Mediators of Loin Pain in IgA Nephropathy

Official title

LO-PAIgN: Mediators of Loin Pain in Immunoglobulin-A Nephropathy

Overview

The goal of this observational study is to learn about loin pain in people with Immunoglobulin A nephropathy (IgAN). The main question it aims to answer is: What changes occur in the kidneys, urine, and blood when people with IgAN experience loin pain? Participants will have MRI scans of their kidneys, provide urine and blood samples, and have their latest kidney function test results reviewed. For participants who experience loin pain, these assessments will be carried out during a pain episode and again when they are pain-free, so the results can be compared.

Detailed description

Some people with Immunoglobulin A nephropathy (IgAN) experience loin pain, or pain around the kidneys, but the underlying cause of this pain is not well understood. Current treatment options often do not provide effective pain relief, and a better understanding of the mechanisms involved may support the development of more targeted treatments in the future and help understand what this pain may mean for the disease state.

This observational study will investigate whether loin pain in IgAN is associated with changes in the kidneys, kidney function, and biological markers in blood and urine. Participants will undergo magnetic resonance imaging (MRI) of the kidneys to assess whether there are structural or tissue-related differences during episodes of pain compared with pain-free periods. The study will also assess the renal pelvis, the urine-collecting part of the kidney, to explore whether it may be involved in the development of pain.

Blood and urine samples will be collected to investigate whether biological molecules differ during pain episodes and pain-free periods. Urine samples will also be examined under the microscope to assess for the presence of blood cells or other features that may suggest kidney injury or inflammation.

Participants' most recent kidney function test results will also be reviewed to explore whether kidney function is associated with the presence or severity of loin pain. Together, these assessments aim to provide a better understanding of what happens in the kidneys and biological samples of people with IgAN when they experience loin pain.

Primary outcome measures

• Change in MRI-derived total kidney volume between active pain and follow-up assessments in participants with episodic loin pain [Time frame: Within 72 hours of active loin pain onset and at follow-up assessment at least 2 weeks after the first visit.]
• Change in MRI-derived renal cortical volume between active pain and follow-up assessments in participants with episodic loin pain [Time frame: Within 72 hours of active loin pain onset and at follow-up assessment at least 2 weeks after the first visit.]
• Change in MRI-derived renal medullary volume between active pain and follow-up assessments in participants with episodic loin pain [Time frame: Within 72 hours of active loin pain onset and at follow-up assessment at least 2 weeks after the first visit.]
• Change in MRI-derived renal T1 relaxation time between active pain and follow-up assessments in participants with episodic loin pain [Time frame: Within 72 hours of active loin pain onset and at follow-up assessment at least 2 weeks after the first visit.]
• Presence of renal pelvis abnormality on renal MRI in participants with episodic loin pain and participants with no history of loin pain [Time frame: Within 72 hours of active loin pain onset and at follow-up assessment at least 2 weeks after the first visit.]
• Difference in MRI-derived total kidney volume between participants with episodic loin pain and participants with no history of loin pain [Time frame: Within 72 hours of pain onset for participants with episodic loin pain and baseline assessment after enrolment for participants with no history of loin pain.]
• Difference in MRI-derived renal cortical volume between participants with episodic loin pain and participants with no history of loin pain [Time frame: Within 72 hours of pain onset for participants with episodic loin pain and baseline assessment after enrolment for participants with no history of loin pain.]
• Difference in MRI-derived renal medullary volume between participants with episodic loin pain and participants with no history of loin pain [Time frame: Within 72 hours of pain onset for participants with episodic loin pain and baseline assessment after enrolment for participants with no history of loin pain.]
• Difference in MRI-derived renal T1 relaxation time between participants with episodic loin pain and participants with no history of loin pain [Time frame: Within 72 hours of pain onset for participants with episodic loin pain and baseline assessment after enrolment for participants with no history of loin pain.]
• Assessment of organ-level changes between pain-prone patients and those with no history of loin pain using structural renal magnetic resonance imaging (MRI) [Time frame: Within 72 hours of pain onset for participants with episodic loin pain and baseline assessment after enrolment for participants with no history of loin pain.]

