Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive lymphoma subtype that predominantly affects young adults and is commonly treated with dose-adjusted EPOCH-R (DA-EPOCH-R), which provides high response and cure rates. Despite its efficacy, intensive chemotherapy regimens may lead to rare but clinically significant metabolic and renal complications. Here, we report a case of acute kidney injury (AKI) developing during DA-EPOCH-R therapy, most consistent with isolated acute uric acid nephropathy in the absence of classical tumor lysis syndrome (TLS).