Kidney Transplantation in the Immunologically High-Risk Patient
Embargo until
2015-05-01
Date
2014-03-31
Authors
Orandi, Babak John
Journal Title
Journal ISSN
Volume Title
Publisher
Johns Hopkins University
Abstract
Survival for dialysis patients is dismal. They have an adjusted mortality rate 6.5-7.9 times higher than the general population. Kidney transplant (KT) recipients enjoy significant survival and quality of life advantages compared to remaining dialysis-dependent (1-5). Unfortunately, kidney demand far exceeds supply, with over 90,000 on the wait list (5). Highly sensitized patients constitute an increasingly large part of the wait list (6).
Advancements in desensitization have allowed for KT across previously insurmountable immunological barriers; however, incompatible live donor kidney transplantation (ILDKT) is in its nascency and the literature is limited by single-center data, small sample sizes, and publication bias. ILDKT risks are generally considered to be higher than for compatible KT, but these risks have never been quantified precisely. Chapter 2 does precisely this using primary data collected from 22 U.S. transplant centers, constituting the largest cohort of ILDKT patients in existence.
ILDKT risks are not limited to recipients. The federal government provides strict oversight of transplant outcomes. Chapter 2 quantifies the regulatory risk centers assume when they transplant immunologically high-risk patients.
IKT patients are also at elevated risk of antibody-mediated rejection (AMR), which mediates much of the graft loss in ILDKT. Chapter 3 details the formation of the world's largest cohort of AMR patients, defined using strict clinical, pathological, and immunologic criteria, and quantification of the risk of graft loss associated with AMR by transplant type.
There exists an uncommon, but virulent phenotype of AMR in ILDKT patients that is rapid in onset, severe in the graft dysfunction it causes, difficult to treat, and immediately graft-threatening without prompt action. Chapter 4 describes these patients in detail and compares the early rescue rate and impact of the severe AMR episode on the development of transplant glomerulopathy between salvage modalities, offering novel insight into the management of this challenging and devastating ILDKT complication.
Overall, this dissertation explores the risk of ILDKT to patients and centers, and delves into particular aspects of AMR within the context of ILDKT.
Description
Keywords
HLA-incompatible kidney transplantation, antibody-mediated rejection