Acute kidney injury from bilateral renal infiltration is rare in diffuse large B-cell lymphoma (DLBCL). We present the case of a 45-year-old woman with a three-month history of night sweats, weight loss, fever, and fatigue. Clinical evaluation revealed anemia, edema, cervical lymphadenopathy, and elevated blood pressure. Initial lab results indicated severe kidney injury, initially suspected to be chronic kidney disease, later ruled out. Radiological assessments confirmed mediastinal lymphadenopathy. A cervical lymph node biopsy led to a diagnosis of DLBCL. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy improved renal function and hematological parameters. Subsequent staging CT confirmed lymphadenopathy. Close monitoring revealed a complete return to normal renal function after one month. Further follow-up was missed. This case emphasizes diagnostic complexities and the value of a multidisciplinary approach in managing complex clinical presentations.