Approximately 2000-4000 patients per year in need of a kidney transplant are predicted to find a healthy, willing live donor with whom they are ABO or HLA incompatible. Some might find compatible exchanges through kidney paired donation;however, evidence suggests that 50% of incompatible pairs will not benefit from paired donation due to broad HLA sensitization or hard-to-match blood types. For these patients, incompatible living donor kidney transplantation (ILDKT) is the only other option besides joining the 90,000-patient deceased donor (DD) waiting list, where waiting times average 5-7 years and death rates average 5-10% per year. ILDKT is an emerging practice in which patients can receive kidney transplants across antibody barriers using a variety of desensitization techniques, which generally utilize plasmapheresis and intravenous immunoglobulin, which are not without significant risk and side effects. Unfortunately, characterization of the outcomes of these patients is limited, as the UNOS national transplant registry does not collect data on incompatibilities, and inherent publication bias limits the current paradigm. Single-center reports suggest that risk of graft loss following ILDKT is higher than that following compatible living donor transplants. This has never been studied on a national level, and only at this level will there be power to make robust inferences about the role of ILDKT-specific factors in predicting graft survival. By obtaining data from every U.S. transplant center on their ILDKT patients and linking them in a novel way to the UNOS registry, we seek to quantify the independent role of antibody strength, class, and source in predicting graft-related outcomes after ILDKT, as well as to quantify the characteristics associated with patient survival after ILDKT desensitization protocols. This exploratory research will establish a framework for patient selection and counseling for ILDKT that is evidence-based and in the best interest of patients. Robust quantification of the risk and survival benefit associated with ILDKT and its desensitization protocols is novel and will be immediately useable clinically throughout the country. A better understanding of this emerging modality at a national, generalizable level will help improve the feasibility, availability, and quality of ILDKT for the thousands of patients each year who could potentially benefit from it.

Public Health Relevance

Although live donor kidney transplantation is the best treatment for kidney failure, many patients who have a healthy, willing donor cannot undergo the operation because they are incompatible with their donor. Incompatible kidney transplantation is a relatively new practice that allows patients to receive transplants despite their incompatibility;however knowledge of these patients'outcomes is limited because they have not been studied on a national level. This project's goal is to link information specific to the incompatible transplants with an already existing transplant outcomes registry on a national level, creating a much bigger study population from which to make meaningful conclusions about patient selection, counseling, and quality assurance for this specialized procedure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK093218-03
Application #
8596815
Study Section
Special Emphasis Panel (ZDK1-GRB-G (M1))
Program Officer
Rankin, Tracy L
Project Start
2012-01-07
Project End
2015-01-06
Budget Start
2014-01-07
Budget End
2015-01-06
Support Year
3
Fiscal Year
2014
Total Cost
$73,734
Indirect Cost
Name
Johns Hopkins University
Department
Surgery
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Orandi, B J; Garonzik-Wang, J M; Massie, A B et al. (2014) Quantifying the risk of incompatible kidney transplantation: a multicenter study. Am J Transplant 14:1573-80
Orandi, Babak J; Zachary, Andrea A; Dagher, Nabil N et al. (2014) Eculizumab and splenectomy as salvage therapy for severe antibody-mediated rejection after HLA-incompatible kidney transplantation. Transplantation 98:857-63