Abstract: FR-PO319

Elevated Circulating Homocysteine Levels Precede Hemodynamic Changes and Correlate with Disease Severity in Young Autosomal Dominant Polycystic Kidney Disease (ADPKD) Patients

Session Information

Category: Genetic Diseases of the Kidney

  • 801 Cystic Kidney Diseases

Authors

  • Chengappa, Madhuri, Mayo Clinic, Rochester, Minnesota, United States
  • Irazabal, Maria V., Mayo Clinic, Rochester, Minnesota, United States
  • Kahveci, Ali, Mayo Clinic, Rochester, Minnesota, United States
  • Edwards, Marie E., Mayo Clinic, Rochester, Minnesota, United States
  • Chebib, Fouad T., Mayo Clinic, Rochester, Minnesota, United States
  • Herrmann, Sandra, Mayo Clinic, Rochester, Minnesota, United States
  • King, Bernard F., Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Amir, Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Clinic, Rochester, Minnesota, United States
  • Torres, Vicente E., Mayo Clinic, Rochester, Minnesota, United States
Background

Vascular manifestations are the most important non-cystic complications and the main cause of death in patients with ADPKD. Endothelial dysfunction and vascular remodeling are detectable early in ADPKD, and a decrease in magnetic resonance imaging (MRI)-derive renal blood flow (RBF) has been proposed as a marker of disease severity. Homocysteine (Hcy), a precursor of hydrogen sulfide, is an established biomarker for endothelial dysfunction and vascular disease and linked to increased oxidative stress. However, whether increased circulating Hcy levels correlate with disease severity and precede hemodynamic changes in early ADPKD has not been reported.

Methods

We prospectively measured circulating levels of Hcy (LC/MS/MS) and 8-isoprostane (ELISA) in early (18-30 years, eGFR>90 mL/min/1.73 m2) normotensive (<140/90 mmHg without BP medication) ADPKD patients, and in age-matched healthy volunteers (HV) (n=10, 6F/4M each). Total kidney volume (TKV) and RBF were evaluated with MRI.

Results

Mean age was 23 years old, but TKV twofold higher in ADPKD vs. HV (Table). BP tended to be elevated in ADPKD, but eGFR, RBF, and height adjusted RBF (HtRBF) were similar between the groups (Table). Circulating levels of Hcy and 8-isoprostanes were elevated in ADPKD vs. HV (Table, Fig, p<0.05). Furthermore, Hcy and isoprostane (but not RBF) levels directly correlated with TKV and HtTKV (Fig).

Conclusion

Early ADPKD is associated with elevation in circulating Hcy and isoprostane levels, which correlate with disease severity. These findings imply that oxidative stress and endothelial dysfunction might be present before overt hemodynamic changes, and possibly contribute to disease progression. Further experiments are needed to investigate the sources of oxidative stress in patients with ADPKD.