PErfusioN, OxyGen ConsUmptIon and ENergetics in ADPKD (PENGUIN)
Condition: Polycystic Kidney Disease, Adult; Polycystic Kidney, Autosomal Dominant
MeSH terms: Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
Study type: Observational

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.
    


Intervention name(s): Aminohippurate Sodium Inj 20%; Iohexol Inj 300 milligrams per milliliter (MG/ML); PET/CT Scan
Intervention type(s): Drug; Drug; Radiation
Intervention description(s): Diagnostic aid/agent used to measure effective renal plasma flow (ERPF); Diagnostic aid/agent used to measure glomerular filtration rate (GFR); Imaging used to visualize the kidneys and quantify renal metabolic activity
Other intervention name(s): •- Sodium 4-amino hippurate (PAH) inj 20% 2g/10 milliliter (mL) • Para-aminohippurate • Aminohippuric acid; omnipaque 300
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.
      
Biospecimen description: 
      During the study, we will collect blood and urine samples for assessment of kidney function
      and kidney injury markers.