NCT06698614

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for all trials

Timeline
43mo left

Started Nov 2024

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress30%
Nov 2024Nov 2029

Study Start

First participant enrolled

November 7, 2024

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

November 18, 2024

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 21, 2024

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 7, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 7, 2029

Last Updated

December 8, 2025

Status Verified

December 1, 2025

Enrollment Period

5 years

First QC Date

November 18, 2024

Last Update Submit

December 1, 2025

Conditions

Keywords

manganese enhanced magnetic resonance imagingkidney diseaseMEMRIManganese enhanced MRI

Outcome Measures

Primary Outcomes (1)

  • Manganese Uptake (Ki)

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

    (baseline and follow up scan in relevant cohorts)

Secondary Outcomes (3)

  • 24 hour blood pressure

    baseline and follow up

  • Arterial stiffness.

    baseline and follow up

  • Biomarkers of endothelial function

    baseline and follow up

Study Arms (6)

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: MRIDiagnostic Test: Blood testsDiagnostic Test: Urine testsDiagnostic Test: Cardiovascular analysis

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: MRIDiagnostic Test: Blood testsDiagnostic Test: Urine testsDiagnostic Test: Cardiovascular analysis

Control Subjects

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

Diagnostic Test: MRIDiagnostic Test: Blood testsDiagnostic Test: Urine testsDiagnostic Test: Cardiovascular analysis

Vasculitis

20 patients with a new diagnosis of vasculitis (or an existing diagnosis with relapsing disease), and kidney involvement

Diagnostic Test: MRIDiagnostic Test: Blood testsDiagnostic Test: Urine testsDiagnostic Test: Cardiovascular analysis

Kidney failure undergoing transplantation

20 patients with kidney failure and will receive a kidney transplant in 1 month

Diagnostic Test: MRIDiagnostic Test: Blood testsDiagnostic Test: Urine testsDiagnostic Test: Cardiovascular analysis

Kidney transplant rejection

20 patients with a biopsy proven diagnosis of transplant rejection

Diagnostic Test: MRIDiagnostic Test: Blood testsDiagnostic Test: Urine testsDiagnostic Test: Cardiovascular analysis

Interventions

MRIDIAGNOSTIC_TEST

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

Acute Kidney InjuryChronic Kidney DiseaseControl SubjectsKidney failure undergoing transplantationKidney transplant rejectionVasculitis
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.

Acute Kidney InjuryChronic Kidney DiseaseControl SubjectsKidney failure undergoing transplantationKidney transplant rejectionVasculitis
Urine testsDIAGNOSTIC_TEST

Urine protein, Urine creatinine

Acute Kidney InjuryChronic Kidney DiseaseControl SubjectsKidney failure undergoing transplantationKidney transplant rejectionVasculitis

24 hour blood pressure, arterial stiffness

Acute Kidney InjuryChronic Kidney DiseaseControl SubjectsKidney failure undergoing transplantationKidney transplant rejectionVasculitis

Eligibility Criteria

Age18 Years+
Sexall
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-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

You may qualify if:

  • 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.
  • 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.

You may not qualify if:

  • The following criteria apply to all patients:
  • Unable to give informed consent.
  • Have any contraindications to standard MRI safety criteria, including implanted devices.
  • Subjects under the age of 18 years old.
  • Pregnancy/positive pregnancy test.
  • Current breastfeeding.
  • Have a diagnosis of kidney disease due to polycystic kidney disease.
  • Patients in critical care or on surgical wards will be excluded.
  • Patients taking calcium channel antagonists or digoxin.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

NHS Lothian

Edinburgh, United Kingdom

RECRUITING

Related Publications (2)

  • 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.

    PMID: 32492305BACKGROUND
  • 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.

    PMID: 22617274BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Bloods tests- FBC, renal function, liver function.

MeSH Terms

Conditions

Acute Kidney InjuryVasculitisRenal Insufficiency, ChronicKidney Diseases

Interventions

Hematologic TestsUrinalysis

Condition Hierarchy (Ancestors)

Renal InsufficiencyUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesVascular DiseasesCardiovascular DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative TechniquesClinical Chemistry TestsDiagnostic Techniques, Urological

Central Study Contacts

Hannah Preston, MBCHb

CONTACT

Neeraj Dhaun

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 18, 2024

First Posted

November 21, 2024

Study Start

November 7, 2024

Primary Completion (Estimated)

November 7, 2029

Study Completion (Estimated)

November 7, 2029

Last Updated

December 8, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

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.

Locations