Dynamic Imaging of Variation in Lupus Nephritis

Study Overview
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Brief Summary
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To use a variety of renal imaging modalities, including diffusion weighted imaging (DWI), blood oxygen level dependent (BOLD) imaging, T1rho (T1rho) imaging, and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to evaluate the intra-renal blood flow, perfusion, cellularity, fibrosis and atrophy within the kidneys of patients with lupus nephritis (LN) and compare these parameters to renal biopsy findings to determine whether DWI, BOLD, T1rho, and DCE-MRI may provide a set of non-invasive tools to assess renal function and pathology in LN.

Official Title
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Dynamic Imaging of Variation in Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Procedure: MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent agreeing to all study procedures, before any study- specific procedures are done. Male and female subjects 18 to 65 years of age, inclusive. Subjects currently being evaluated for new or recurrent LN with a SOC kidney biopsy planned OR being evaluated for IgA nephropathy and with a SOC kidney biopsy planned. Patients with LN must meet American College of Rheumatology (ACR) or Systemic Lupus Collaborating Clinics (SLICC) criteria for Systemic Lupus Erythematosus (SLE). Subjects with a life expectancy >6 months. Exclusion Criteria: Participation in another investigational study during same time period. Contraindication to receiving a GBCA. More than 2 previous lifetime exposures to a GBCA. Any contraindication to MRI, including metal implants, claustrophobia or morbid obesity. Acute or chronic severe renal insufficiency (glomerular filtration rate [GFR] <40 mL per minute per 1.73 m2). Subject requiring dialysis. Presence of pre-existing renal disease unrelated to SLE or IgA nephropathy, respectively. Acute renal insufficiency of any severity caused by the hepato-renal syndrome. Previous or pre-existing nephrogenic systemic fibrosis. History of clinically significant anti-phospholipid syndrome. Chronic liver function impairment, indicated by liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) >2-fold upper limit of normal. Platelet count <50,000/μL. Hemoglobin <8.0 g/dL. History of or presence of central nervous system (CNS) disease such as active lupus cerebritis or multiple sclerosis that might compromise blood brain barrier function. Infection that is clinically relevant, particularly hepatitis B virus (HBV), hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV). Pregnant or nursing females, or females not using effective contraception. Inability or unwillingness to return to the research site clinic for study visits at baseline and at 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Patients with Lupus Nephritis<br> | Procedure: MRI<br>* This is a multicenter, non-interventional, pilot study. Eligible subjects will have a baseline MRI of the kidney, including anatomical, DWI, BOLD, T1rho, and DCE-MRI, utilizing a macrocyclic gadolinium-based contrast agent (GBCA), followed by planned standard of care (SOC) renal biopsy and clinical laboratory assessments. Additional serum and urine will be collected from subjects at baseline for analysis of research biomarkers. Following the results of the biopsy and clinical laboratory assessments, subjects will be treated for their underlying disease at the discretion of the investigator. At 6 months, subjects will return to the clinic for a second MRI, SOC clinical and laboratory evaluation and collection of serum and urine for analysis of research biomarkers.<br>|
| Patients with IgA Neuropathy<br> | Procedure: MRI<br>* This is a multicenter, non-interventional, pilot study. Eligible subjects will have a baseline MRI of the kidney, including anatomical, DWI, BOLD, T1rho, and DCE-MRI, utilizing a macrocyclic gadolinium-based contrast agent (GBCA), followed by planned standard of care (SOC) renal biopsy and clinical laboratory assessments. Additional serum and urine will be collected from subjects at baseline for analysis of research biomarkers. Following the results of the biopsy and clinical laboratory assessments, subjects will be treated for their underlying disease at the discretion of the investigator. At 6 months, subjects will return to the clinic for a second MRI, SOC clinical and laboratory evaluation and collection of serum and urine for analysis of research biomarkers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diffusion Weight Imaging | Diffusion weighted imaging (DWI) measures ADC values that quantify the combined effects of blood microcirculation and Brownian motion of water molecules within the interstitial space. | 7 Months | 
| Blood Oxygen Level Dependent Imaging | Blood oxygen level dependent (BOLD) imaging has been widely used to analyze blood flow in various 15 and is the preferred method to detect regional differences in blood flow. | 7 Months | 
| T1rho Imaging | T1rho (T1rho) imaging is an MRI technique that is sensitive to the presence of macromolecules, such as collagen and proteoglycan 13. | 7 Months | 
| Dynamic Contrast Enhanced Magnetic Resonance Imaging | Dynamic contrast enhanced (DCE) MRI (DCE-MRI) is an imaging method where T1-weighted MRI scans are acquired dynamically after injection of an MRI contrast agent (e.g., macrocylic gadolinium). | 7 Months |