This is a single center, comparative cohort study to investigate alterations in hepatic transporter function in subjects with autosomal dominant polycystic kidney disease (ADPKD) compared to healthy subjects and subjects with non-ADPKD renal disease. Eligible subjects will be 18-65 years of age and of any race/ethnicity and gender.
ADPKD is a relatively common genetic disease affecting about 1 out of every 1000 people worldwide. Progression of ADPKD is characterized by the proliferation of fluid-filled kidney cysts. Development of these cysts is progressive and can lead to end-stage renal disease and ultimately, renal failure in many patients. The most common extra-renal complication of ADPKD is the formation of liver cysts, which can vary from minor to extensive. Hepatic cysts can develop from medium-sized bile ducts and complications (i.e., cyst rupture, infection, obstruction of bile ducts, and compromised portal venous flow) can arise from increasing cystic burden. Previous studies have shown that elevated levels of endogenous molecules such as bile acids in ADPKD may indicate altered transporter function. Other endogenous molecules such as coproporphyrin (CP) I and III may be used as probes to assess hepatic transporter function. The objective of this study is to investigate and quantify ADPKD-associated alterations in endogenous molecule profiles (e.g., bile acids, CP) relative to subjects with non-ADPKD renal disease and healthy individuals, and to investigate specific hepatic transporter polymorphisms that may be related to the alterations. This is important because subjects with ADPKD may be predisposed to adverse reactions associated with some medications that require hepatic transporters for excretion. Potential study participants will be pre-screened over the phone and then scheduled for a 2-hour study visit. All urine samples within the 2-hour interval will be collected from all participants along with clinical, physical and questionnaire data. Fasting blood samples will be collected at time 0 and 120 min.
Study Type
OBSERVATIONAL
Enrollment
24
University of North Carolina
Chapel Hill, North Carolina, United States
Difference in serum coproporphyrin I and III concentrations
nmol
Time frame: 2 hours
Difference in serum and urine bile acid profiles
nmol
Time frame: 2 hours
Difference in renal clearance of coproporphyrin I and III
mL/min
Time frame: 2 hours
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