Apelin as a Potential Treatment for Chronic Kidney Disease (AlPaCKa)
Chronic Kidney Diseases, Cardiovascular Diseases, Endothelial Dysfunction
About this trial
This is an interventional basic science trial for Chronic Kidney Diseases
Eligibility Criteria
Inclusion Criteria:
- Adults >18yrs
- Stable, non-diabetic chronic kidney disease stages 1 - 4 as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 classification (estimated Glomerular Filtration Rate (eGFR) >15ml/min/1.73m2)
- Clinically optimised on an angiotensin converting enzyme inhibitor / angiotensin receptor blocker, or intolerant to these agents.
Exclusion Criteria:
- Age <18 years
- Diabetes mellitus
- Overt cardiovascular disease
- Blood pressure >160/100mmHg
- Estimated GFR of <15ml/min/1.73m2
- Renal transplant recipients
- Haemodialysis / peritoneal dialysis patients
- Serum albumin <30g/L
- Patients receiving tolvaptan therapy for polycystic kidney disease
- Patients not medically fit to attend for study visits
- Patients without mental capacity or willingness to provide informed consent
- History of multiple and/or severe allergic reaction to drugs (including study drugs) or food
- Patients who are pregnant or breast feeding
Sites / Locations
- Clinical Research Centre, Western General Hospital
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
Chronic Kidney Disease patients
Healthy volunteers
Forearm blood flow studies - acetylcholine (7.5, 15, 30microgram/min), sodium nitroprusside (1, 2, 4microgram/min) and [Pyr1]apelin-13 (0.3, 1, 3, 10, 30, 100nmol/min). Incremental doses of each lasting 8 minutes with saline washout between drugs. Renal clearance studies Two standard para-aminohippurate (PAH) / iohexol clearance studies with infusion of either apelin or placebo on each day. Dose of PAH / iohexol dependent on renal function. Continuous infusion lasting 6.5hours in total. [[Pyr1]apelin-13 infusions: 1nmol/min and 30nmol/min for 30 minutes each.
Forearm blood flow studies - acetylcholine (7.5, 15, 30microgram/min), sodium nitroprusside (1, 2, 4microgram/min) and [Pyr1]apelin-13 (0.3, 1, 3, 10, 30, 100nmol/min). Incremental doses of each lasting 8 minutes with saline washout between drugs. Renal clearance studies Two standard para-aminohippurate (PAH) / iohexol clearance studies with infusion of either apelin or placebo on each day. Dose of PAH / iohexol dependent on renal function. Continuous infusion lasting 6.5hours in total. [Pyr1]apelin-13 infusions: 1nmol/min and 30nmol/min for 30 minutes each.