Kidney function is typically monitored using traditional clinical markers, which lack sensitivity for early detection and often fail to capture subclinical renal changes. Urinary extracellular vesicles (uEVs), released from renal and urinary tract cells, have emerged as promising biomarkers of kidney health. Aging is a major risk factor for chronic kidney disease (CKD) and is associated with structural and functional declines in renal function. Age-related alterations in renal cell biology may influence uEV biogenesis and release. This study determined: 1) if circulating uEV levels increase with age, independent of other cardiometabolic risk factors; and 2) whether circulating uEVs are associated with age-related changes in MRI measures of renal function. Thirty healthy adults were studied: 15 young (27±2 years) and 15 older (67±6 years). Spot urine (~15 mL) was collected and processed using a standardized extracellular vesicle isolation workflow. Samples underwent sequential centrifugation (1,900×g 10 min; 16,000×g 50 min), 0.2 µm filtration, and Tamm–Horsfall protein removal. Particle size and concentration were assessed by nanoparticle tracking analysis (NTA). uEVs were labeled with CFSE and EV markers (CD9, CD63) and quantified by nanoscale flow cytometry. Renal function was measured by 3T multiparametric MRI: DWI (fibrosis, ADC), BOLD-MRI (oxygenation, R2*), and ASL (perfusion). Urine creatinine was measured by immunoassay. Older adults showed higher large-particle concentrations (200–900 nm) by NTA (6.57×10 8 ± 4.29×10 8 vs. 2.26×10 8 ± 1.46×10 8 particles/mL; p=0.003), with enrichment at 700–900 nm unique to the older group (2.63×10 6 ± 3.84×10 6 particles/mL). Flow cytometry confirmed higher uEV abundance with age: CFSE + /CD9 + (176±100 vs. 98±58 uEV/µL; p=0.01), CFSE + /CD63 + (1267±884 vs. 505±275 uEV/µL; p=0.004), CD9 + (432±278 vs. 241±106 uEV/µL; p=0.02), and CD63 + (1130±779 vs. 656±333 uEV/µL; p=0.04). Urine creatinine did not differ between groups (young: 60±26 vs. older: 73±26 mg/dL; p=0.18) and the differences in uEVs between groups persisted when corrected for urine creatinine. Older adults exhibited significantly lower ADC values in both the renal cortex (1662±77 vs. 1713±43 mm 2 /s; p=0.042) and medulla (1673±45 vs. 1717±55 mm 2 /s; p=0.033), indicative of increased renal fibrosis. Renal oxygenation was also reduced with age, with lower R2* values in the cortex (21.7±2.5 vs. 19.4±1.9 s - ¹; p=0.01) and medulla (26.6±2.7 vs. 22.5±2.7 s - ¹; p< 0.001). Additionally, cortical perfusion was 12% lower in older adults compared with young adults (265±40 vs. 298±17 mL/min/100 g; p=0.014). Circulating uEV were positively associated with renal fibrosis (r=0.47, p=0.01) and inversely associated with renal oxygenation (r=0.52; p=0.001) and cortical perfusion (r=0.53; p=0.01). In conclusion, aging, independent of other cardiometabolic risk factors, is associated with elevated circulating levels of uEVs in older adults. Circulating uEVs may serve as a biomarker of age-related changes in renal function and disease risk. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Garcia et al. (Fri,) studied this question.