Precision Medicine in Kidney Disease: Targeting Scarring and Fibrosis

Emerging research from UCLA highlights a potential precision medicine approach to slow the progression of chronic kidney disease.

New findings from a UCLA-led study, published in Science Translational Medicine, have revealed how type 5 collagen contributes to kidney scarring and how this process could be disrupted to prevent chronic kidney disease (CKD) progression. Researchers identified the gene Col5a1, which encodes type 5 collagen, as a key regulator of fibrosis following kidney injury. Altered expression of this gene was associated with increased scar formation and greater risk of kidney failure.

In addition, the team identified the repurposed drug Cilengitide as a potential therapy to inhibit the fibrotic signaling pathway that becomes overactive in the absence of type 5 collagen. Together, these discoveries offer new directions for biomarker-guided, individualized treatment approaches in nephrology.

The Role of Type 5 Collagen in Kidney Injury

According to senior study author Dr. Arjun Deb of UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, type 5 collagen plays a foundational role in organizing scar tissue during healing. The research team examined both mouse models and data from the UK Biobank, a long-term study tracking over 1.5 million people, and found a strong correlation between Col5a1 expression and the likelihood of developing CKD.

In mouse models, animals with low Col5a1 levels experienced more severe fibrosis and progressed more rapidly to kidney failure after injury. The study found that reduced levels of type 5 collagen result in weaker, disorganized scar tissue, which activates αvβ3 integrin receptors in fibroblasts. This integrin signaling, in turn, promotes excessive collagen deposition and worsens kidney scarring.

Targeting Integrin Signaling With Cilengitide

Building on these insights, the researchers explored whether blocking integrin signaling could interrupt this cycle of fibrosis. They focused on Cilengitide, a drug previously developed for cancer treatment. Though it was ultimately ineffective in oncology, Cilengitide had passed safety evaluations in human trials, making it an appealing candidate for repurposing.

In their preclinical study, Cilengitide significantly reduced kidney fibrosis in mice with decreased Col5a1 expression, while having no effect in animals with normal expression levels. This specificity suggests that patients identified through Col5a1 testing may be particularly suited for targeted therapy with integrin inhibitors.

Col5a1 as a Biomarker for Risk Stratification

The UCLA research team is now developing a blood test to measure Col5a1 expression in CKD patients. If validated, this diagnostic tool could identify individuals at higher risk of fibrosis and kidney failure, enabling earlier and more precise interventions.

“Chronic kidney disease presents a large time window of opportunity for intervention,” said Dr. Deb. “We can use a simple blood test to measure type 5 collagen levels and identify individuals who could potentially benefit from this drug.”

This diagnostic-therapeutic pairing exemplifies precision medicine in practice: aligning molecular diagnostics with specific treatments to improve outcomes for patients with CKD.

Future Directions in CKD Management

This study highlights the importance of type 5 collagen in regulating tissue repair and the potential to repurpose existing therapies such as Cilengitide to target fibrosis in a more individualized way. If ongoing work confirms these findings in human populations, this approach could significantly impact the clinical management of chronic kidney disease by integrating biomarker testing into treatment planning.

Note: Cilengitide has not been approved by the FDA for use in treating fibrosis and has only been studied in preclinical models in this context.

Source

Deb, A., et al. (2025). Collagen V Regulates Renal Function After Kidney Injury and Can Be Pharmacologically Targeted to Enhance Kidney Repair in Mice. Science Translational Medicine. https://www.science.org/doi/10.1126/scitranslmed.ads7714