Treatment Effects of Chinese Medicine (Yi-Qi-Qing-Jie Herbal Compound) Combined With Immunosuppression Therapies in IgA Nephropathy Patients With High-risk of ESRD

The investigators plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until 50% (30/60) have a composite endpoint or have been followed for 3 years (study completion). All patients will receive optimal supportive care.

Inclusion criteria

• patients who maintain regular follow-ups at Guang'anmen Hospital, agree to participate, and provide informed consent;
• biopsy-proven IgA nephropathy, with recent progression to high-risk IgAN*;
• eGFR 15 to 60 ml/min/1.73 m2, calculated with the use of CKD-EPI Creatinine Equation 2009.

• High-risk IgAN: persistent proteinuria ≥ 1 g/d despite at least 8 weeks of optimal supportive care [maximally tolerated RAS blocker which refers to no symptomatic hypotension, no hyperkalemia, and serum creatinine increased by not more than 30% of baseline, blood pressure control meeting targets (135/85 mmHg or lower), and dietary management (sodium intake less than 6 g/d, protein intake of 0.6-0.8 g/kg/day, and low-fat diet)], the mean annual eGFR decline rate (eGFR-slope) >10 ml/min per 1.73 m2 per year, while needing to restart immunosuppressive therapy; or eGFR<60 ml/min/1.73 m2 at the first diagnosis.

Exclusion criteria

• secondary IgAN;
• comorbidity of other primary or secondary glomerular diseases;
• comorbidity of severe primary diseases such as cardiovascular, hepatic, cerebral, and hematopoietic system diseases or mental disorders;
• allergy or intolerance to the experimental medication (e.g., RAS blockers, prednisolone, cyclophosphamide, YQF compound and its placebo compound);
• contraindications to immunosuppression therapy-acute and chronic infectious diseases, malignancies, leukopenia, thrombocytopenia, gastrointestinal hemorrhage, ulcers of stomach or duodenum, post-transplantation;
• pregnant or lactating women;
• unwilling to participate in this study, failure to accept or tolerate Chinese medicine compound;
• history of alcohol or drug abuse;
• poor compliance, loss to follow-up;
• participation in another clinical investigation.