Yi-Shen-Hua-Shi granule added to supportive care reduces proteinuria in IgA nephropathy: a multicenter randomized controlled trial.

IgA nephropathy is the most common primary glomerulonephritis globally. Current management relies on supportive care, but many patients remain at risk for progressive disease, especially those with persistent proteinuria. This study evaluated the efficacy of Yi-Shen-Hua-Shi granule in adult patients with IgA nephropathy and persistent proteinuria. We conducted a multicenter, randomized, controlled trial involving adults with biopsy-confirmed IgA nephropathy, estimated glomerular filtration rate ≥30 mL/min/1.73 m2, and persistent proteinuria despite optimized supportive therapy. Participants were randomized 1:1 to receive Yi-Shen-Hua-Shi granule (10 g, orally, twice daily) plus best supportive care, or best supportive care alone, for 8 weeks. The primary endpoint was change in 24-hour urinary protein from baseline to week 8. Secondary endpoints included changes in renal function and safety assessments. Data were analyzed using linear mixed-effects models according to the intention-to-treat principle. A total of 97 patients were included. At 8 weeks, the Yi-Shen-Hua-Shi group showed a significantly greater reduction in 24-hour proteinuria compared with controls, with an estimated mean difference of ≈340 mg (95% CI 89.59 to 588.62; p = 0.01). The benefit was most pronounced among participants with baseline proteinuria >1000 mg, whose reduction was approximately 505 mg greater than controls (95% CI 152.45 to 859.42; p = 0.01). No significant differences in estimated glomerular filtration rate or adverse event rates were observed between groups. Yi-Shen-Hua-Shi granule, added to best supportive care, safely produced a greater short-term reduction in proteinuria, particularly in patients with high baseline proteinuria.