Kidney Week

Abstract: SA-PO326

Impact of Vertical Sleeve Gastrectomy (VSG) on Early Diabetic Nephropathy

Session Information

• Diabetic Kidney Disease: Clinical Pathology, Diagnostic and Treatment Advances
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

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

Abhijit S. Naik, MD, MPH, FASN

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

Fadhl Alakwaa, PhD

• Schaub, Jennifer A., University of Michigan, Ann Arbor, Michigan, United States

Jennifer A. Schaub, MD

• McCown, Phillip J., University of Michigan, Ann Arbor, Michigan, United States

Phillip J. McCown, MS, PhD

• Nair, Viji, University of Michigan, Ann Arbor, Michigan, United States

Viji Nair, PhD

• Annese, Francesca, University of Michigan, Ann Arbor, Michigan, United States

Francesca Annese, MD

• Otto, Edgar A., University of Michigan, Ann Arbor, Michigan, United States

Edgar A. Otto, PhD

• Choi, Ye Ji, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Ye Ji Choi, MPH

• Ryder, Justin R., Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, United States

Justin R. Ryder, PhD

• Pyle, Laura, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Laura Pyle, PhD

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

Kristen Nadeau, MD

• Brosius, Frank C., Banner - University Medical Center Tucson, Tucson, Arizona, United States

Frank C. Brosius, MD

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

Matthias Kretzler, MD

• Bjornstad, Petter, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Petter Bjornstad, MD

Background

We explored the impact of VSG on the progression of early diabetic nephropathy (DN) in an adolescent cohort with obesity and type 2 diabetes (T2D).

Methods

5 of 12 patients from IMPROVE study had renal biopsies before and 1year after VSG. MRI measured change in total kidney volumes (TKV). Kidney tissue was profiled using histology, single-cell RNAseq (scRNAseq), and proteomics. Renal function was measured by assessing glomerular filtration rate (GFR) and albuminuria. Somascan data from TeenLABS study(n=62) was used to evaluate circulating proteomic changes pre- and post. The longitudinal TODAY study provided an association between change in circulating proteome with albuminuria.

Results

All participants had a reduction in weight, BMI, GFR, albuminuria, mean arterial pressure, and insulin resistance. The TKV decreased by 18%. Tissue morphometry showed reductions in glomerular volume, indicating resolving glomerular hypertrophy. scRNA-seq of the proximal tubule (PT) showed enrichment of evolutionarily conserved PRKAA2 (AMPK) and FOXO3-mediated transcription factors post-VSG, consistent with cells experiencing 'starvation stress.' There was a coordinated reduction in transcripts of gluconeogenesis, TCA cycle, ROS mitigation machinery and an increase in Insulin-IGF-1 Signaling (IIS), mitochondrial biogenesis, apoptosis and mitophagy. Circulating proteomic analysis from TeenLABS showed reduced IIS-mediated signaling aligned with the intrarenal transcriptional response after VSG. TODAY participants had decreased albuminuria at 15 years among pathways enriched in TeenLABS participants.

Conclusion

VSG induces a coordinated activation of AMPK and FOXO3-mediated transcription factors in youth-onset T2D, resetting molecular programs in the PT with reversal of early DN. These findings are currently undergoing proteomic validation.

Funding

• NIDDK Support