Kidney Week

Abstract: FR-PO0667

Resolvin D1 Attenuates Renal Inflammation and Cyst Growth in Mice with PKD

Session Information

• Cystic Kidney Diseases: Basic and Translational Research
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases

Authors

• Zhang, Yan, Michigan Technological University, Houghton, Michigan, United States

Yan Zhang, PhD

• Zhang, Yang, Michigan Technological University, Houghton, Michigan, United States

Yang Zhang, APN, APRN

• Wei, Aiping, Michigan Technological University, Houghton, Michigan, United States

Aiping Wei, APN

• Xu, Yu, Michigan Technological University, Houghton, Michigan, United States

Yu Xu, MBBS

• Gregersen, Tyler Kaedyn, Michigan Technological University, Houghton, Michigan, United States

Tyler Kaedyn Gregersen

• Schneider, Jaden, Michigan Technological University, Houghton, Michigan, United States

Jaden Schneider

• Detterman, Nicholas Don, Michigan Technological University, Houghton, Michigan, United States

Nicholas Don Detterman

• Stubbs, Jason R., The University of Kansas Medical Center, Kansas City, Kansas, United States

Jason R. Stubbs, MD

• Wallace, Darren P., The University of Kansas Medical Center, Kansas City, Kansas, United States

Darren P. Wallace, PhD

Background

In autosomal-dominant polycystic kidney disease (PKD), chronic inflammation induces tubular injury and promotes cyst growth and fibrosis, key features driving renal function decline. Specialized pro-resolving mediators (SPMs) are endogenous lipid derivatives that promote inflammation resolution and restore tissue homeostasis. Resolvin D1 (RvD1) is an SPM derived from docosahexaenoic acid (DHA) that regulates renal innate immunity. Acute kidney injury (AKI) triggers renal RvD1 biosynthesis, and exogenous RvD1 treatment prevents kidney damage in AKI models. RvD1 interacts with FPR2, a G protein-coupled receptor, to suppress NF-κB. The potential therapeutic effects of RvD1 in PKD have not been investigated.

Methods

We performed lipidomic analyses to determine levels of SPMs derived from DHA and pro-inflammatory lipid mediators in the kidneys of age- and sex-matched Pkd1^RC/RC mice and Pkd1^RC/+ controls. To evaluate RvD1's effects on PKD progression, we conducted short- and long-term studies with RvD1 (20 and 100 μg/kg) or vehicle, administered on alternating days by IP injection in Pkd1^RC/RC mice. Lastly, we defined the effects of RvD1 through FPR2/NF-κB signaling.

Results

Lipidomic analyses revealed a reduction in RvD1 and its precursor 17-hydroxy-DHA, along with an increase in pro-inflammatory lipid mediators, including prostaglandin E2 and thromboxane B2, in Pkd1^RC/RC mice compared to controls. RvD1 administration for one week resulted in a dose-dependent reduction in renal NF-κB activation, mRNA levels of TNF-α, IL-1β, and MCP-1, and macrophage accumulation in Pkd1^RC/RC kidneys. RvD1 also increased IL-10 expression, an anti-inflammatory mediator. Furthermore, chronic administration of RvD1 (20 μg/kg over 10 weeks) inhibited renal inflammation, reduced cyst burden, and attenuated renal fibrosis. Finally, mechanistic studies revealed prominent immunostaining of FPR2 in cystic epithelial cells, and in vitro RvD1 treatment of primary renal epithelial cells from Pkd1^RC/RC mice reduced NF-κB and TNF-α expression.

Conclusion

Our data suggest that impaired RvD1 biosynthesis contributes to kidney inflammation in PKD, and exogenous RvD1 treatment promotes inflammation resolution through FPR2/NF-κB signaling. These findings imply that RvD1 administration may be a novel therapeutic approach for PKD treatment.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025em5ye3pp