Application of Functional Renal MRI to Improve Assessment of Chronic Kidney Disease

Study Overview
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Brief Summary
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Research question: Can multiparametric renal Magnetic Resonance Imaging (MRI) provide structural and functional assessment of the kidneys to deliver prognostic information and guide treatment options in chronic kidney disease (CKD)? Aims and objectives: To establish a multiparametric renal MRI protocol in CKD cohorts. To use multiparametric MRI to characterise people with and without CKD progression. To compare multiparametric renal MRI with 'gold-standard' renal biopsy to determine pathological processes of CKD progression that are detectable by MRI.

Detailed Description
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The study will have three stages. Stage 1: 45 people with CKD from nine UKRIN centres will undergo multiparametric MRI to test patient tolerance, data completeness and central data collection processes. Stage 2: A multicentre, prospective cohort study of 450 people with CKD, collecting multiparametric renal MRI at baseline and 2 years. Long-term outcomes will be determined with efficient tracking of kidney failure events via the UK Renal Registry at 5 and 10 years. Stage 3: A mechanistic sub-study of 45 patients (from Stage 2) who have had a routine renal biopsy. Detailed comparisons will be made between multiparametric MRI and histopathological changes. Tissue blocks will undergo quantitative analysis of fibrosis, capillary density and inflammation using immunohistochemistry techniques.

Official Title
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Application of Functional Renal MRI to Improve Assessment of Chronic Kidney Disease

Conditions
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Chronic Kidney Diseases

Intervention / Treatment
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* Diagnostic Test: Multiparametric renal MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age 18-75 years CKD category G3-4 or CKD category G1-2 with overt albuminuria (urine ACR>30mg/mmol) Capable of giving informed consent Exclusion Criteria Autosomal dominant polycystic kidney disease (ADPKD) Glomerulonephritis (GN) actively receiving immunosuppression, or within the preceding 90 days. Multiple myeloma (MM) Acute Kidney Injury (AKI) within the preceding 90 days Solid organ transplant Known single kidney Contraindications to MRI (e.g. permanent pacemaker, metallic foreign bodies, claustrophobia etc.)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Main study cohort<br>Patients with CKD recruited from specialist nephrology clinics | Diagnostic Test: Multiparametric renal MRI<br>* Localiser scans; Kidney volume; Longitudinal (T1) relaxation time mapping; Diffusion weighted imaging (DWI); Phase Contrast MRI; Arterial spin labelling (ASL); Blood Oxygen Level Dependent (BOLD) mapping<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CKD progression | kidney failure (doubling of serum creatinine, eGFR<15ml/min or RRT) OR a 40% decline in eGFR | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney failure events | Doubling of serum creatinine, eGFR<15ml/min or RRT | 10 years | 
| 40% decline in eGFR from baseline |  | 10 years | 
| eGFR trajectory | (ml/min/yr) | 2 years | 
| AKI events | AKI as per KDIGO serum creatinine criteria | 4 years | 
| Cardiovascular events |  | 4 years | 
| All cause mortality |  | 10 years |