (AKI), a rare but serious complication. Case Description: An 86-year-old female with hypertension and type 2 diabetes mellitus was diagnosed with stage IV squamous cell lung cancer and initiated Pembrolizumab treatment. Within weeks, her renal function deteriorated, evidenced by declining glomerular filtration rate and rising creatinine levels. Pembrolizumab was discontinued after the second cycle due to significant creatinine elevation. Despite kidney protective measures, renal function did not improve. Urinalysis revealed an elevated urine protein/creatinine ratio, suggestive of AIN. Treatment with slow prednisone taper led to gradual improvement, with creatinine normalization and establishment of a new baseline glomerular filtration rate. Discussion: The incidence of immune checkpoint-induced acute kidney injury (ICI-AKI) is estimated to range between 2-3%. Acute interstitial nephritis (ATIN) is the most common pathology in this context. Diagnosis is challenging due to multiple AKI risk factors in cancer patients. Clinical features such as sterile pyuria, white blood cell casts, and sub-nephrotic range proteinuria, commonly associated with ICPI-AKI, lack sensitivity and specificity and may manifest in other causes of ATIN. Increased vulnerability to ICPI-AKI is observed in patients experiencing other immune-related adverse effects (irAEs) linked to ICIs and PPIs. Current guidelines recommend initiating empirical treatment for ICPI-AKI without awaiting tissue diagnosis unless a three-fold increase in creatinine or suspicion of alternative causes for AKI arises. Prednisone, coupled with the discontinuation of the immune checkpoint inhibitor, constitutes the recommended therapeutic approach in the management of ICPI-AKI.