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Presenter: Olga, Charnaya, Washington, United States
Authors: Olga Charnaya, Asha Moudgil
Effect of donor specific anti-HLA antibodies on graft function in single-center pediatric cohort
Olga Charnaya1, Asha Moudgil1.
1Nephrology, Children's National Health System, Washington, DC, United States
Introduction: The development of de novo donor specific antibodies (dnDSA) has been shown to decrease long-term graft survival of kidney transplants in both adult and pediatric patients[1][2][3]. Routine screening for dnDSA can offer a window of opportunity for treatment prior to onset of irreversible graft damage. In our center, we screen for dnDSA at 6 months, annually and at times of graft dysfunction. Upon detection, patients undergo biopsy and treatment with IVIG and steroids as initial therapy followed by rituximab (C1q binding dnDSA) and plasma exchange (C4d+ antibody mediated AR). We compared graft survival among patients that did and did not develop dnDSA.
Materials and Methods: Of 72 kidney transplant recipients at Children's National Medical Center from January 2008 until June 2015, 67 (primary transplants with <20% PRA at transplant and a negative flow cross match) were included in this retrospective analysis. Glomerular filtration rate (GFR) was estimated by the old Schwartz or MDRD equations at the time of the first clinic visit and annually thereafter.
Results and Discussion: De novo DSA developed in 32.8% of patients after 628+/- 466 days. Demographic and clinical characteristics are shown in the table. There was no difference in these variables amongst those with and without dnDSA except for increased number of preemptive transplants amongst dnDSA + cohort. Kaplan-Meier (Figure 2) analysis of graft survival found no difference between the two groups at 6 years of follow-up.
Conclusion: Development of dnDSA had no effect on graft survival in our cohort. This may be due to an early intervention with targeted therapy. Planned further investigation includes an expanded evaluation for risk factors including development of viral load, DR MM and, non-adherence as measured by calculating the coefficient of variation of tacrolimus levels. Finally, we plan to evaluate if early and aggressive treatment of dnDSA makes a difference in outcome by comparing it to an adult cohort with dnDSA but managed conservatively at the University of Maryland.
[1] Ginevri F, Nocera A, Comoli P et al. Posttransplant de novo donor-specific hla antibodies identify pediatric kidney recipients at risk for late antibody-mediated rejection. Am J Transplant . 2012 Dec;12(12):3355-62
[2] Eid L, Tuchman S, Moudgil A. Late acute rejection: incidence, risk factors, and effect on graft survival and function. Pediatr Transplant. 2014 Mar; 18(2): 155-62
[3] Chaudhuri A, Ozawa M, Everly MJ. The clinical impact of humoral immunity in pediatric renal transplantation. JASN. 2013 Mar;24(4):655-64