Lymphocytic expression and IL-2 levels in calcineurin inhibitor-resistant nephrotic syndrome due to focal segmental glomerulosclerosis: Implications for calcineurin inhibitor response

Abstract

Background and objective Calcineurin inhibitors (CNI) are the first-line treatment for steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS), though response rates vary. This study analyzed lymphocyte activation through IL-2 receptor expression on T lymphocytes and serum IL-2Rα (soluble CD25) levels in these patients to evaluate their relationship with response to CNI therapy.

Materials and methods A multicenter case-control study was conducted with 39 patients with steroid-resistant FSGS, diagnosed via renal biopsy, and 23 healthy controls. Clinical, biochemical, and immunological variables were assessed. Soluble CD25 levels were measured using ELISA, and lymphocyte activation was analyzed by flow cytometry. Treatment criteria and response evaluation followed KDIGO guidelines. Diagnostic performance was assessed using ROC curves for soluble CD25.

Results 48.7% of patients responded to CNI treatment. Soluble CD25 levels and IL-2 expression on CD3 T lymphocytes were significantly associated with CNI response (p < 0.01): responders had higher CD25 levels (477 ± 84.47 pg/mL) compared to non-responders (290.28 ± 85.98 pg/mL). Responders showed a significant reduction in soluble CD25 (-35.8%) and CD3-IL2+ cells after remission, alongside increases in CD8 DR + cells and regulatory T cells. ROC analysis identified a soluble CD25 cutoff of 324 pg/mL, with 94% sensitivity and 75% specificity for predicting response to CNI.

Conclusions Elevated soluble CD25 levels and T cell activation were associated with better CNI response. Soluble CD25 could be a predictive biomarker to identify patients with higher likelihood of response, optimizing therapeutic decisions and avoiding unnecessary treatments in steroid-resistant FSGS.