PErfusioN, OxyGen ConsUmptIon and ENergetics in ADPKD (PENGUIN)

NCT04407481 | Completed FDA Drug

• 1 other identifier: 20-0277
• Study Type: observational
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Polycystic Kidney Disease, Adult; Polycystic Kidney, Autosomal Dominant

Outcome Measures

Primary Outcomes (2)

• Renal oxygen consumption

  11-C Acetate PET/CT

  30 minutes

• Insulin Sensitivity

  Hyperinsulinemic-Euglycemic Clamp

  4.5 hours

Secondary Outcomes (15)

• Mitochondrial Function

  5 minutes

• Mitochondrial Function

  5 minutes

• Mitochondrial Function

  5 minutes

• Mitochondrial Function

  5 minutes

• Glomerular Filtration Rate (GFR)

  3 hours

Study Arms (2)

Adults with autosomal dominant polycystic kidney disease

All participants will undergo DXA scan, PET/CT using 11-C acetate to measure renal oxygen consumption, hyperinsulinemic-euglycemic clamp to quantify insulin sensitivity, and renal clearance testing using iohexol and para-aminohippurate (PAH) to quantify glomerular filtration rate (GFR) and effective renal plasma flow (ERPF).

Drug: Aminohippurate Sodium Inj 20%; Drug: Iohexol Inj 300 milligrams per milliliter (MG/ML); Radiation: PET/CT Scan

Healthy Controls

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).

Interventions

Aminohippurate Sodium Inj 20% DRUG

Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

Also known as: •- Sodium 4-amino hippurate (PAH) inj 20% 2g/10 milliliter (mL) • Para-aminohippurate • Aminohippuric acid

Adults with autosomal dominant polycystic kidney disease

Iohexol Inj 300 milligrams per milliliter (MG/ML) DRUG

Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

Also known as: omnipaque 300

Adults with autosomal dominant polycystic kidney disease

PET/CT Scan RADIATION

Imaging used to visualize the kidneys and quantify renal metabolic activity

Adults with autosomal dominant polycystic kidney disease

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• Patients with Autosomal dominant polycystic kidney disease
• Age 18-40 years
• BMI \>= 18.5 and \<30 kg/m2
• Weight \<350 lbs

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Bjornstad P, Richard G, Choi YJ, Nowak KL, Steele C, Chonchol MB, Nadeau KJ, Vigers T, Pyle L, Tommerdahl K, van Raalte DH, Hilkin A, Driscoll L, Birznieks C, Hopp K, Wang W, Edelstein C, Nelson RG, Gregory AV, Kline TL, Blondin D, Gitomer B. Kidney Energetics and Cyst Burden in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study. Am J Kidney Dis. 2024 Sep;84(3):286-297.e1. doi: 10.1053/j.ajkd.2024.02.016. Epub 2024 Apr 15.

  PMID: 38621633 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

During the study, we will collect blood and urine samples for assessment of kidney function and kidney injury markers.

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Interventions

Iohexol

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Triiodobenzoic Acids; Iodobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 29, 2020
• Study Start: November 1, 2020
• Primary Completion: October 13, 2022
• Study Completion: October 13, 2022
• Last Updated: February 3, 2023

Record last verified: 2023-02

Locations

US (1)