Clinical trial NCT04407481: PErfusioN, OxyGen ConsUmptIon and ENergetics in ADPKD (PENGUIN)
Official title: PENGUIN: PErfusioN, OxyGen ConsUmptIon and ENergetics in ADPKD
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Polycystic Kidney Disease, Adult
Polycystic Kidney, Autosomal Dominant
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2020-05-29
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: 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.

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Renal oxygen consumption
timeFrame: 30 minutes
measure: Insulin Sensitivity
timeFrame: 4.5 hours
Secondary outcomes:
measure: Mitochondrial Function
timeFrame: 5 minutes
measure: Mitochondrial Function
timeFrame: 5 minutes
measure: Mitochondrial Function
timeFrame: 5 minutes
measure: Mitochondrial Function
timeFrame: 5 minutes
measure: Glomerular Filtration Rate (GFR)
timeFrame: 3 hours
measure: Effective Renal Plasma Flow (ERPF)
timeFrame: 2.5 hours
measure: Renin-Angiotensin-Aldosterone-System Activity
timeFrame: 5 minutes
measure: Renin-Angiotensin-Aldosterone-System Activity
timeFrame: 5 minutes
measure: Renin-Angiotensin-Aldosterone-System Activity
timeFrame: 5 minutes
measure: Kidney Injury Biomarkers
timeFrame: 5 minutes
measure: Kidney Injury Biomarkers
timeFrame: 5 minutes
measure: Kidney Injury Biomarkers
timeFrame: 5 minutes
measure: Kidney Injury Biomarkers
timeFrame: 5 minutes
measure: Kidney Injury Biomarkers
timeFrame: 5 minutes
measure: Kidney Injury Biomarkers
timeFrame: 5 minutes
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
References: