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Abstract: INFO28

Role of Homocysteine Metabolism, Endothelial Function, and Microvascular Rarefaction on Renal Disease Severity and Progression in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Session Information

  • Informational Posters
    November 04, 2021 | Location: On-Demand, Virtual Only
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • No subcategory defined

Authors

  • Eirin, Alfonso, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Hogan, Marie C., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Chebib, Fouad T., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Harris, Peter C., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Torres, Vicente E., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Irazabal, Maria V., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
Description

ADPKD is a devastating systemic disorder characterized by progressive development and enlargement of bilateral renal cysts leading to renal failure. Disease severity and progression vary widely among patients. Large phenotypic variability, incomplete understanding of underlying mechanisms, and lack of promising biomarkers challenge potential therapies’ identification, implementation, and evaluation. In ADPKD, endothelial dysfunction (ED), characterized by an imbalance between vasodilating (particularly nitric oxide, NO) and vasoconstricting substances, develops early and correlates with renal disease severity. We propose that preservation of endothelial function will ameliorate renal disease severity and progression. Increased homocysteine has been reported in patients with ADPKD, even in those with preserved kidney function. Homocysteine decreases NO availability. However, the mechanisms underlying increased homocysteine in ADPKD are not known. The purpose of this study is to assess homocysteine metabolism and endothelial function at the early stages of the disease and determine the prognostic value of homocysteine, related metabolites, and markers of endothelial function and injury to assess renal disease severity and progression in patients with early ADPKD. This is a prospective longitudinal study and will include male and female, young (18-40-years) well-characterized patients with early (eGFR>90mL/min/1.73m2) ADPKD. Patients with different classes of disease severity will be selected using the ADPKD classification. Inclusion and exclusion criteria are presented in the table below. Subject participation includes in-person visits to Mayo Clinic Rochester. Participants will be asked to complete a health questionnaire and provide a urine sample and a blood sample at each visit. In addition, the study will include measurements of peripheral arterial tonometry (endoPAT) and an abdominal MRI without contrast at each visit. There will be a total of 3 visits, each 12 months apart. Recruitment is ongoing. The study is being funded by NIH.

Funding

  • NIDDK-NIH, 1R01DK128017-01 to MVI