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Updated: Jun 10, 2025

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Tyrosine Kinase Inhibitor Induced Proteinuria - A Review
J S Gayathri1, S Swathi Krishna1, M P Rakesh2
1Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Health Science Campus, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, India.
Abstract:
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.
Insights
Tyrosine Kinase Inhibitors (TKIs) treat cancers but can cause proteinuria by damaging kidney structures. This review details TKI action, kidney damage mechanisms, and management strategies.
Area of Science:
- Oncology
- Nephrology
- Pharmacology
Background:
- Tyrosine Kinase Inhibitors (TKIs) are crucial targeted therapies for various cancers, including lung, breast, kidney, and colon cancer.
- TKIs function by inhibiting tyrosine kinases (TK), which are vital for tumor cell proliferation and signal transduction.
- While effective, TKIs are associated with adverse effects, notably proteinuria, impacting patient treatment and outcomes.
Purpose of the Study:
- To elucidate the mechanism of action of Tyrosine Kinase Inhibitors (TKIs).
- To review the pathophysiological mechanisms underlying TKI-induced proteinuria.
- To discuss current management strategies for TKI-induced proteinuria.
Main Methods:
- Literature review of TKI mechanisms.
- Analysis of pathophysiological pathways leading to TKI-induced kidney damage.
- Synthesis of clinical data on proteinuria management in patients on TKIs.
Main Results:
- TKIs interfere with critical signaling pathways, leading to anti-neoplastic effects.
- TKI-induced proteinuria can stem from podocyte injury, glomerular basement membrane alterations, acute interstitial nephritis, or acute tubular necrosis.
- Proteinuria management involves dose adjustment, supportive care, and potentially discontinuation of TKI therapy.
Conclusions:
- Understanding TKI action is key to managing their side effects.
- TKI-induced proteinuria is a significant concern requiring careful monitoring and intervention.
- Effective management strategies are essential for optimizing cancer treatment with TKIs while mitigating renal risks.
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