Renal-Limited Thrombotic Microangiopathy in a Patient Who Received Gemcitabine, Ramucirumab, and Pembrolizumab: A Case Report and Literature Review

Abstract

Cancer drug-induced thrombotic microangiopathy (DITMA) is an important and serious cause of kidney disease in cancer patients. In addition to classical chemotherapy, the increasing use of targeted therapy and immunotherapy has led to more oncotherapy-associated thrombotic microangiopathy (TMA). It is important for clinicians to recognize this potentially life-threatening adverse effect and gain knowledge of the patient's clinical course and treatment response. In this paper, we report a patient with lung cancer, who was treated with three different classes of anti-neoplastic agents, gemcitabine, ramucirumab, and pembrolizumab. This patient subsequently developed renal-limited thrombotic microangiopathy(rTMA) requiring hemodialysis. The varying features of TMA caused by these therapies were discussed. We also described the clinical course, diagnostic challenges, and management of this patient.

Keywords: acute kidney injury (aki); anti-neoplastic therapy; cancer drug induced tma; cancer treatment side effects; thrombotic microangiopathy (tma).

Figure 1. Association of timing of drug dose with hemoglobin, platelet, and creatinine.

*Urothelial cancer was diagnosed. #Non-small cell lung cancer was diagnosed. ^Lactate dehydrogenase on T+36 was 366 and on T+40 was 316 (normal value: 135-214 units/L); haptoglobin on T+36 was 257 and on T+40 was 135 (normal value: 30-200 mg/dL).

Figure 2. Light microscopic appearance of a glomerulus reveals global capillary wall wrinkling and double contour formation (arrows), consistent with remodeling due to thrombotic microangiopathy (periodic acid-Schiff stain; original magnification 400x).

Figure 3. Fibrinogen stain reveals segmental staining in the capillary loops, consistent with thrombotic microangiopathy (immunofluorescence stain; original magnification 400x).