Kidney Week

Abstract: FR-PO0221

Alternative Complement Pathway Inhibition with Antifactor B Antibody Restores Endothelial Function in CKD

Session Information

• CKD: Mechanisms of Injury and Fibrosis - 2
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2203 CKD (Non-Dialysis): Mechanisms

Authors

• Sun, Mingyao, The University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa, United States

Mingyao Sun, PhD

• Nagel, Ryan T., The University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa, United States

Ryan T. Nagel

• Manning, Trejahn E., The University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa, United States

Trejahn E. Manning

• Thurman, Joshua M., University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States

Joshua M. Thurman, MD, FASN

• Smith, Richard J., The University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa, United States

Richard J. Smith, MD

• Jalal, Diana I., The University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa, United States

Diana I. Jalal, MD, FASN

Background

Alternative pathway (AP) dysregulation contributes to kidney and cardiovascular disease (CVD). Specifically genetic variants of Cfh that result in FH deficiency may increase the risk of CVD and kidney disease progression. We previously demonstrated that reduced kidney function activates the AP of complement and promotes endothelial dysfunction in a murine chronic kidney disease (CKD) model. We hypothesized that inhibition of the AP improves endothelial dysfunction in CKD.

Methods

Cfh+/− mice were subjected to 5/6 nephrectomy (5/6Nx) to induce CKD. 10-12 weeks following CKD induction, mice were randomized to receive either control IgG or anti-factor B monoclonal antibody (mAb 1379; 1 mg/day, intraperitoneally) for three consecutive days. Glomerular filtration rate (GFR) was assessed by transcutaneous FITC-sinistrin clearance (MediBeacon, St. Louis, MO). Plasma levels of FH, C3, and C3a were quantified by ELISA. Endothelium-dependent dilation (EDD) and independent dilation (EID) were determined via myography by dose-response curves to acetylcholine (ACh, 10⁻⁹–10⁻⁵ M) and sodium nitroprusside (SNP, 10⁻⁹–10⁻⁵ M), respectively, following phenylephrine (PE, 10⁻⁶ M)-induced preconstriction. Statistical analyses were performed using GraphPad Prism version 10 (GraphPad Software, San Diego, CA). Comparisons between treatment groups were analyzed using unpaired Student's t-tests.

Results

Pharmacologic inhibition of the AP with anti-factor B mAb 1379 significantly improved EDD in Cfh+/− CKD mice compared with IgG-treated controls (Table 1). Improvement in EDD was accompanied by normalization of complement activation, as demonstrated by increased circulating C3 and C3a levels following anti-factor B treatment. In contrast, EID was unchanged between treatment groups.

Conclusion

These findings demonstrate that factor B inhibition attenuates AP activity and restores endothelial function in Cfh+/− CKD mice and suggest that factor B inhibition may represent a targeted therapeutic approach to modify kidney and cardiovascular risk in individuals with FH deficiency and progressive CKD.

Acknowledgment

The work is funded by the American Heart Association (grant 23TPA1077563 [Jalal]) and the National Institutes of Health (R01DK133240 [MPI Jalal, Smith, Thurman] and R01DK076690 [Thurman]).

Funding

• NIDDK Support