PErfusioN, OxyGen ConsUmptIon and ENergetics in ADPKD (PENGUIN)

Completed

• Conditions: Polycystic Kidney Disease, Adult; Polycystic Kidney, Autosomal Dominant
• Interventions: Drug: Aminohippurate Sodium Inj 20%; Drug: Iohexol Inj 300 milligrams per milliliter (MG/ML); Radiation: PET/CT Scan

• Registration Number: NCT04407481
• Lead Sponsor: University of Colorado, Denver

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-05-19
• Study First Submitted QC: 2020-05-27
• Study First Posted: 2020-05-29
• Study Start: 2020-11-01
• Primary Completion: 2022-10-13
• Study Completion: 2022-10-13
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-01
• Last Update Posted: 2023-02-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

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

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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)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Adults with autosomal dominant polycystic kidney disease	Iohexol Inj 300 milligrams per milliliter (MG/ML)	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).
Adults with autosomal dominant polycystic kidney disease	PET/CT Scan	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).
Adults with autosomal dominant polycystic kidney disease	Aminohippurate Sodium Inj 20%	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).

Primary Outcome Measures

Name	Time	Method
Renal oxygen consumption	30 minutes	11-C Acetate PET/CT
Insulin Sensitivity	4.5 hours	Hyperinsulinemic-Euglycemic Clamp

Secondary Outcome Measures

Name	Time	Method
Renin-Angiotensin-Aldosterone-System Activity	5 minutes	Blood draw for Copeptin levels
Kidney Injury Biomarkers	5 minutes	Blood draw for monocyte chemoattractant protein-1 (MCP-1) levels
Glomerular Filtration Rate (GFR)	3 hours	Iohexol Clearance Study
Effective Renal Plasma Flow (ERPF)	2.5 hours	PAH Clearance Study
Mitochondrial Function	5 minutes	Blood draw for untargeted metabolite assessment of Free Fatty Acid (FFA) oxidation

Trial Locations

Locations (1)

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States