MEMRI and Kidney Disease

Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) in Patients With Kidney Disease

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 Overview

• Status: Recruiting
• Conditions: Vasculitis; Acute Kidney Injury; Kidney Transplant; Chronic Kidney Disease(CKD)
• Intervention / Treatment: Diagnostic test: MRI; Diagnostic test: Blood tests; Diagnostic test: Urine tests; Diagnostic test: Cardiovascular analysis

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Hannah Preston, MBCHb; Phone Number: 447889742171; Email: v1hprest@ed.ac.uk
• Study Contact Backup: Name: Neeraj Dhaun; Email: bean.dhaun@ed.ac.uk

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom
    • Recruiting
    • NHS Lothian
    • Contact: Neeraj Dhaun, MBChB; Email: bean.dhaun@ed.ac.uk
    • Contact: Hannah Preston, MBCHb; Phone Number: 447889742171; Email: v1hprest@ed.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Cohort 1- Acute Kidney Injury- 20 patients with acute kidney injury (AKI). AKI diagnosis will be based on clinical and biochemical data reflecting KDIGO criteria.

Cohort 2- Chronic Kidney disease (CKD)- 20 age- and sex-matched patients with CKD will be recruited and the patients' eGFR will be matched to that of patients who had AKI and developed persistent renal impairment at the time of their interval scan (3-6 months from their baseline scan).

Cohort 3- Control subjects- 20 age-, sex- and cardiovascular risk factor- matched control subjects will be recruited and matched to the AKI cohort.

Cohort 4- Vasculitis- 20 patients with a new diagnosis of vasculitis (or an existing diagnosis with relapsing disease), and kidney involvement.

Cohort 5- Kidney failure undergoing transplantation.- 20 patients with kidney failure and will receive a kidney transplant in the following 1 month.

Cohort 6- Kidney transplant rejection- 20 patients with a biopsy proven diagnosis of transplant

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acute Kidney Injury; 20 patients with acute kidney injury (AKI). AKI diagnosis will be based on clinical and biochemical data reflecting KDIGO criteria.	Diagnostic test: MRI; MRI imaging of the kidney and heart with an intravenous infusion of manganese dipyridoxl diphosphate (Mangafodipir, MnDPDP).; Diagnostic test: Blood tests; full blood count, urea and electrolytes, liver function test, CRP, biomarkers for endothelial function, storage of serum and plasma for future analyses.; Diagnostic test: Urine tests; Urine protein, Urine creatinine; Diagnostic test: Cardiovascular analysis; 24 hour blood pressure, arterial stiffness
Chronic Kidney Disease; 20 age- and sex-matched patients with CKD will be recruited and the patients' eGFR will be matched to that of patients who had AKI and developed persistent renal impairment at the time of their interval scan (3-6 months from their baseline scan).	Diagnostic test: MRI; MRI imaging of the kidney and heart with an intravenous infusion of manganese dipyridoxl diphosphate (Mangafodipir, MnDPDP).; Diagnostic test: Blood tests; full blood count, urea and electrolytes, liver function test, CRP, biomarkers for endothelial function, storage of serum and plasma for future analyses.; Diagnostic test: Urine tests; Urine protein, Urine creatinine; Diagnostic test: Cardiovascular analysis; 24 hour blood pressure, arterial stiffness
Control Subjects; 20 age-, sex- and cardiovascular risk factor- matched control subjects will be recruited and matched to the AKI cohort	Diagnostic test: MRI; MRI imaging of the kidney and heart with an intravenous infusion of manganese dipyridoxl diphosphate (Mangafodipir, MnDPDP).; Diagnostic test: Blood tests; full blood count, urea and electrolytes, liver function test, CRP, biomarkers for endothelial function, storage of serum and plasma for future analyses.; Diagnostic test: Urine tests; Urine protein, Urine creatinine; Diagnostic test: Cardiovascular analysis; 24 hour blood pressure, arterial stiffness
Vasculitis; 20 patients with a new diagnosis of vasculitis (or an existing diagnosis with relapsing disease), and kidney involvement	Diagnostic test: MRI; MRI imaging of the kidney and heart with an intravenous infusion of manganese dipyridoxl diphosphate (Mangafodipir, MnDPDP).; Diagnostic test: Blood tests; full blood count, urea and electrolytes, liver function test, CRP, biomarkers for endothelial function, storage of serum and plasma for future analyses.; Diagnostic test: Urine tests; Urine protein, Urine creatinine; Diagnostic test: Cardiovascular analysis; 24 hour blood pressure, arterial stiffness
Kidney transplant rejection; 20 patients with a biopsy proven diagnosis of transplant rejection	Diagnostic test: MRI; MRI imaging of the kidney and heart with an intravenous infusion of manganese dipyridoxl diphosphate (Mangafodipir, MnDPDP).; Diagnostic test: Blood tests; full blood count, urea and electrolytes, liver function test, CRP, biomarkers for endothelial function, storage of serum and plasma for future analyses.; Diagnostic test: Urine tests; Urine protein, Urine creatinine; Diagnostic test: Cardiovascular analysis; 24 hour blood pressure, arterial stiffness
Kidney failure undergoing transplantation; 20 patients with kidney failure and will receive a kidney transplant in 1 month	Diagnostic test: MRI; MRI imaging of the kidney and heart with an intravenous infusion of manganese dipyridoxl diphosphate (Mangafodipir, MnDPDP).; Diagnostic test: Blood tests; full blood count, urea and electrolytes, liver function test, CRP, biomarkers for endothelial function, storage of serum and plasma for future analyses.; Diagnostic test: Urine tests; Urine protein, Urine creatinine; Diagnostic test: Cardiovascular analysis; 24 hour blood pressure, arterial stiffness

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Manganese Uptake (Ki)	Rate of manganese uptake in the kidney (cortex and medulla) and myocardium	(baseline and follow up scan in relevant cohorts)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24 hour blood pressure		baseline and follow up
Arterial stiffness.	Measure of arterial stiffness	baseline and follow up
Biomarkers of endothelial function		baseline and follow up

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: NHS Lothian

Publications and helpful links

General Publications

• Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet. 2012 Aug 25;380(9843):756-66. doi: 10.1016/S0140-6736(11)61454-2. Epub 2012 May 21.
• Legrand M, Rossignol P. Cardiovascular Consequences of Acute Kidney Injury. N Engl J Med. 2020 Jun 4;382(23):2238-2247. doi: 10.1056/NEJMra1916393. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2024
• Primary Completion (Estimated): November 7, 2029
• Study Completion (Estimated): November 7, 2029

Study Registration Dates

• First Submitted: November 18, 2024
• First Submitted That Met QC Criteria: November 18, 2024
• First Posted (Actual): November 21, 2024

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: kidney disease; MEMRI; manganese enhanced magnetic resonance imaging; Manganese enhanced MRI
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Acute Kidney Injury; Kidney Diseases; Renal Insufficiency, Chronic; Vasculitis; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Urological; Clinical Chemistry Tests; Hematologic Tests; Urinalysis
• Other Study ID Numbers: 23/WA/0276

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Anonymised data after the end of the study will be disseminated in the public domain through the form of publications. Raw data will be retained within the study team and those researchers who will be continuing the study or further expanding the use of MEMRI will have access to this data. Anonymised data will be shared with external collaborators and scientists, subject to governance approvals.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No