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.

Inclusion Criteria (all subjects):

• Provide signed and dated informed consent
• Willing to comply with all study procedures and be available for the duration of the study
• Male or female, aged 18 to 65
• Negative quantitative human chorionic gonadotropin (hCG) blood test (for women of child-bearing age only)

For healthy subjects:

• Normal liver functions tests (LFTs) as defined by the University of North Carolina (UNC) hospital laboratory reference range [aspartate aminotransferase (AST)14-38 U/L, alanine aminotransferase (ALT) 15-48 U/L, alkaline phosphatase 38-126 U/L]
• Normal clinical laboratory results including kidney function (serum creatinine) and lipid panel as reviewed by the study physician

For subjects with ADPKD:

• Man or woman between the ages of 18 and 65 with documented ADPKD

For subjects with non-ADPKD renal disease:

• Man or woman between the ages of 18 and 65 with documented non-ADPKD renal disease as determined by the study physician

Exclusion Criteria:

All Participants:

• Donation of blood within the last 30 days
• Diagnosis of human immunodeficiency virus (HIV) and/or untreated hepatitis C virus (HCV)
• History of significant alcohol abuse and/or illicit drug use
• More than 1 glass of wine or 2 beers (or equivalent in % alcohol) per day during the 48 hours prior to study and/or screening visit
• Inability to fast for 8 hours prior to study and screening sample collection
• Women who are pregnant, trying to become pregnant, or breastfeeding
• Current or recent (within 30 days) use of bile acid sequestrants, bile acid derivatives (i.e. ursodiol) or fibric acid derivatives
• History of diabetes or taking blood glucose lowering treatments
• Radiologic imaging consistent with cirrhosis and portal hypertension
• Evidence of decompensated liver disease defined as any of the following: serum albumin <3.2 g/dL, total bilirubin > 1.5 mg/dL, or prothrombin time (PT)/international normalized ratio (INR) > 1.3 times normal at screening, or history or presence of ascites, encephalopathy, or bleeding from esophageal varices
• Estimated glomerular filtration rate (GFR)< 15 mL/min per 1.73 m2, or on dialysis, at screening
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications (including inhaled) within 14 days of study visit. Corticosteroids with minimal systemic absorption (for example topical) and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease provided the dose has been stable for ≥4 weeks and is not expected to change during the course of the study.
• Primary, secondary or extra-hepatic malignancy
• BMI > 35 kg/m2 at screening
• Inability or unwillingness to give informed consent or abide by the study protocol
• History or other evidence of illness, any gastrointestinal surgery (e.g., gall bladder removal), or any other conditions or drug therapies that would make the patient, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, coronary artery disease, gall bladder disease, active gastrointestinal conditions or taking drugs known to interfere with bile acid synthesis or metabolism or the metabolism/transport of other drugs)

Healthy Subjects:

• Taking concomitant medications, both prescription and non-prescription (including herbal products and over-the-counter medications), other than oral contraceptives and multivitamins (women stabilized on hormonal methods of birth control will be allowed to participate)
• History or other evidence of liver, gall bladder, or intestinal disease in the opinion of the study investigators
• BMI > 35 kg/m2 at screening.

Subjects with non-ADPKD renal disease:

• ADPKD
• Proteinuria of ≥3 grams per day of protein into the urine; or on a single spot urine collection, the presence of ≥2 grams of protein per gram of urine creatinine (i.e., excluding patients with nephrotic-range proteinuria)
• Diabetic nephropathy patients

Healthy vs. ADPKD vs. non-ADPKD renal disease subjects