Secondary outcome measures (8)

• Untargeted Liquid Chromatography-Tandem Mass spectrometry (LC-MS/MS) analysis to analyse differences in the urinary proteome between an active pain episode and when it subsides [Time frame: Within 72 hours of active loin pain onset and at follow-up assessment at least 2 weeks after the first visit]
• Untargeted Liquid Chromatography-Tandem Mass spectrometry (LC-MS/MS) analysis to analyse the differences in the urinary proteome between pain-prone patients and those with no history of loin pain [Time frame: Within 72 hours of pain onset for participants with episodic loin pain and baseline assessment after enrolment for participants with no history of loin pain.]
• Assessing the difference in molecules of interest between an active pain episode and when it subsides using enzyme-linked immunosorbent assay (ELISA) in urine, serum, and plasma [Time frame: Within 72 hours of active loin pain onset and at follow-up assessment at least 2 weeks after the first visit]
• Assessing the difference in molecules of interest between pain-prone patients and those who do not have a history of loin pain using enzyme-linked immunosorbent assay (ELISA) in urine, serum, and plasma. [Time frame: Within 72 hours of pain onset for participants with episodic loin pain and baseline assessment after enrolment for participants with no history of loin pain.]
• Comparing the presence of urinary factors that indicate active intra-renal injury between an active pain episode and when it subsides using urine microscopy [Time frame: Within 72 hours of active loin pain onset and at follow-up assessment at least 2 weeks after the first visit]
• Comparing the presence of urinary factors that indicate active intra-renal injury between an pain-prone patients and those with no history of loin pain using urine microscopy [Time frame: Within 72 hours of pain onset for participants with episodic loin pain and baseline assessment after enrolment for participants with no history of loin pain.]
• Comparing the presence of urinary factors that indicate active intra-renal injury between an active pain episode and when it subsides using the urine dipstick test [Time frame: Within 72 hours of active loin pain onset and at follow-up assessment at least 2 weeks after the first visit]
• Comparing the presence of urinary factors that indicate active intra-renal injury between an pain-prone patients and those with no history of loin pain using the urine dipstick test [Time frame: Within 72 hours of pain onset for participants with episodic loin pain and baseline assessment after enrolment for participants with no history of loin pain.]

Eligibility criteria

Inclusion criteria

Cohort A

• ≥18 years of age at the time of recruitment
• IgAN diagnosis confirmed with a renal biopsy
• Episodic/Intermittent Loin Pain (defined as pain at least once every 6 months)
• Have the capacity to consent to the study Cohort B

1\) ≥18 years of age at the time of recruitment 2) IgAN diagnosis confirmed with a renal biopsy 3) No history of loin pain 4) Have the capacity to consent to the study

Exclusion criteria

Cohort A

• Constant loin pain
• Infrequent loin pain (no pain experienced in the last 6 months)
• Inability to differentiate loin pain from back pain
• Other renal diseases
• Therapies that interfere with immune-mediation like steroids and complement inhibitors
• Kidney transplant recipients
• Current participation in an interventional study that may affect kidney function
• Patients on dialysis
• Patients with implants that are not MRI-safe (pacemakers, implantable defibrillators, cochlear implants, some shunts, neurostimulators, some aneurysm clips, etc.)

Cohort B

• Other renal diseases
• Therapies that interfere with immune-mediation like steroids and complement inhibitors
• Kidney transplant recipients
• Current participation in an interventional study that may affect kidney function
• Patients on dialysis
• Patients with conditions/implants that are not MRI-compatible (claustrophobia, pacemakers, implantable defibrillators, cochlear implants, some shunts, neurostimulators, some aneurysm clips, etc.)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

United Kingdom · 1 center

• University Hospitals of Leicester — Leicester

Identifiers

NCT: NCT07649538 · 1104 · 364280

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