Recent Progression and Treatment Approaches of Kidney Fibrosis: Evidence to Clinic Approach

Mansi Sharma; Mansi Khanna; Pranjal Kumar; Ghanshyam Das Gupta; Kalicharan Sharma

doi:10.2174/0118715303374764250612052832

Recent Progression and Treatment Approaches of Kidney Fibrosis: Evidence to Clinic Approach

Endocr Metab Immune Disord Drug Targets. 2025 Jun 19. doi: 10.2174/0118715303374764250612052832. Online ahead of print.

Authors

Mansi Sharma¹, Mansi Khanna¹, Pranjal Kumar¹, Ghanshyam Das Gupta², Kalicharan Sharma³

Affiliations

¹ Department of Pharmacology, SPS, DPSRU, New Delhi,110017, India.
² Department of Pharmaceutics, ISF College of Pharmacy, Moga 142001, Punjab, India.
³ Department of Pharmaceutical Chemistry and Analysis, ISF College of Pharmacy, Moga-142001, Punjab, India.

PMID: 40551698
DOI: 10.2174/0118715303374764250612052832

Abstract

Background: Fibrosis is a pathological complication that arises from an abnormal tissue healing response to chronic inflammation or repeated injury. It is characterized by Excessive Extracellular Matrix (ECM) deposition, leading to progressive organ dysfunction. Chronic Kidney Disease of unknown etiology (CKDu) is a newly recognized public health crisis characterized by slow, irreversible progression and late-stage asymptomatic onset.

Objectives: To identify and analyze therapeutic targets, experimental strategies, and emerging treatments for renal fibrosis, with a focus on CKDu.

Methods: Experimental data on potential therapeutic targets, including CCR1 inhibitors, CCL2- CCR2 inhibitors, CTGF inhibitors, ET-1 antagonists, Nox1/4 inhibitors, TGF-β antagonists, and TNF-α antagonists, were compiled and analyzed. Specific attention was given to the roles of Cx43 (Connexin 43) and DDR1 (Discoidin Domain Receptor 1) in fibrosis. Data on phytopharmaceuticals, such as LIVON-S (Silymarin) and bio-fibrin, as well as emerging treatments like stem cell therapies, were gathered and reviewed.

Results: Therapeutic targets address key molecular pathways involved in fibrogenesis, including chemokine signaling (CCR1, CCR2, and CCL2), pro-fibrotic mediators (TGF-β and CTGF), and oxidative stress (Nox1/4). Phytopharmaceuticals, such as silymarin and bio-fibrin, demonstrated antifibrotic potential through their anti-inflammatory and ECM-modulating effects. Preclinical studies on stem cell therapies highlighted regenerative benefits in managing renal fibrosis. Experimental data on Cx43 and DDR1 supported their role in fibrotic progression and potential as therapeutic targets.

Conclusion: The study provides a comprehensive analysis of antifibrotic strategies, including validated molecular targets, phytopharmaceuticals, and innovative therapies like stem cell treatments. These findings underscore the need for focused research and development of effective interventions for CKDu and related fibrotic diseases.

Keywords: Fibrosis; albuminuria; diabetic nephropathy; kidney; silymarin..