Kidney Week

Abstract: FR-PO1009

Renal Microvascular Inflammation in Human Obesity Detected by Urinary Extracellular Vesicles

Session Information

• CKD Mechanisms: From Mendel to Mars
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Al Saeedi, Mina H., Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Mina H. Al Saeedi,

• Jordan, Kyra L., Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Kyra L. Jordan,

• Zhu, Xiang yang, Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Xiang yang Zhu,

• Eirin, Alfonso, Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Alfonso Eirin,

• Lerman, Lilach O., Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Lilach O. Lerman,

Background

Obesity is characterized by systemic inflammation and activation of the inflammatory marker monocyte chemoattractant protein (MCP)-1, but the involvement of inflammation in early renal injury is unclear. Plasmalemmal vesicle-associated protein (PLVAP), a marker of renal peritubular capillaries, is upregulated in diabetes. We hypothesized that human obesity induces renal microvascular inflammation detectable by elevated levels of PLVAP+/MCP-1+ urinary extracellular vesicles (uEVs).

Methods

Obese patients (OB, n=6) and healthy volunteers (HV, n=7) were prospectively enrolled. Blood and urine were collected, and uEVs were isolated (Total Exosome). uEVs were quantified (Nanoparticle Tracking Analysis) and characterized (Flow cytometry) for CD31, PLVAP, CD144 (expressed on glomerular endothelium), and MCP-1, and their relationship with body mass index (BMI) and serum glucose levels was evaluated.

Results

OB had significantly higher BMI than HV, but both groups showed preserved renal function and glucose levels (Table-1), and a similar number and size of uEV. However, the fraction of CD31-/PLVAP+/CD144-/MCP-1+ was higher in OB and directly correlated with both glucose levels and BMI in OB but not in HV (Figure-1).

Conclusion

Non-diabetic obese patients show elevated numbers of PLVAP+/MCP-1+ uEVs that correlate with BMI and glucose levels. These early markers of renal microvascular inflammation that herald the development of pre-diabetes might be useful in the management of patients with obesity.

Demographics (mean± standard deviation (SD) or median(min,max))

*P<0.05 vs. HV

Figure-1

Funding

• NIDDK Support