PErfusioN, OxyGen ConsUmptIon and ENergetics in ADPKD (PENGUIN)

NCT ID: NCT04407481

Last Updated: 2023-02-03

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 22 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-11-01
• Study Completion Date: 2022-10-13

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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).

Aminohippurate Sodium Inj 20%

Intervention Type: DRUG

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

Iohexol Inj 300 milligrams per milliliter (MG/ML)

Intervention Type: DRUG

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

PET/CT Scan

Intervention Type: RADIATION

Imaging used to visualize the kidneys and quantify renal metabolic activity

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).

No interventions assigned to this group

Interventions

Aminohippurate Sodium Inj 20%

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

Intervention Type: DRUG

Iohexol Inj 300 milligrams per milliliter (MG/ML)

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

Intervention Type: DRUG

PET/CT Scan

Imaging used to visualize the kidneys and quantify renal metabolic activity

Intervention Type: RADIATION

Other Intervention Names

•- Sodium 4-amino hippurate (PAH) inj 20% 2g/10 milliliter (mL) • Para-aminohippurate • Aminohippuric acid; omnipaque 300

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Children's Hospital Colorado

Aurora, Colorado, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38621633 (View on PubMed)

Other Identifiers

20-0277

Identifier Type: -

Identifier Source: org_study_id