Donor Specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients

INTRODUCTION

The development of de novo donor-specific antibodies (dnDSA) has been associated with rejection and graft loss in kidney transplantation, and DSA screening is now recommended in all kidney transplant recipients. However, the clinical significance of dnDSA in patients with a stable creatinine remains unclear.

METHODS

We performed a retrospective cohort study of 103 patients receiving a first, kidney alone transplant between 12/1/2007 and 12/31/2013. Inclusion criteria were age <18 years old at the time of transplant and at least two years of DSA monitoring. All patients underwent DSA screening every 3 months post-transplant with additional testing as clinically indicated. No treatment was given for DSAs in the absence of biopsy-proven rejection.

RESULTS

20 patients (19%) developed dnDSA in the setting of a stable creatinine and 13 patients (13%) developed dnDSA in the setting of an elevated creatinine. Median follow-up time post-transplant was 4.1 (IQR 2.9-5.7) years. In a Cox proportional hazards regression controlling for age, type of transplant, delayed graft function, cold ischemia time, and baseline eGFR post-transplant, developing dnDSA with a stable creatinine was not associated with time to 30% decline in eGFR (HR 0.88, 95%CI 0.30-2.00 p=0.598) or graft loss. dnDSA with an elevated creatinine was associated with a 2.8 times increased risk of decline in graft function (95% CI 1.08-7.27 p=0.034) and a 7.34 times increased risk of graft loss (95%CI 1.37-39.23 p=0.020) compared to transplant recipients who did not develop dnDSA. The presence of dnDSA with a stable creatinine was associated with an increased risk of rejection within 3 years (RR 2.53 95%CI 1.49-4.3 p=0.0002) and moderate interstitial fibrosis and tubular atrophy at 2 years post-transplant (aOR 26.8 95%cI 1.91-138 p=0.015).

CONCLUSION

The clinical setting in which dnDSA is first detected impacts the association between dnDSA and graft function. dnDSA with a stable creatinine is associated with future rejection episodes and IFTA, but does not correlate with time to 30% decline in eGFR. dnDSA with an elevated creatinine is associated with a 30% decline in graft function, graft loss, and rejection. Further research is needed to clarify the role of dnDSA screening in pediatric kidney transplantation.