Genetics of acute rejection after kidney transplantation.
Casey R DorrWilliam S OettingPamala A JacobsonAjay K IsraniPublished in: Transplant international : official journal of the European Society for Organ Transplantation (2017)
Treatment of acute rejection (AR) following kidney transplantation has improved in recent years, but there are still limitations to successful outcomes. This review article covers literature in regard to recipient and donor genetics of AR kidney and secondarily of liver allografts. Many candidate gene and some genome-wide association studies (GWASs) have been conducted for AR in kidney transplantation. Genetic associations with AR in kidney and liver are mostly weak, and in most cases, the associations have not been reproducible. A limitation in the study of AR is the lack of sufficiently large populations that account for population stratification to study the AR phenotype which in this era occurs in <10% of transplants. Furthermore, the AR phenotype has been difficult to define and the definitions of classifications have evolved over time. Literature related to the pharmacogenomics of tacrolimus is robust and has been validated in many studies. Associations between gene expression and AR are emerging as markers of outcomes and AR classification. In the future, combinations of pretransplant genotype for AR risk prediction, genotype-based immune suppressant dosing, and pharmacogenomic markers to select AR maintenance or treatment and expression markers from biopsies may provide valuable clinical tools for guiding treatment.
Keyphrases
- kidney transplantation
- gene expression
- systematic review
- machine learning
- liver failure
- dna methylation
- metabolic syndrome
- adipose tissue
- emergency department
- poor prognosis
- deep learning
- insulin resistance
- drug induced
- combination therapy
- genome wide association
- current status
- clinical decision support
- aortic dissection
- mechanical ventilation
- case control