Kidney Week

Abstract: SA-PO514

Assessment of Endocannabinoid System as a Biomarker for Progression of ADPKD

Session Information

• ADPKD: Clinical Studies
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidney

• 1001 Genetic Diseases of the Kidney: Cystic

Authors

• Sempio, Cristina, University of Colorado Denver, Aurora, Colorado, United States

Cristina Sempio,

• Klawitter, Jost, University of Colorado Denver, Aurora, Colorado, United States

Jost Klawitter,

• Christians, Uwe, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado, United States

Uwe Christians,

• Chonchol, Michel, University of Colorado Denver, Aurora, Colorado, United States

Michel Chonchol,

• Cadnapaphornchai, Melissa A., Rocky Mountain Pediatric Kidney Center, Rocky Mountain Hospital for Children at Presbyterian St. Luke's Medical Center, Denver, Colorado, United States

Melissa A. Cadnapaphornchai,

• Gitomer, Berenice Y., Div. Renal Diseases and Hypertension,, Aurora, Colorado, United States

Berenice Y. Gitomer,

• Klawitter, Jelena, University of Colorado Denver, Aurora, Colorado, United States

Jelena Klawitter,

Background

Endocannabinoids (eCBs) are endogenous lipid ligands of the cannabinoid-1 receptor (CB1). In the renal vasculature, CB1 is involved in the regulation of renal blood flow and hemodynamics via NO release. Expression of CB1 and main eCBs are significantly increased in the fibrotic kidney where they modulate inflammation and fibrosis, another pathophysiological mechanism of autosomal dominant polycystic kidney disease (ADPKD).

Methods

Plasma from children and young adults with ADPKD and normal renal function were collected during an interventional trial at 0, 18 and 36 months. A single serum sample from adult ADPKD patients was collected at baseline of a cross-sectional trial (n=71, eGFR >60 mL/min per 1.73m²). All patients had available measures of total kidney volume (normalized to height (HtTKV) in pediatric patients or to body surface area (TKV/BSA) in adult patients) and left ventricular mass index (LVMI). Analysis of fourteen eCBs was performed using a liquid chromatography tandem mass spectrometry with online extraction. Statistical analysis was performed using SPSS v. 24.

Results

In children and young adults, plasma AEA (n=118, cross-sectional) correlated with HtTKV. The association was independent of the treatment group but highly dependent on child’s age. After control for age and sex, linoeyl ethanolamide was positively correlated with HtTKV and cardiovascular LVMI.
In 11 placebo treated pediatric patients with available samples at 0 and 36 months, the change in concentration of O-arachidonoyl ethanolamide positively correlated with ΔHtTKV (r=0.659) adjusted for age and sex.
In adult ADPKD patients, plasma palmitoyl- (r=0.379) and stearoyl-ethanolamide (r=0.426) positively correlated with TKV/BSA, after control for age and sex. AEA also increased with disease progression; significant negative correlation between the renal function as measured by eGFR and AEA (r=-0.395) was observed.

Conclusion

Our results showed that an overall increase of the circulating endocannabinoids is present in patients with ADPKD, with manifestations already present early in the disease, in children with ADPKD and normal kidney function. Thus, eCBs should be evaluated for their potential as biomarkers of ADPKD severity and progression and in mechanistic studies evaluating CB1’s role in mediating renal fibrosis.

Funding

• NIDDK Support