Kidney Week

Abstract: FR-PO149

Nephron Loss Reduces Excretion of Urinary Extracellular Vesicles

Session Information

• Molecular Mechanisms of CKD - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1903 CKD (Non-Dialysis): Mechanisms

Authors

• Blijdorp, Charles J., Erasmus Medical Center, Rotterdam, Netherlands

Charles J. Blijdorp,

• Hartjes, Thomas, Erasmus Medical Center, Rotterdam, Netherlands

Thomas Hartjes,

• Kramers, Bart J., Harvard, Groningen, Netherlands

Bart J. Kramers,

• Van royen, Martin E., Erasmus Medical Center, Rotterdam, Netherlands

Martin E. Van royen,

• Gansevoort, Ron T., University Medical Center Groningen, Groningen, Netherlands

Ron T. Gansevoort,

• Zietse, Robert, Erasmus Medical Center, Rotterdam, Netherlands

Robert Zietse,

• Hoorn, Ewout J., Erasmus Medical Center, Rotterdam, Netherlands

Ewout J. Hoorn,

Background

Urinary extracellular vesicles (uEVs) are emerging as non-invasive biomarkers for various kidney diseases. We previously showed that the uEV-marker CD9 decreases with disease progression in autosomal dominant polycystic kidney disease (ADPKD; Salih et al., J Am Soc Nephrol 2016). Therefore, here, we hypothesize that nephron loss decreases uEV excretion.

Methods

We quantified uEVs in two different settings of nephron loss, including donor nephrectomy and ADPKD with progressive decline of estimated glomerular filtration rate (eGFR). We obtained spot and 24-hour urine samples from 20 kidney donors the day prior and 3 months after nephrectomy, and from 27 ADPKD patients at baseline and after a median follow-up time of 3 years. uEVs were quantified using 3 techniques, including EVQuant (a novel technique which counts individual fluorescently labeled EVs after immobilization in a matrix), nanoparticle tracking analysis (NTA), and a time-resolved fluorescence immunoassay (TRFIA) capturing CD9+ uEVs.

Results

Baseline kidney function correlated with uEV excretion in both healthy donors (EVQuant vs. eGFR: R² 0.41, P = 0.01) and ADPKD patients (CD9-TRFIA vs. mGFR: R² 0.23, P = 0.02). Donor nephrectomy reduced eGFR by 32 ml/min/1.73m² or 38% after 3 months. uEV excretion decreased by 18% as analyzed by EVQuant (95%CI: 6-31%), 21% by NTA (95%CI: 7-34%) and 22% by TRFIA (95%CI: 3-42%). In the ADPKD cohort the average loss in eGFR was 4.1 ml/min/1.73m²/year (95%CI 2.9-5.2), or 18% after 3 years (95%CI 13-23%). In this period, the number of uEVs reduced by 22% (95%CI: 9-36%, as analyzed by TRFIA).

Conclusion

Nephron loss reduces uEV excretion both after donor nephrectomy and in progressive ADPKD. Therefore, it is important to adjust for uEV excretion when performing cross-sectional or longitudinal analyses of uEVs in patients with reduced kidney function.