Dasatinib-Induced Nephrotic Syndrome: A Case Report

Abstract

Second-generation tyrosine kinase inhibitors (TKI), such as nilotinib and dasatinib, are used in the first-line treatment of chronic myeloid leukemia (CML), usually after the failure or resistance to imatinib. Despite a good safety profile, medications in this category have an increased incidence of specific adverse events such as pulmonary hypertension, pleural effusion, and cardiovascular/peripheral arterial events. However, renal complications are rarely reported and observed. We herein report a case of a 46-year-old patient with CML who developed nephrotic syndrome upon switching from imatinib to dasatinib therapy, with the resolution of symptoms upon treatment discontinuation and switching to nilotinib. Limited cases were reported in the literature. It is thought that the inhibition of the vascular endothelial growth factor (VEGF) pathway is the main mechanism leading to proteinuria. Dasatinib-induced nephrotic syndrome should be looked for as it can be resolved by either reducing the dose or stopping it altogether and switching to another TKI.

A Case of Imatinib Induced Nephrotic Syndrome in a Child with Chronic Myeloid Leukaemia

“…Abnormalities in VEGF expression have been implicated in the pathogenesis of minimal change disease and other glomerulopathies 11 .Another potential mechanism of renal injury by TK inhibitors is reduction of nitric oxide production by endothelial cells, leading to hypertension, which in turn may increase proteinuria 12 .There are several other reports of nephrotic syndrome in adults caused by Dasatinib are available. In all cases, discontinuation or reduction of the dose of Dasatinib or a switch to a first-generation TKI improved proteinuria 13,14 . Hirano et al proposed that the severity of proteinuria was dose-dependent, because reducing the dose by half was efficient in their study 15 .…”

Adverse reactions after treatment with dasatinib in chronic myeloid leukemia: Characteristics, potential mechanisms, and clinical management strategies

“…A previous study showed that the incidence of proteinuria in patients treated with dasatinib was 18%, and grade 3/ 4 events were rare (64). To our knowledge, thus far, nine cases of nephrotic syndrome caused by dasatinib have been reported (three children, six adults) (65)(66)(67)(68)(69)(70)(71)(72).…”

Dasatinib induced nephrotic range proteinuria in pediatric patient with acute lymphoblastic leukemia with hyper-eosinophilia

“…5,6 Mechanistically, dasatinib’s inhibition of the vascular endothelial growth factor (VEGF) pathway is considered to be the main mechanism promoting the development of proteinuria. 4 Here we report a case of a 14-year-old male with high-risk B-ALL and hypereosinophilia related to his translocation t(5:14)/ IGH:IL3 who was treated with dasatinib and subsequently developed nephrotic syndrome likely related to the use of dasatinib.…”

“…1 Case reports in patients with CML have demonstrated proteinuria and nephrotic syndrome. [2][3][4] Nephrotic syndrome is defined as proteinuria which can be urine protein/creatinine ratio ⩾200 mg/mmol or 3+ protein (⩾300 mg/dL) on urine dipstick, hypoalbuminemia, presence of edema and hyperlipidemia. 5,6 Mechanistically, dasatinib's inhibition of the vascular endothelial growth factor (VEGF) pathway is considered to be the main mechanism promoting the development of proteinuria.…”