Dasatinib-induced nephrotic syndrome in a patient with chronic myelogenous leukemia: a case report

Abstract

Background Dasatinib is a second-generation tyrosine kinase inhibitor that is indicated for the treatment of patients with chronic myeloid leukemia. Here, we report the case of a man with nephrotic syndrome that was caused by dasatinib. Case presentation A 40-year-old man with chronic myeloid leukemia was referred to our hospital because of proteinuria 1 month after dasatinib therapy was introduced. A percutaneous kidney biopsy was performed, diffuse glomerular endothelial injury and effacement of the foot process were noted, and the patient was diagnosed with dasatinib-induced nephrotic syndrome. Additionally, in an electron microscopy study, randomly arranged fibrils were observed in the mesangial and subendothelial regions. Switching from dasatinib to nilotinib led to a decrease in the proteinuria level, from 12 to 0.6 g/g creatinine, within 2 weeks. The patient was discharged from our department on the 25th day after hospitalization, without any drug aftereffects. Conclusions Drug-related nephrotic syndrome should be considered when nephrotic syndrome develops during treatment with dasatinib.

Nephrotoxicity Associated with Novel Anticancer Agents (Aflibercept, Dasatinib, Nivolumab): Case Series and Nephrological Considerations

“…Biopsy specimens obtained in some cases of dasatinib-associated nephrotic proteinuria [ 31 , 32 , 34 , 35 , 37 ] revealed podocytopathy (minimal change disease), characterized by the effacement of the podocyte foot processes at electron microscopy analysis, as in our patient ( Figure 2 ). Podocytes are crucial for the establishment of the blood-urine filtration barrier in glomeruli, and the injury of them causes proteinuria.…”

“…To our knowledge, including the present one there are nine case reports of nephrotic syndrome caused by dasatinib reported in the scientific literature. Three cases affected children [ 31 , 32 , 33 ], and the remainder adults [ 30 , 34 , 35 , 36 , 37 ]. Nephrotic proteinuria developed after a duration of dasatinib administration ranging from 2 weeks [ 30 ] to 2 years [ 37 ].…”

“…Dose reduction [ 30 ] or the discontinuation [ 31 , 32 , 33 , 37 ] of dasatinib was associated with an improvement in proteinuria. Switching to a first-generation TKI such as imatinib [ 35 , 36 ] or nilotinib [ 34 ], or to the new second-generation TKI bosutinib [ 37 ], also proved an effective strategy.…”

Thrombotic microangiopathy in dasatinib-treated patients with chronic myeloid leukemia

“…After dasatinib was discontinued and replaced with imatinib, her spot urine protein-creatinine ratio decreased from 2.8 to 0.13 g/g in 2 weeks. Ochiai et al 3 described a case of a 40-year-old man with CML that developed nephrotic syndrome due to dasatinib. Biopsy showed diffuse glomerular endothelial injury and effacement of the foot process.…”

“…Endothelial injury is assumed as the main cause of renal involvement of dasatinib. [2][3][4][5][6] We present two kidney biopsy-proven thrombotic microangiopathy (TMA) cases of patients with CML who developed nephrotic-range proteinuria after initiation of dasatinib therapy that resolved after changing treatment to alternate TKIs. We also summarize the current literature of both TMA and nephrotic-range proteinuria from dasatinib.…”