Persistent versus resolved donor-specific antibodies predict 10-year antibody-mediated rejection and kidney transplant outcomes in Thailand

Abstract

Preformed donor-specific HLA antibodies (DSA) are a major risk factor for antibody-mediated rejection (ABMR) and graft loss after kidney transplantation. While pre-transplant desensitization can reduce DSA levels, the impact of persistent vs. resolved DSA on long-term outcomes remains unclear. This study investigated the association between post-transplant DSA status and clinical outcomes in kidney transplant recipients. This retrospective cohort study investigated the impact of post-transplant DSA persistence on clinical outcomes in kidney transplant recipients at King Chulalongkorn Memorial Hospital between 2009 and 2019. Patients with pre-transplant DSA positivity (detected by Luminex but negative by CDC-AHG) were categorized into 'resolved' (DSA < 500 MFI) and 'persistent' (DSA > 500 MFI) groups based on post-transplant Luminex results. Outcomes evaluated included biopsy-proven acute rejection (ABMR and TCMR), graft loss, mortality, and post-transplant complications. A total of 50 KTr were enrolled in the study. The median (interquartile range, IQR) DSA level was 1,556 (3,491) MFI for class I and 0 (888) MFI for class II. 57% of patients underwent pre-transplant desensitization. The median follow-up time after transplantation was 5.5 (IQR 3.3) years. The group with persistent DSA (n = 16) exhibited a significant higher rate of ABMR compared to the group with resolved DSA (n = 34) (p = 0.047, log-rank test). Factors associated with persistent DSA included recipient age over 50 and lower tacrolimus levels at six months (less than 7.25 ng/mL). Monitoring DSA levels is crucial in kidney transplant recipients, as persistent DSA is strongly associated with an increased risk of ABMR. Maintaining higher tacrolimus levels at 6 months tends to resolve DSA post-transplant. For patients with persistent DSA, surveillance biopsies should be considered to facilitate early detection and treatment of rejection, thus preserving kidney allograft function.

Keywords: Kidney transplantation; Kinetic; Persistent; Preformed Donor-Specific HLA antibodies; Resolved.

Fig. 1

Survivor functions of biopsy-proven antibody-mediated rejection (ABMR) in post-kidney transplant recipients with persistent and resolved DSA, adjusted by time to DSA follow-up.

Fig. 2

Serum creatinine levels (A), estimated glomerular filtration rate (eGFR) calculated using the CKD-EPI 2009 equation (B), tacrolimus trough levels (C), and 24-h urine protein levels (D) in post-kidney transplant recipients with persistent and resolved DSA.