The Role of Endothelial Dysfunction in Adult Polycystic Kidney Disease
Condition: Polycystic Kidney, Autosomal Dominant
MeSH terms: Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
Study type: Observational

Summary: 
      This pilot study will compare endothelial function in patients with ADPKD with matched
      healthy volunteers and normotensive chronic kidney disease stage 1 & 2 patients. Patients
      will undergo a single assessment of endothelial function and measurement of plasma and urine
      levels of biomarkers of endothelial function.
    

Detailed description: 
      Following recruitment we will record the following baseline demographics; age, gender,
      smoking status, body mass index, medical history.

      Participants will undergo a noninvasive vascular assessment, venepuncture and will provide a
      urine sample.This will be done during a single visit to the CRF.

      Noninvasive vascular assessment will consist of:

        1. Peripheral Arterial Tonometry This will be measured using the EndoPAT system (Itamar
           Medical)

           Endothelial shear stress flow stimulus will be provided by inflation of a blood pressure
           cuff around the upper non-dominant arm to suprasystolic pressure (but <300mmHg) for 5
           minutes. Following release of the cuff the resulting digital microcirculation
           vasodilatory response to ischaemic hyperaemia, quantified as the pulse wave amplitude,
           will be monitored over 5 minutes. The peak pulse wave amplitude measured at 90-150s post
           cuff deflation relative to baseline will be indexed to the changes in the opposite arm
           to give the reactive hyperaemia index. This measure of endothelial function constitutes
           the outcome measure.

        2. Blood Pressure Assessment Brachial artery blood pressure will be measured in the left
           arm in the supine position using an automated device (Dinamap) and in accordance with
           the clinical research facility SOP.

        3. Blood samples and urine samples

      Samples for plasma will be centrifuged and stored at -80C. Biochemical analysis will be
      performed by the laboratory of the STH NHS Trust for standard tests and by validated assays
      for non-routine markers (as detailed below) in the Academic Nephrology Unit.

      Participants will be asked to collect a 24h urine sample from the day before the study visit
      and to provide a spot urine sample on the day. This will be analysed at the laboratory of the
      STH NHS Trust.

      Biochemical Analysis

      Serum samples will be analyzed for Full blood count, Urea, Electrolytes, Glucose, Insulin,
      Lipid Profile, Homocysteine, (Hs) CRP and Creatinine Levels.

      Serum and plasma will also be stored for future analysis of relevant biomarkers of
      endothelial function or nitric oxide metabolism as indicated by preliminary results.

      Urine samples will be analysed initially for protein creatinine ratio (PCR). The rest will be
      frozen for future analysis of urinary biomarkers of endothelial function or nitric oxide
      metabolism.
    

Intervention name(s): Peripheral (digital) arterial tonometry
Intervention type(s): Diagnostic Test
Intervention description(s): This will be measured using the EndoPAT system (Itamar Medical)
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Normotensive ADPKD patients with well preserved GFR (>60ml/min) ie those with Stage 1 or 2
        Chronic Kidney Disease recruited from a specialist PKD clinic. Healthy controls will be
        recruited matched to age, sex, body mass index (BMI) and eGFR of the ADPKD patients.