a study to evaluate homocysteine metabolism and endothelial function in adpkd

Conditions: Autosomal Dominant Polycystic Kidney Disease

Summary: the purpose of this study is to assess homocysteine metabolism and systemic 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 estimate renal disease severity and progression in patients with early autosomal dominant polycystic kidney disease (adpkd).

adpkd is a devastating systemic disorder characterized by progressive development and enlargement of bilateral renal cysts, often leading to renal failure. disease severity and progression vary widely among patients. large phenotypic variability, incomplete understanding of underlying mechanisms, and lack of suitable biomarkers challenge potential therapies' identification, implementation, and evaluation. in adpkd, systemic endothelial dysfunction (ed), characterized by an imbalance between vasodilating (particularly nitric oxide, no) and vasoconstricting substances, develops early and correlates with renal disease severity. it has been previously associated with decreased no availability, but no abnormalities' mechanisms are still poorly understood. endothelium-dependent, no-mediated vasodilation is impaired in subjects with hyperhomocysteinemia, suggesting that no availability is decreased in these subjects. increased plasma levels of homocysteine have been reported in patients with adpkd and preserved kidney function, likely contributing to a reduction in no bioavailability. the mechanisms underlying increased homocysteine in adpkd are not known. furthermore, whether systemic endothelial function and injury or homocysteine levels can predict renal disease severity and progression in patients is unknown. the investigators' broad objective is to assess homocysteine metabolism and systemic 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 estimate renal disease severity and progression in patients with early adpkd. participants in this study will have a blood and a urine sample collected to determine biomarkers of oxidative stress, endothelial function and injury, homocysteine, and related metabolite levels. in addition, peripheral arterial tonometry (pat) will determine systemic endothelial function, and an abdominal mri will be performed to determine the patient's total kidney volume (tkv).

Eligibility criteria:
inclusion criteria: * male and female subjects, 15-40 years of age, inclusive * previous diagnosis of adpkd (based on ravine et al. criteria) * class 1 according to imaging classification * estimated gfr\>70 ml/min/1.73m\^2(ckd-epi) * ability to provide written, informed consent. exclusion criteria: * class 2 according to imaging classification * a concomitant systemic disease affecting the kidney * diabetes mellitus * predicted urine protein excretion in urinalysis \>1 g/24 hrs * subjects having contraindications to or interference with mri assessments * patients that are part of an interventional study or taking tolvaptan * female subjects that are pregnant

Keywords: autosomal dominant polycystic kidney disease (adpkd) endothelial function endothelial dysfunction homocysteine metabolism oxidative stress nadph oxidase 4 (nox4)