Abstract: FR-PO934
Podocyte-Derived Vesicles as Urinary Markers of Kidney Function
Session Information
- Glomerular Diseases: Potpourri
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Schnobrich, Luisa, Universitat Regensburg Fakultat fur Biologie und Vorklinische Medizin, Regensburg, Bayern, Germany
- Stark, Klaus J., Universitat Regensburg Fakultat fur Medizin, Regensburg, Bayern, Germany
- Castrop, Hayo, Universitat Regensburg Fakultat fur Biologie und Vorklinische Medizin, Regensburg, Bayern, Germany
Background
Changes in the integrity of the glomerular filtration barrier (GFB) cause the endocytosis of albumin by podocytes from the subpodocyte space, as shown by intravital imaging in rats. Albumin-containing podocyte-derived vesicles are subsequently released into the urinary space and can be recovered from the urine. These vesicles are characterized by the presence of podocalyxin.
Based on these results we hypothesized that urinary vesicular albumin (vACR) and vesicular podocalyxin (vPCR) may serve as early biomarkers of changes of the integrity of the GFB in humans.
Methods
Urinary vesicles were isolated by ultracentrifugation from spot urine samples collected from participants of a prospective study, a cohort of mobile elderly subjects (aged 70 years +). Urine samples were collected and an array of clinical parameters was determined at baseline (BL: n = 626), after 3 years (follow-up 1: n = 626) and after 7 years (follow-up 2: n = 197). Vesicular albumin and podocalyxin concentrations were measured using commercially available ELISA kits and results were normalized to urinary creatinine concentration. Using SPSS 28.0.0.0 the association between vesicular parameters and clinical parameters (eGFRCys, urinary albumin/creatinine ratio (uACR), and alpha-1-microglobulin/creatinine ratio (a1M/Cr)) were determined.
Results
A negative association between eGFRCys and vACR was observed for all time points (p<.001). Annual changes in eGFRCys were not predicted by vesicular variables. Linear regression analysis between vACR or vPCR and uACR or a1M/Cr, both adjusted for age, sex and eGFRCys, showed a positive association between the variables at all timepoints (p<.05). Thus, elevated vACR and vPCR were accompanied by increased uACR and a1M/Cr concentrations. Increased vACR and vPCR concentrations at baseline were associated with a reduced increase of uACR over time, suggesting that the formation of podocyte-derived vesicles reduces the progression of albuminuria by some protective effect on the filtration barrier (p<.01).
Conclusion
In summary, increased vACR is associated with decreased GFR, and both vACR and vPCR are associated with the degree of albuminuria and tubular dysfunction. Our data suggests that both vACR and vPCR may serve as new biomarkers of kidney function and may predict the development of albuminuria over time.
Funding
- Government Support – Non-U.S.