The goal of this open-label, randomized study is to evaluate the efficacy and safety of the personalized treatment model in which Gd-IgA1 is dynamically monitored to guide medication adjustment in progressive IgAN patients treated with Nefecon or telitacicept. Researchers will compare two groups of participants: those who have Gd-IgA1 checked regularly during treatment, and those who do not. This is to find out if regular Gd-IgA1 checks can help doctors adjust medication better and get better treatment results.
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a leading cause of end-stage renal disease (ESRD) in young adults. Even with standard supportive care, many patients still experience worsening renal function and eventually develop ESRD. The widely accepted multi-hit pathogenesis of IgAN recognizes the production of galactose-deficient IgA1 (Gd-IgA1) as the key step. Pathogenic Gd-IgA1 forms immune complexes that deposit in the kidney, triggering inflammation and renal damage, which serves as a target for new regimens. Two novel targeted therapies have shown positive clinical effects for IgAN: 1. Budesonide Enteric Capsules (Nefecon): A gut-targeted oral preparation that releases drugs in the ileocecal region, reducing Gd-IgA1 production and renal immune deposition to protect renal function. 2. Telitacicept: A dual Blys/APRIL inhibitor that blocks the proliferation of B cells to reduce pathogenic Gd-IgA1 production. However, the clinical effects of these novel therapies usually take time to appear (e.g., a significant drop in urinary protein with Nefecon is often seen 3 to 6 months after treatment). Early, sensitive indicators reflecting therapeutic effects are needed to enable timely adjustment of treatment plans. Biomarkers (e.g., Gd-IgA1) decline earlier than urinary protein, which is highly significant for monitoring early treatment efficacy and optimizing personalized treatment decisions.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
374
Participants in the experimental group will undergo a total of five Gd-IgA1 tests at baseline and during the follow-up period, and their clinicians will use these results to guide medication adjustment.
Peking University First Hospital
Beijing, Beijing Municipality, China
RECRUITINGMean change in 24-hour proteinuria from baseline at the end of follow-up
Time frame: From enrollment to the end of follow-up at 12 months
Mean change in 24-hour proteinuria from baseline at the midpoint of follow-up
Time frame: From enrollment to the middle of follow-up period at 6 months
Change in estimated glomerular filtration rate (eGFR)
eGFR is calculated using the CKD-EPI method.
Time frame: From enrollment to the end of follow-up at 12 months
Complete remission of proteinuria
24-hour urine total protein ≤ 0.3 g with a concurrent eGFR decline ≤ 30%
Time frame: From enrollment to the midpoint of follow-up (6 months) and over the entire 12-month follow-up period
Immunosuppressant exposure measures
Cumulative dosage of non-corticosteroid immunosuppressants, cumulative dosage of systemic corticosteroids converted to prednisone-equivalent dosage, and number of corticosteroid bolus therapy courses during follow-up. Consecutive daily bolus doses count as one course; topical corticosteroids are excluded.
Time frame: From enrollment to the end of follow-up at 12 months
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