Biomarkers predicting good prognosis among patients receiving immunosuppressive treatment in IgA nephropathy: the promising role of serum TGF-β1 and MCP-1

Background IgA nephropathy (IgAN) exhibits a highly variable clinical course. As responses to immunosuppressive therapy remain inconsistent, reliable prognostic markers are critically required to identify patients who can show a good response to immunosuppressive treatments. Methods This prospective cohort study enrolled adults with biopsy-proven IgAN from 2010-2020. Good prognosis was defined as a ≥50% reduction in the urine protein-to-creatinine ratio (uPCR) or <0.5 g/g with preserved estimated glomerular filtration rate 1 year after biopsy. Serum and urine cytokines/chemokines (TGF-β1, MCP-1, RANTES, and VEGF) and intrarenal CD45 + , CD3 + , CD20 + , and Ki-67 + cells were analyzed. Results Among the 202 patients, 120 (59.4%) had a good prognosis and showed a significantly lower risk of end-stage kidney disease over a 10-year follow-up. Multivariable analyses identified immunosuppressive therapy, low histologic grade, lower uPCR, absence of hypertension, higher serum TGF-β1 levels, and reduced intrarenal CD45 + and CD3 + cell infiltration as independent predictors of good prognosis. Among patients receiving immunosuppressive therapy, higher serum TGF-β1 (adjusted odds ratio [aOR], 1.16; 95% confidence interval [CI], 1.04–1.31) and lower serum MCP-1 (aOR, 0.99; 95% CI, 0.97–1.00) independently predicted good prognosis, whereas less intrarenal CD20 + cell infiltration (aOR, 0.22; 95% CI, 0.07–0.73) independently predicted good prognosis in patients receiving supportive care only. Conclusions Serum TGF-β1 and MCP-1 levels may serve as biomarkers of favorable prognosis among patients with IgAN receiving immunosuppressive therapy, whereas intrarenal CD20 + cell infiltration may reflect poor prognosis under supportive care. Integrating serum cytokine profiles and tissue immune signatures may help inform individualized treatment decisions for IgAN.