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Case Description A 43-year-old man with metastatic epithelioid sarcoma was initially treated with ifosfamide and doxorubicin, leading to Fanconi syndrome characterized by phosphate wasting, glucosuria, and metabolic acidosis. Kidney function stabilized (creatinine 0.8 mg/dl) after stopping ifosfamide. Following disease progression, tazemetostat was started. Eight months into therapy, the serum creatinine rose to 2.04 mg/dl, and a 24-hour urine collection showed 3.25 g/d proteinuria. Workup for autoimmune, viral, and paraprotein-related kidney diseases was negative. Kidney biopsy was performed. Biopsy revealed chronic lymphocytic tubulointerstitial nephritis with eosinophils, severe proximal tubular injury, and 80% cortical fibrosis and atrophy. Glomeruli were unremarkable on light, immunofluorescence, and electron microscopy. No light chains or crystals were identified, excluding light chain proximal tubulopathy. Tazemetostat was discontinued, and prednisone (60 mg daily) was initiated. With little improvement, mycophenolate mofetil (500mg twice a day)was added 6weeks later but caused anemia requiring dose reduction. The patient progressed to ESKD and began maintenance hemodialysis. Image Description Hematoxylin and eosin stain (2503) reveals lymphocytic interstitial inflammation (open arrows), interstitial fibrosis (arrowhead), and proximal tubular injury with nuclear enlargement, vacuolization, and desquamation (closed arrows). Glomeruli not shown. Key Teaching Point This case illustrates the potential for delayed-onset immunemediated kidney injury in patients with preexisting tubular damage because of chemotherapy. Although tazemetostat is not widely recognized as nephrotoxic, its introduction in a patient with prior ifosfamide-induced Fanconi syndrome may have served as a secondaryimmunologic trigger, unmasking or intensifying latent inflammation in already compromised tubules. (Text and image provided by Ahmad Matarneh, Department ofNephrology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania; Sundus Sardar, Department of Nephrology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania; Catherine Abendroth, Department of Pathology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania; Steven Salvatore, Department of Pathology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania; Monali Vasekar, Department of Hematology and Oncology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania; Evan Rosenbaum, Department of Nephrology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania; Victoria Gutgarts, Department of Medicine, Renal Service, Memorial Sloan Kettering Cancer Center, New York, New York; Nasrollah Ghahramani, Department of Nephrology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania; Naman Trivedi, Department of Nephrology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania) CJASN 21:3, 2026. DOI:10.2215/CJN.0000000821