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

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

Study Overview

• Status: Unknown
• 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

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.

• Study Type: Observational
• Enrollment (Anticipated): 180

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
    • Contact: Jiang Gengru; Phone Number: +86-13917983703; Email: jianggeng-ru@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients from Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, RenJi Hospital, Shanghai Zhongshan Hospital, Longhua Hospital Shanghai University of Traditional Chinese Medicine and Shanghai East Hospital

Description

Inclusion Criteria:

1. IgA nephropathy:

1. Age: 18-80 years.
2. Patients diagnosed with primary IgA nephropathy by renal biopsy.
3. Estimated glomerular filtration rate (using the 2009 CKD-EPI formula) ≥30ml/min/1.73/m^2.
4. 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:

1. Annual eGFR loss rate <3ml/min/1.73m^2.
2. eGFR>90ml/min/1.73m^2. 2) Non-progressive IgAN patients:

Meet at least one of the following:

1. eGFR decrease of more than 50% from baseline (in the absence of other possible causes of kidney damage).
2. Annual eGFR loss rate >5ml/min/1.73m^2.
3. 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:

1. Kidney biopsy shows crescentic IgAN or MCD-IgAN.;
2. Patients with secondary IgAN;
3. During pregnancy or lactation;
4. After kidney transplantation;
5. More than one serious acute infection in the psat 12 months;
6. Chronic infection;
7. Use of glucocorticosteroids and other immunosuppressive drugs within the last 6 months;
8. Incomplete medical history or clinical data.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
IgAN patients at low risk of disease progression; n = 30, incipient disease	Drug: Intervention for incipient patients at low risk of disease progression; Conservative treatment, if necessary use ACEI/ARB and titrated to the maximum tolerated dose, with a BP-lowering goal of < 130/80 mm Hg
IgAN patients at high risk of disease progression; n = 60, incipient disease	Drug: Intervention for patients at high risk of disease progression; 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.
Long-term stable patients; n = 30, follow-up for at least 15 years
Progressive IgAN patients; n = 30
Healthy control; 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	Time Frame
24-hour urine protein level	24 weeks
Serum albumin level	24 weeks
eGFR (estimated using the 2009 CKD-EPI formula)	24 weeks

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Collaborators: Shanghai Zhongshan Hospital; RenJi Hospital; Shanghai University of Traditional Chinese Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2020
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: June 17, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 19, 2020

Study Record Updates

• Last Update Posted (Actual): August 28, 2020
• Last Update Submitted That Met QC Criteria: August 26, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Biomarker; IgA Nephropathy; IR-Seq
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: XHEC-C-2020-070-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No