MEMRI and Kidney Disease

University of Edinburgh120 enrolled

Overview

Acute kidney injury (AKI) is common and costly.1 Although patients who suffer an episode of AKI may recover, many will go on to develop cardiovascular disease and chronic kidney disease (CKD). Cardiovascular disease is an important complication of AKI.2 Similar to AKI, CKD and kidney transplantation and kidney donation associations with cardiovascular disease.1 The risk of cardiovascular disease complications is also increased in patients with inflammatory diseases that affect the kidneys, such as vasculitis. Currently, there are no reliable biomarkers that will identify those patients with kidney disease that will go on to develop cardiovascular disease. This study will explore the potential of manganese-enhanced magnetic resonance imaging (MEMRI) to act as a biomarker of AKI and its cardiovascular and renal complications. An analogue of calcium, manganese is readily taken-up into viable cells where it increases T1 relaxivity. Preliminary data show rapid manganese uptake in the heart and kidneys of healthy subjects. The investigators propose to use MEMRI to demonstrate differences in renal and myocardial calcium handling in patients with acute insults (such as AKI, transplant rejection, donation or episodes of rejection or new vasculitis presentations) or improvements (such as transplantation). The investigators will also investigate whether these abnormalities reverse in those whose injury resolves or persist in those who clearly develop CKD, or who are at risk of future cardiovascular disease and CKD.

Study Type

OBSERVATIONAL

Enrollment

120

Conditions

Acute Kidney Injury Kidney Transplant Vasculitis

Interventions

MRIDIAGNOSTIC_TEST

MRI imaging of the kidney and heart with an intravenous infusion of manganese dipyridoxl diphosphate (Mangafodipir, MnDPDP).

Blood testsDIAGNOSTIC_TEST

full blood count, urea and electrolytes, liver function test, CRP, biomarkers for endothelial function, storage of serum and plasma for future analyses.

Urine testsDIAGNOSTIC_TEST

Urine protein, Urine creatinine

Cardiovascular analysisDIAGNOSTIC_TEST

24 hour blood pressure, arterial stiffness

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: All subjects to be entered must: Be able to provide written informed consent after having received oral and written information about the study. \>18 years of age Availability to complete study visits If female, be non-pregnant as evidenced by a negative pregnancy test or be post-menopausal or surgically sterile. Additionally, cohort specific inclusion criteria are as follows: Cohort 1; Acute kidney injury- A diagnosis of AKI will be made based on the following criteria (based on the definition used in the Kidney Precision Medicine Project www.kpmp.org): Previous (within 3 years) eGFR \>45 ml/min/1.73m2 OR no history of kidney disease if no blood results available AND Elevated creatinine \>1.5x previous result OR \>150 μmol/L if no previous value AND Increasing creatinine within 48 hours OR requirement for dialysis. Cohort 2; Chronic kidney disease- Stable CKD for at least 6 months (monitored by eGFR), matched to AKI cohort at follow up based on renal function. Cohort 3: Matched controls- Matched to AKI cohort participants at baseline for age, sex, cardiovascular disease risk and cardiovascular medication. Cohort 4; Vasculitis- A new diagnosis of vasculitis or an existing diagnosis with relapsing disease, and kidney involvement. Cohort 5; Kidney transplantation- Has kidney failure and has received a kidney transplant in the preceding 1 month. Cohort 6: Kidney transplant rejection- Biopsy proven episode of transplant rejection. Exclusion Criteria: The following criteria apply to all patients: 1. Unable to give informed consent. 2. Have any contraindications to standard MRI safety criteria, including implanted devices. 3. Subjects under the age of 18 years old. 4. Pregnancy/positive pregnancy test. 5. Current breastfeeding. 6. Have a diagnosis of kidney disease due to polycystic kidney disease. 7. Patients in critical care or on surgical wards will be excluded. 8. Patients taking calcium channel antagonists or digoxin. Additionally, cohort specific exclusion criteria are as follow: Cohort 1- Excluded if they have a diagnosis of diabetes. Cohort 2- Excluded if receiving dialysis or those with a functional kidney transplant, multi-system disorders (e.g., systemic vasculitis), or any patients receiving immunosuppression.

Outcomes

Primary Outcomes

Manganese Uptake (Ki)

Rate of manganese uptake in the kidney (cortex and medulla) and myocardium

Time frame: (baseline and follow up scan in relevant cohorts)

Secondary Outcomes

24 hour blood pressure

Time frame: baseline and follow up

Arterial stiffness.

Measure of arterial stiffness

Time frame: baseline and follow up

Biomarkers of endothelial function

Time frame: baseline and follow up

MEMRI and Kidney Disease

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts