The Effect of Monthly Anti-CD25+ Treatment with Basiliximab on the Progression of Chronic Renal Dysfunction after Lung Transplantation

Abstract

Background: Chronic renal dysfunction (CRD), as predominantly related to calcineurin-inhibitor (CNI) nephrotoxicity, is associated with increased morbidity and mortality after lung transplantation (LTx). Basiliximab (BSX), a recombinant chimeric monoclonal antibody against CD25⁺ on activated T-lymphocytes, although often employed as an “induction immunosuppression” after solid organ transplantation, may further allow for reduction in CNI exposure with monthly administration and amelioration of CRD.

Objective: To determine the effect of monthly anti-CD25⁺ treatment with basiliximab on the progression of chronic renal dysfunction after lung transplantation.

Methods: Post-LTx recipients with stages IIIB-V CRD were treated with monthly intravenous infusion of BSX 20 mg. They were analyzed for creatinine clearance at 1, 3, 6, and 12 months; rate of the change in the clearance (the slope of the regression line) and FEV₁/month; de novo HLA class I or II DSA; and infectious events (IE). Tacrolimus (TAC) trough levels were concurrently targeted at 2–4 ng/mL during BSX therapy. The criteria for BSX discontinuation included acute lung allograft rejection, acute respiratory infection, and progression to end-stage renal disease (ESRD).

Results: 9 LTx recipients were treated with BSX for ≥6 months. The median time past after their LTx was 1853 (range: 75–7212) days; the mean±SD age was 64.3±11.3 years; the male:female ratio was 7:2. The baseline mean±SD creatinine clearance 1–3 months prior to BSX initiation was 22.8±5.14 mL/min/1.73 m² (CI: 3.95) consistent with CRD stages—IIIB (2), IV (6), and V (1). Prior to BSX treatment, all 9 patients had established CLAD—obstructive-phenotype (BOS, n=4) and restrictive-phenotype (RAS, n=5). During the course of BSX treatment, the aggregate creatinine clearance mean slope increased by a mean±SD of 0.747±0.467 mL/min/1.72 m²/month (CI: 0.359), consistent with “stabilization” of renal function in 7 patients; deterioration occurred in 2 with transition to chronic hemodialysis. Spirometric stability in lung allograft function was observed in 5 patients with a mean±SD aggregate FEV₁ slope of ‑1.49±1.08 mL/month (CI: 2.50). 3 deaths occurred due to the following conditions during BSX treatment—HFpEF/ Sepsis + CLAD/Parainfluenza type 2 bronchiolitis + CLAD. 2 recipients developed “weak MFI” HLA class II DSA; no HLA class I DSA was detected during the treatment.

Conclusion: Renal sparing therapy with monthly BSX infusion with concurrent reduction in CNI exposure (TAC = 2–4 ng/mL) for stages IIIB-V CRD was associated with stability in creatinine clearance in 78% of patients over a treatment course of 6–12 months. Pre-existing CLAD afflicting all patients and inherent variability in progression of chronic rejection, limits our assessment of BSX efficacy in this context. We detected an infrequent de novo HLA class II DSA during BSX therapy.