PErfusioN, OxyGen ConsUmptIon and ENergetics in ADPKD (PENGUIN)

Polycystic Kidney, Autosomal Dominant Clinical Trial

— PENGUIN  

Official title:

PENGUIN: PErfusioN, OxyGen ConsUmptIon and ENergetics in ADPKD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04407481
• Other study ID #: 20-0277
• Status: Completed
• Start date: November 1, 2020
• Est. completion date: October 13, 2022

Study information

• Verified date: February 2023
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 13, 2022
• Est. primary completion date: October 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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)

Related Conditions & MeSH terms

• Kidney Diseases
• Polycystic Kidney Disease, Adult
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug:
• Aminohippurate Sodium Inj 20%
Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)
• Iohexol Inj 300 milligrams per milliliter (MG/ML)
Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

Radiation:
• PET/CT Scan
Imaging used to visualize the kidneys and quantify renal metabolic activity

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal oxygen consumption	11-C Acetate PET/CT	30 minutes
Primary	Insulin Sensitivity	Hyperinsulinemic-Euglycemic Clamp	4.5 hours
Secondary	Mitochondrial Function	Blood draw for mitochondrial DNA copy number	5 minutes
Secondary	Mitochondrial Function	Blood draw for untargeted metabolite assessment of the tricyclic acid (TCA) cycle	5 minutes
Secondary	Mitochondrial Function	Blood draw for targeted assessment and quantification of glucose oxidation using an established metabolite panel	5 minutes
Secondary	Mitochondrial Function	Blood draw for untargeted metabolite assessment of Free Fatty Acid (FFA) oxidation	5 minutes
Secondary	Glomerular Filtration Rate (GFR)	Iohexol Clearance Study	3 hours
Secondary	Effective Renal Plasma Flow (ERPF)	PAH Clearance Study	2.5 hours
Secondary	Renin-Angiotensin-Aldosterone-System Activity	Blood draw for Plasma Renin levels	5 minutes
Secondary	Renin-Angiotensin-Aldosterone-System Activity	Blood draw for Angiotensin II levels	5 minutes
Secondary	Renin-Angiotensin-Aldosterone-System Activity	Blood draw for Copeptin levels	5 minutes
Secondary	Kidney Injury Biomarkers	Chitinase-3-like protein 1 (YKL-40) levels	5 minutes
Secondary	Kidney Injury Biomarkers	Blood draw for Neutrophil gelatinase-associated lipocalin (NGAL) levels	5 minutes
Secondary	Kidney Injury Biomarkers	Blood draw for Kidney Injury Molecule 1 (KIM-1) levels	5 minutes
Secondary	Kidney Injury Biomarkers	Blood draw for Interleukin-18 (IL-18) levels	5 minutes
Secondary	Kidney Injury Biomarkers	Blood draw for Tumor Necrosis Factor Receptor 1/2 (TNF-R 1/2) levels	5 minutes
Secondary	Kidney Injury Biomarkers	Blood draw for monocyte chemoattractant protein-1 (MCP-1) levels	5 minutes