Kidney Week

Abstract: TH-PO1209

Vertical Sleeve Gastrectomy Reprograms Endothelial, Tubular, and Immune Compartments in Youth-Onset Diabetic Kidney Disease

Session Information

• Late-Breaking Research Posters
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Yuan, Long, Johns Hopkins Medicine, Baltimore, Maryland, United States

Long Yuan, MMSc

• Choi, Ye Ji, University of Washington School of Medicine, Seattle, Washington, United States

Ye Ji Choi, MPH

• Naik, Abhijit S., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Abhijit S. Naik, MD, MPH, FASN

• Alakwaa, Fadhl, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Fadhl Alakwaa, PhD

• Nadeau, Kristen, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Kristen Nadeau, MD

• Tommerdahl, Kalie L., University of Washington School of Medicine, Seattle, Washington, United States

Kalie L. Tommerdahl, MD, MS

• Hampson, Hailey E, University of Washington School of Medicine, Seattle, Washington, United States

Hailey E Hampson, MS, PhD

• Goodrich, Jesse Allen, University of Southern California, Los Angeles, California, United States

Jesse Allen Goodrich, PhD

• Narongkiatikhun, Phoom, Chiang Mai University, Chiang Mai, Thailand

Phoom Narongkiatikhun, MD

• van Raalte, Daniël H., Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands

Daniël H. van Raalte, MD, PhD

• Pyle, Laura, University of Washington School of Medicine, Seattle, Washington, United States

Laura Pyle, MS, PhD

• Kretzler, Matthias, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Matthias Kretzler, MD

• Bjornstad, Petter, University of Washington School of Medicine, Seattle, Washington, United States

Petter Bjornstad, MD

Background

Youth-onset diabetic kidney disease (YO-DKD) progresses rapidly and lacks effective therapies. Bariatric surgery, particularly vertical sleeve gastrectomy (VSG), improves systemic metabolism, but its kidney mechanisms remain poorly defined.

Methods

We performed single-cell RNA-seq on kidney biopsies from individuals with obesity and YO-DKD pre- and post-VSG (N=9) or standard medical therapy (SMT; N=2). Analyses included lineage trajectories (Slingshot), longitudinal differential expression (linear mixed models), and high-dimensional weighted gene co-expression network analysis (hdWGCNA).

Results

Baseline age 17±2 years; 45% male; pre- and 12 month post-VSG BMI 43.8±7.0 and 33.7±8.1 kg/m². Trajectory analysis confirmed known proximal tubule (PT) disease progression and uncovered novel endothelial (EC) and thick ascending limb (TAL) trajectories (Fig.1A). VSG induced greater transcriptional remodeling than SMT, particularly in PT, TAL, and EC (Fig.1B). EC subsets showed interferon and antigen presentation enrichment with suppression of insulin resistance programs (Fig.1C). hdWGCNA revealed preserved PT solute and TAL transport modules under VSG, alongside suppression of PT injury/fibrosis and EC damage programs (Fig.1D).

Conclusion

VSG reprograms kidney architecture in YO-DKD by reducing inflammation, dampening vascular remodeling, and preserving tubular and endothelial function. These findings provide the first lineage- and program-level atlas of bariatric surgery’s kidney benefits, establishing endothelial–immune crosstalk and tubular transport preservation as mechanistic axes of surgical protection.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025yg103s54