Validation of Renal Perfusion CEUS Against MRI, and Its Application in Acute Kidney Injury

The purposes of this study is 1. To establish the validity of CEUS to measure renal perfusion by comparing it against ASL-MRI in young and older healthy volunteers, and generate a normative dataset of CEUS measures of renal perfusion. 2. Establish proof of principle for the use of CEUS to measure renal perfusion in the acute phase of AKI, demonstrating its feasibility and potential clinical utility. We will do this by performing daily CEUS measurements for up to five days in a cohort of people with AKI stage 3, commencing as close to onset.

of AKI as possible, correlating with clinical data and following outcomes until 90 days.

Kidneys have an extremely high blood flow. A quarter of the blood that is pumped by the heart goes to the kidneys, and your entire blood volume passes through your kidneys forty times each day. Some of this blood flow is needed to keep the kidneys healthy by delivering oxygen and nutrients; this delivery of blood to the kidney is called 'perfusion'. We know that many forms of kidney disease involve a fall in kidney perfusion. In particular, reduced kidney perfusion is a common cause of a sudden reduction in kidney function, called Acute Kidney Injury (AKI). AKI is an extremely important problem, as people who sustain AKI are at higher risk of death, often remain in hospital for longer periods of time and sometimes experience long-term kidney damage. At the moment, there is no practical way to measure kidney perfusion in patients, and developing ways to do this would lead to ways to improve and individualise treatment.

We would like to perform a research project to test whether a new method of assessing kidney perfusion can improve care for people with AKI. A new type of ultrasound scan (contrast enhanced ultrasound, or CEUS) is available, and has a number of advantages. It is safe, does not involve radiation, and importantly for patients with AKI who are often very poorly, it can be performed at the bedside (so no need for patients to transfer to scanners). However, at the moment we do not know if CEUS is a reliable way to measure kidney perfusion.

Our research project has two stages. In the first stage, we will test whether CEUS can accurately measure renal perfusion. We will do that by comparing it with the gold standard method using MRI scanning in 20 healthy volunteers (10 young and 10 older volunteers), who will have both scans on the same day. Heathy volunteers have been chosen for two reasons: firstly, it would be too intrusive to ask patients with AKI to undergo two types of scanning on the same day; secondly using CEUS to measure renal perfusion in healthy volunteers will allow us to determine 'normal' values in younger and older people that will be useful as a comparison for future research. If CEUS proves to be a reasonable way to measure renal perfusion, we will then study if CEUS is useful in patients with AKI. We will perform CEUS in 30 patients who are in hospital and have severe AKI (stage 3 AKI). We will perform CEUS as soon as possible after the onset of AKI, and then take daily measurements for five days to determine if CEUS gives useful additional useful information in these patients. We will also compare CEUS measures with the degree to which patients' kidney function recovers at time of discharge from hospital, and then again three months later. Results from this research will pave the way for the future use of CEUS for the care of patients with kidney disease.

We would like to perform a study to test can measure kidney perfusion. We will do this by comparing CEUS with MRI scans which is the 'gold-standard' method of measuring kidney perfusion. If CEUS performs well, then this will allow future studies in which CEUS can be used to help patients with kidney disease.

Eligibility Criteria:
Stage1(healthy volunteers)

Inclusion Criteria:

* Healthy male or female aged 18 years or older and able to give informed, written consent.

Exclusion Criteria:

* estimated Globular Filtration Rate (eGFR) \<60ml/min or albuminuria

  * Diabetes
  * Prescription of anti-hypertensive agents that alter renal haemodynamics (renal angiotensin
  * Known allergy to SonoVue contrast agent
  * Contraindications to MRI

Stage2 (AKI group):

Inclusion criteria:

AKI stage 3 (as per KDIGO criteria).

Exclusion criteria:

* autosomal dominant polycystic kidney disease
* glomerulonephritis receiving immunosuppression
* multiple myeloma
* obstructive uropathy
* solid organ transplant
* known allergy to Sonvue
* lack of baseline serum creatinine value within previous 365 days -\>72hrs elapsed since detection of AKI