Clinicopathological spectrum of kidney diseases in cancer patients treated with vascular endothelial growth factor inhibitors: a report of 5 cases and review of literature

Abstract

Recently, cancer therapies have been supplemented by vascular endothelial growth factor (VEGF) inhibitors as anti-angiogenic agents. However, kidney-related adverse reactions associated with these agents clinically manifest as hypertension and proteinuria, the most severe form being thrombotic microangiopathy (TMA). We present the spectrum of pathological features in VEGF inhibitor-associated kidney disease. Clinicopathological findings of kidney disease were retrospectively studied in 5 cancer patients treated with anti-VEGF agents. Although 4 cases received bevacizumab (anti-VEGF-A), one was given sorafenib (small molecule tyrosine kinase inhibitor affecting VEGF-R2). All patients presented with acute kidney injury, hypertension, and/or proteinuria. All kidney biopsies showed recent and chronic endothelial injury of varying severity and vascular sclerosis, including 2 with typical active features of TMA. Furthermore, acute tubular injury with focal necrosis was seen in all cases. While administration of VEGF inhibitor was discontinued in 4 cases, it was resumed for 5 more doses, following steroid therapy in 1 case. Cessation of VEGF inhibitor therapy was successful in reversing anemia and led to improvement of hypertension and proteinuria in 4 of the 5 cases. One case with TMA progressed to end-stage renal disease. A range of renal pathologic lesions secondary to endothelial injury are noted often accompanied by acute tubular damage following anti-VEGF therapy, the most severe being TMA. While most of the clinical manifestations are reversible with discontinuation of therapy, the role of other nephrotoxic chemotherapeutic agents in enhancing renal injury including severe TMA and other host factors with possible poor outcome should be considered.

Keywords: Acute tubular injury; Proteinuria; Renal failure; Thrombotic microangiopathy; Vascular endothelial growth factor inhibitor.