LDP alleviates TKI-induced proteinuria through reversing the expression of RelA in renal tissues

Area of Science:

• Nephrology
• Oncology
• Pharmacology

Background:

• Tyrosine kinase inhibitors (TKIs) are crucial cancer therapies but can cause severe proteinuria, complicating treatment.
• Current proteinuria treatments are ineffective against TKI-induced kidney damage.
• Podocyte injury, linked to the RelA signaling pathway, is a key factor in various proteinurias.

Purpose of the Study:

• To investigate the efficacy of Liuwei Dihuang Pill (LDP) in mitigating TKI-induced proteinuria.
• To explore the underlying mechanisms of LDP's action on the RelA signaling pathway and podocyte injury.

Main Methods:

• Experiments confirmed TKI-induced activation of the renal RelA signaling pathway, leading to podocyte death and glomerular filtration barrier damage.
• The study evaluated LDP's effect on podocyte inflammation and RelA activation.
• Assessment of LDP's impact on TKI-related proteinuria, thrombotic microangiopathy (TMA), and focal segmental glomerulosclerosis (FSGS) progression.

Main Results:

• TKIs activate the renal RelA pathway, causing podocyte damage and proteinuria.
• LDP was found to inhibit RelA activation, thereby attenuating inflammatory podocyte injury.
• LDP treatment effectively relieved TKI-induced proteinuria and prevented the progression of TMA and FSGS.

Conclusions:

• LDP demonstrates potential as an effective treatment for TKI-induced proteinuria.
• Inhibition of the RelA pathway by LDP offers a novel therapeutic strategy for managing TKI-related kidney complications.
• These findings hold significant clinical implications for cancer patients undergoing TKI therapy.