Serum TGF-β1 and MCP-1 levels predict good prognosis in IgA nephropathy patients on immunosuppressive therapy

IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally and a leading cause of end-stage kidney disease. Despite its prevalence, disease-specific therapeutic options are limited, and responses to immunosuppressive therapy are highly inconsistent. This variability underscores a critical need for reliable prognostic biomarkers to identify patients most likely to respond favorably to treatment, enabling more personalized and effective management strategies and preventing progression to kidney failure.

This prospective cohort study enrolled 202 adults with biopsy-proven IgAN between 2010 and 2020. Good prognosis was defined as a ≥50% reduction in urine protein-to-creatinine ratio (uPCR) or <0.5 g/g with preserved estimated glomerular filtration rate one year post-biopsy. Researchers analyzed serum and urine levels of cytokines/chemokines including TGF-β1, MCP-1, RANTES, and VEGF, alongside intrarenal immune cell infiltration (e.g., CD45+, CD3+, CD20+, and Ki-67+ cells) to identify prognostic markers.

Among the 202 patients, 120 (59.4%) achieved a good prognosis, demonstrating a significantly lower risk of end-stage kidney disease over a 10-year follow-up. Multivariable analyses identified several independent predictors of good prognosis: immunosuppressive therapy, low histologic grade, lower uPCR, absence of hypertension, higher serum TGF-β1 levels, and reduced intrarenal CD45+ and CD3+ cell infiltration. Specifically, among patients receiving immunosuppressive therapy:

Higher serum TGF-β1 (adjusted odds ratio [aOR], 1.16; 95% CI, 1.04-1.31) and lower serum MCP-1 (aOR, 0.99; 95% CI, 0.97-1.00) independently predicted good prognosis. Conversely, for patients receiving only supportive care, less intrarenal CD20+ cell infiltration (aOR, 0.22; 95% CI, 0.07-0.73) independently predicted a good prognosis, highlighting distinct prognostic signatures based on treatment approach.