O35
PREVENTING THE DEVELOPMENT OF DONOR SPECIFIC ANTIBODIES IN
KIDNEY TRANSPLANT RECIPIENTS THROUGH OPTIMAL
IMMUNOSUPPRESSION – A RETROSPECTIVE ANALYSIS OF A SINGLE
CENTRE TRANSPLANT UNIT
Hughes, S1,2, Worthington, J 1, Strickland-Hodge, B 2, DeFrietas, D 1
¹CMFT, Manchester, ²School of Healthcare, Leeds University
INTRODUCTION:
Life-long potent immunosuppression is prescribed following transplantation to prevent host
detection of the allograft with ensuing rejection and subsequent failure of the organ. Detection
of newly formed (de novo) donor specific antibodies (DSA) in the serum of transplant
recipients indicates host immunity directed towards the allograft and has been shown to be
responsible for late allograft failure. De novo DSA have been associated with underimmunosuppression, particularly in non-adherent patients. This study aimed to demonstrate
that sub-optimal immunosuppression post-transplant was associated with the development of
de novo DSA.
METHODS:
This retrospective case-control study compared immunosuppression regimes in de novo DSA
positive patients, in a regional transplant centre (n=45), with DSA negative recipients with
similar allograft dysfunction. All patients were tested for DSA due to unexplained graft
dysfunction, defined as proteinurea or raised serum creatinine. The total immunosuppression
prescribed in the 12 months prior to testing was measured as well as documented by clinician
of patient non-adherence. Baseline factors between the two groups, including time from
transplant, age, induction therapy, acute rejection and HLA mismatch, showed no significant
difference. Sub-therapeutic dosing was defined as consecutive tacrolimus levels less than
4.5ng/ml, consecutive ciclosporin less than 50ng/ml, mycophenolate less than 50% of
recommended dose or azathioprine less than 1mg/kg/day. All prednisolone doses were
recorded for each patient.
RESULTS:
Patients with de novo DSA were shown to be exposed to a significantly lower
immunosuppression burden in the 12 months prior to testing (p=0.0022). This was most
notable with CNI treatment, where sub-therapeutic serum CNI levels were associated with de
novo DSA detection (p=0.0011; RR 2.27 95% CI 1.3-3.97). A trend towards lower
mycophenolate use was seen in DSA positive group but this was not significant. Steroids did
not appear to affect de novo DSA development in this study. De novo DSA development
severely affected allograft survival, with 14/49 and 1/48 graft failures in the DSA positive and
negative group respectively. The median allograft survival post-DSA testing was of 36
months. The addition or increasing of immunosuppression post-DSA detection by clinicians
was shown to have no effect on allograft survival however a larger study is required to
confirm this.
CONCLUSION:
This single centre analysis demonstrates that sub-optimal immunosuppression is associated
with the detection of de novo DSA in a kidney transplant population. Low levels of CNI
through sub-optimal dosing or non-adherence was associated with the development of de
novo DSA in this single centre study. Mycophenolate failed to show a significant association
with de novo DSA development, probably due to the low use in the population study and due
to the difficulty detecting non-adherence of mycophenolate (mycophenolate therapeutic drug
monitoring is not performed at the local centre). Drug minimisation and patient nonadherence of maintenance immunosuppression should be reviewed in each transplant
recipient to prevent de novo DSA development and subsequent allograft dysfunction.