Gayathri J S, Krishna S Swathi, Rakesh M P
Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Health Science Campus, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, India.
Department of Medical Oncology, Amrita Health Science Campus, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, India.
Drug Res (Stuttg). 2025 Jan;75(1):5-11. doi: 10.1055/a-2423-3533. Epub 2024 Oct 15.
Tyrosine Kinase inhibitor (TKI) is a class of drugs that interfere with protein kinases' signal transduction pathways through an array of inhibitory mechanisms. Tyrosine kinases (TK) have an inevitable role in downstream signal transduction and the proliferation of tumour cells. Hence, tyrosine kinase inhibitors (TKIs) are frequently employed as anti-neoplastic agents in the treatment of colon, breast, kidney, and lung cancers. They can be used as single or combination therapy with other targeted therapies. It is understood that TKIs pose a risk of developing proteinuria in some patients as it can primarily result in dysfunction of the split diaphragm, constriction or blockage of capillary lumens mediated by the basement membrane, acute interstitial nephritis, or acute tubular necrosis. This paper reviews the mechanism of action of TKIs, the pathophysiological mechanism of TKI-induced proteinuria, and its management Fig. 1.
酪氨酸激酶抑制剂(TKI)是一类通过一系列抑制机制干扰蛋白激酶信号转导途径的药物。酪氨酸激酶(TK)在肿瘤细胞的下游信号转导和增殖中起着不可或缺的作用。因此,酪氨酸激酶抑制剂(TKIs)经常被用作抗肿瘤药物来治疗结肠癌、乳腺癌、肾癌和肺癌。它们可以作为单一疗法或与其他靶向疗法联合使用。据了解,TKIs在一些患者中存在发生蛋白尿的风险,因为它主要可导致裂孔隔膜功能障碍、由基底膜介导的毛细血管腔狭窄或阻塞、急性间质性肾炎或急性肾小管坏死。本文综述了TKIs的作用机制、TKI诱导蛋白尿的病理生理机制及其处理(图1)。