Recurrent Acute Tubular Injury Associated with Alectinib in ALK-Positive Non-Small Cell Lung Cancer

Introduction: Alectinib, a second-generation ALK inhibitor, is widely used for ALK-positive non-small cell lung cancer (NSCLC). Nephrotoxicity, including acute tubular necrosis (ATN) and mixed interstitial nephritis–ATN patterns, has been increasingly reported. We describe a case of recurrent AKI temporally associated with Alectinib therapy. Case Description: A 70-year-old male with metastatic ALK-positive NSCLC was started on Alectinib in November 2024, with a baseline creatinine of 0.8–1.0 mg/dL. Three weeks later, he developed AKI with a peak creatinine of 3.78 mg/dL. Alectinib was held, and renal function rapidly improved to baseline. Therapy was resumed within two weeks, and creatinine remained stable for two months. In February 2025, he re-presented with chest pain and generalized weakness. Creatinine was 2.66 mg/dL with bland urine sediment and 20 mg/dL proteinuria. Renal ultrasound was unremarkable. Alectinib was again discontinued, with subsequent improvement in kidney function. Given the timing and recurrence with drug re-challenge, Alectinib-induced nephrotoxicity was the most likely culprit. Discussion: Alectinib has been implicated in tubular injury in emerging reports. Proposed mechanisms include direct tubular toxicity and transporter-mediated accumulation via OCT2 and MATE1 inhibition. Although biopsy was not pursued, the reversible AKI pattern, absence of confounders, and recurrence with re-exposure support Alectinib-induced ATN. Prior reports describe ATN and mixed AIN–ATN lesions. Recognition of Alectinib-induced renal injury is crucial given reversibility.Serum Creatinine Trend Over Time in Relation to Alectinib Therapy