Polycystic Kidney Disease, Adult, Polycystic Kidney, Autosomal Dominant
Conditions
Brief summary
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of end-stage kidney disease (ESKD). The disorder is characterized by development and continued growth of multiple cysts requiring renal replacement therapy in 50% of patients by age 60 years. However, ADPKD is also a complex metabolic disorder defined by insulin resistance (IR) and mitochondrial dysfunction which may be causally related to cyst expansion, kidney function decline and contribute to reduced life expectancy. Renal hypoxia, stemming from a potential metabolic mismatch between increased renal energy expenditure and impaired substrate utilization, is proposed as a novel unifying early pathway in the development and expansion of renal cysts in ADPKD. By examining the interplay between renal O2 consumption and energy utilization in young adults with and without ADPKD, the investigators hope to identify novel therapeutic targets to impede development of cyst expansion in future trials. The investigators propose to address the specific aims in a cross-sectional study with 20 adults with ADPKD (50% female, ages 18-40 years). Comparative data will be provided from healthy adults from an ongoing study with similar study design and methods (CROCODILE Study: Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance). For this protocol, participants will complete a one day study visit at Children's Hospital Colorado. Patients will undergo a dual energy x-ray absorptiometry (DXA) to assess body composition, and a 11C-acetate positron emission tomography (PET/CT) scan to quantify renal O2 consumption. After the PET/CT, participants will undergo a hyperinsulinemic-euglycemic clamp while fasting to quantify insulin sensitivity. Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) will be measured by iohexol and PAH clearances during the hyperinsulinemic-euglycemic clamp.
Interventions
Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)
DRUGIohexol Inj 300 milligrams per milliliter (MG/ML)
Diagnostic aid/agent used to measure glomerular filtration rate (GFR)
RADIATIONPET/CT Scan
Imaging used to visualize the kidneys and quantify renal metabolic activity
Sponsors
University of Colorado, Denver
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Patients with Autosomal dominant polycystic kidney disease * Age 18-40 years * BMI \>= 18.5 and \<30 kg/m2 * Weight \<350 lbs
Exclusion criteria
* Diabetes mellitus, based on previous diagnosis * Albuminuria (≥30mg/g) or estimated glomerular filtration rate (eGFR) \<75ml/min/1.73m2 * Pregnancy or nursing * Anemia * Allergy to shellfish or iodine * Vaptan therapy (e.g. tolvaptan) * Uncontrolled hypertension (average ≥140/90 mmHg)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal oxygen consumption | 30 minutes | 11-C Acetate PET/CT |
| Insulin Sensitivity | 4.5 hours | Hyperinsulinemic-Euglycemic Clamp |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effective Renal Plasma Flow (ERPF) | 2.5 hours | PAH Clearance Study |
| Mitochondrial Function | 5 minutes | Blood draw for mitochondrial DNA copy number |
| Kidney Injury Biomarkers | 5 minutes | Chitinase-3-like protein 1 (YKL-40) levels |
| Renin-Angiotensin-Aldosterone-System Activity | 5 minutes | Blood draw for Plasma Renin levels |
| Glomerular Filtration Rate (GFR) | 3 hours | Iohexol Clearance Study |
Countries
United States
Outcome results
None listed