Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Internal Medicine, Mount Sinai Morningside/West, New York, New York.
Clin J Am Soc Nephrol. 2023 Sep 1;18(9):1175-1185. doi: 10.2215/CJN.0000000000000219. Epub 2023 Jun 29.
Dasatinib has been associated with nephrotoxicity. We sought to examine the incidence of proteinuria on dasatinib and determine potential risk factors that may increase dasatinib-associated glomerular injury.
We examined glomerular injury through urine albumin-creatinine ratio (UACR) in 82 patients with chronic myelogenous leukemia who were on tyrosine-kinase inhibitor therapy for at least 90 days. t tests were used to compare mean differences in UACR, while regression analysis was used to assess the effects of drug parameters on proteinuria development while on dasatinib. We assayed plasma dasatinib pharmacokinetics using tandem mass spectroscopy and further described a case study of a patient who experienced nephrotic-range proteinuria while on dasatinib.
Participants treated with dasatinib ( n =32) had significantly higher UACR levels (median 28.0 mg/g; interquartile range, 11.5-119.5) than participants treated with other tyrosine-kinase inhibitors ( n =50; median 15.0 mg/g; interquartile range, 8.0-35.0; P < 0.001). In total, 10% of dasatinib users exhibited severely increased albuminuria (UACR >300 mg/g) versus zero in other tyrosine-kinase inhibitors. Average steady-state concentrations of dasatinib were positively correlated with UACR ( ρ =0.54, P = 0.03) and duration of treatment ( P = 0.003). There were no associations with elevated BP or other confounding factors. In the case study, kidney biopsy revealed global glomerular damage with diffuse foot process effacement that recovered on termination of dasatinib treatment.
Exposure to dasatinib was associated with a significant chance of developing proteinuria compared with other similar tyrosine-kinase inhibitors. Dasatinib plasma concentration significantly correlated with higher risk of developing proteinuria while receiving dasatinib.
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_09_08_CJN0000000000000219.mp3.
达沙替尼可引起肾毒性。我们试图研究达沙替尼治疗患者蛋白尿的发生率，并确定可能增加达沙替尼相关性肾小球损伤的潜在危险因素。
我们通过尿白蛋白/肌酐比值（UACR）检测 82 例接受酪氨酸激酶抑制剂治疗至少 90 天的慢性髓性白血病患者的肾小球损伤。采用 t 检验比较 UACR 的平均值差异，采用回归分析评估达沙替尼治疗期间药物参数对蛋白尿发展的影响。我们采用串联质谱法检测达沙替尼的血药浓度，并进一步描述了一名达沙替尼治疗期间发生肾病范围蛋白尿的患者的病例研究。
接受达沙替尼治疗的患者（ n =32）UACR 水平明显高于接受其他酪氨酸激酶抑制剂治疗的患者（ n =50；中位数 28.0mg/g；四分位距，11.5-119.5）（ P < 0.001）。接受达沙替尼治疗的患者中有 10%（ n =3）出现严重白蛋白尿（UACR >300mg/g），而接受其他酪氨酸激酶抑制剂治疗的患者中无一例出现（ P < 0.001）。达沙替尼的平均稳态浓度与 UACR（ ρ =0.54， P =0.03）和治疗持续时间呈正相关（ P =0.003）。与高血压或其他混杂因素无关。在病例研究中，肾活检显示弥漫性足突融合的全肾小球损伤，在停止达沙替尼治疗后恢复。
与其他类似的酪氨酸激酶抑制剂相比，达沙替尼暴露与蛋白尿发生的显著风险相关。达沙替尼血浆浓度与达沙替尼治疗期间蛋白尿发生风险显著相关。
