The Applicaiton of Immune Repertoire in the Diagnosis and Disease Monitoring of IgA Nephropathy

Study Overview
=================
Brief Summary
-----------------
This prospective study aims to investigate the role of IR-Seq in the diagnosis and disease monitoring in patients with IgA nephropathy.

Detailed Description
-----------------
Autoimmunity may play an important role in IgA nephropathy, and previous studies have shown that immune repertoire sequencing (IR-Seq) may help elucidate the dynamic changes of immune repertoire (IR) in autoimmune disease states. To further explore the potential application value of this technology, we will conduct a series of prospective studies to investigate the role of IR-Seq in the diagnosis and disease monitoring in patients with IgA nephropathy.

Official Title
-----------------
The Applicaiton of Immune Repertoire in the Diagnosis and Disease Monitoring of IgA Nephropathy

Conditions
-----------------
IgA Nephropathy

Intervention / Treatment
-----------------
* Drug: Intervention for incipient patients at low risk of disease progression
* Drug: Intervention for patients at high risk of disease progression


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. IgA nephropathy: Age: 18-80 years. Patients diagnosed with primary IgA nephropathy by renal biopsy. Estimated glomerular filtration rate (using the 2009 CKD-EPI formula) ≥30ml/min/1.73/m^2. Obtain informed consent from patients. 2. Healthy Control: Gender, age and ethnicity matched health volunteers. 3. IgAN patients were further divided into 4 groups, as defined below: 1) Long-term stable patients: Follow-up for at least 15 years and meet at least one of the following: Annual eGFR loss rate <3ml/min/1.73m^2. eGFR>90ml/min/1.73m^2. 2) Non-progressive IgAN patients: Meet at least one of the following: eGFR decrease of more than 50% from baseline (in the absence of other possible causes of kidney damage). Annual eGFR loss rate >5ml/min/1.73m^2. Progress to ESRD. 3) IgAN patients at low risk of disease progression: Proteinuria ≤ 1g/24h after 3 months of optimized supportive care. 4) IgAN patients at high risk of disease progression: Proteinuria > 1g/24h despite 3 months of optimized supportive care. Exclusion Criteria: Kidney biopsy shows crescentic IgAN or MCD-IgAN.; Patients with secondary IgAN; During pregnancy or lactation; After kidney transplantation; More than one serious acute infection in the psat 12 months; Chronic infection; Use of glucocorticosteroids and other immunosuppressive drugs within the last 6 months; Incomplete medical history or clinical data.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IgAN patients at low risk of disease progression<br>n = 30, incipient disease | Drug: Intervention for incipient patients at low risk of disease progression<br>* Conservative treatment, if necessary use ACEI/ARB and titrated to the maximum tolerated dose, with a BP-lowering goal of < 130/80 mm Hg<br>|
| IgAN patients at high risk of disease progression<br>n = 60, incipient disease | Drug: Intervention for patients at high risk of disease progression<br>* BP-lowering goal of < 125/75 mm Hg and treat with steroids or steroids combined with immunosuppressants based on optimal supportive therapy: If GFR>60 ml/min/1.73m^2, oral prednisone 0.6-0.8 mg/kg/day ( (maximum dose 48 mg/day) for 2 months, followed by a monthly dose reduction of 8 mg for 24 weeks. If GFR is 30-60 ml/min/1.73m^2, intravenous cyclophosphamide (CTX) 750 mg per month per m^2 for 6 months, along with oral prednisone (at the same dose as 1); if intravenous administration is unacceptable, then the above regimen was replaced with oral mycophenolate mofetil 500 mg bid for 24 weeks.<br>|
| Long-term stable patients<br>n = 30, follow-up for at least 15 years | |
| Progressive IgAN patients<br>n = 30 | |
| Healthy control<br>n = 30 | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary protein remission rate | Including complete and partial remission rate of urinary protein. Complete remission criteria: post-treatment urine protein <0.3 g/24h; partial remission criteria: post-treatment urine protein <50% of the maximum value. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour urine protein level |  | 24 weeks | 
| Serum albumin level |  | 24 weeks | 
| eGFR (estimated using the 2009 CKD-EPI formula) |  | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IgA Nephropathy, IR-Seq, Biomarker