Multiple abnormal peripheral blood gene expression assay results are correlated with subsequent graft loss after kidney transplantation

Raymond Lackner Heilman; James N. Fleming; Martin Mai; Byron Smith; Walter D. Park; John Holman; Mark D. Stegall

doi:10.1111/ctr.14987

Multiple abnormal peripheral blood gene expression assay results are correlated with subsequent graft loss after kidney transplantation

Raymond Lackner Heilman, James N. Fleming, Martin Mai, Byron Smith, Walter D. Park, John Holman, Mark D. Stegall

Research output: Contribution to journal › Article › peer-review

Abstract

Background: The aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post-transplant year with outcomes after kidney transplantation. Methods: We conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post-transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx-all GEP results normal, 1 Not-TX had one GEP result abnormal and >1 Not-TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation. Results: We enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not-TX n = 59 (25%) and >1 Not-TX n = 64 (27%). Compared to the TX group, the >1 Not-TX group had lower eGFR (p <.001) and more chronic changes on 1-year surveillance biopsy (p =.007). Death censored graft survival showed inferior graft survival in the >1 Not-TX group (p <.001) but not in the 1 Not-TX group. All graft losses in the >1 Not-TX group occurred after 1-year post-transplant. Conclusions: We conclude that a pattern of persistently Not-TX GEP assay correlates with inferior graft survival.

Original language	English (US)
Journal	Clinical Transplantation
DOIs	https://doi.org/10.1111/ctr.14987
State	Accepted/In press - 2023

Keywords

graft survival
kidney transplant outcomes
peripheral blood gene expression

ASJC Scopus subject areas

Transplantation

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10.1111/ctr.14987

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@article{3e5984e040bb47bbb26d6000393df962,

title = "Multiple abnormal peripheral blood gene expression assay results are correlated with subsequent graft loss after kidney transplantation",

abstract = "Background: The aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post-transplant year with outcomes after kidney transplantation. Methods: We conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post-transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx-all GEP results normal, 1 Not-TX had one GEP result abnormal and >1 Not-TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation. Results: We enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not-TX n = 59 (25%) and >1 Not-TX n = 64 (27%). Compared to the TX group, the >1 Not-TX group had lower eGFR (p <.001) and more chronic changes on 1-year surveillance biopsy (p =.007). Death censored graft survival showed inferior graft survival in the >1 Not-TX group (p <.001) but not in the 1 Not-TX group. All graft losses in the >1 Not-TX group occurred after 1-year post-transplant. Conclusions: We conclude that a pattern of persistently Not-TX GEP assay correlates with inferior graft survival.",

keywords = "graft survival, kidney transplant outcomes, peripheral blood gene expression",

author = "Heilman, {Raymond Lackner} and Fleming, {James N.} and Martin Mai and Byron Smith and Park, {Walter D.} and John Holman and Stegall, {Mark D.}",

note = "Funding Information: This was a prospective observation study performed at the three Mayo Clinic transplant centers which are in Minnesota, Florida, and Arizona. Patients were recruited between 2016 and 2018. The study was funded by grants from the Mayo Clinic Center for Individualized Medicine and Transplant Genomics. The Mayo Clinic Institutional Review Board approved the study. All patients provided written informed consent. The clinical and research activities being reported are consistent with the Principles of the Declaration of Istanbul as outlined in the “Declaration of Istanbul on Organ Trafficking and Transplant Tourism.” Publisher Copyright: {\textcopyright} 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",

year = "2023",

doi = "10.1111/ctr.14987",

language = "English (US)",

journal = "Clinical Transplantation",

issn = "0902-0063",

publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Multiple abnormal peripheral blood gene expression assay results are correlated with subsequent graft loss after kidney transplantation

AU - Heilman, Raymond Lackner

AU - Fleming, James N.

AU - Mai, Martin

AU - Smith, Byron

AU - Park, Walter D.

AU - Holman, John

AU - Stegall, Mark D.

N1 - Funding Information: This was a prospective observation study performed at the three Mayo Clinic transplant centers which are in Minnesota, Florida, and Arizona. Patients were recruited between 2016 and 2018. The study was funded by grants from the Mayo Clinic Center for Individualized Medicine and Transplant Genomics. The Mayo Clinic Institutional Review Board approved the study. All patients provided written informed consent. The clinical and research activities being reported are consistent with the Principles of the Declaration of Istanbul as outlined in the “Declaration of Istanbul on Organ Trafficking and Transplant Tourism.” Publisher Copyright: © 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2023

Y1 - 2023

N2 - Background: The aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post-transplant year with outcomes after kidney transplantation. Methods: We conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post-transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx-all GEP results normal, 1 Not-TX had one GEP result abnormal and >1 Not-TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation. Results: We enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not-TX n = 59 (25%) and >1 Not-TX n = 64 (27%). Compared to the TX group, the >1 Not-TX group had lower eGFR (p <.001) and more chronic changes on 1-year surveillance biopsy (p =.007). Death censored graft survival showed inferior graft survival in the >1 Not-TX group (p <.001) but not in the 1 Not-TX group. All graft losses in the >1 Not-TX group occurred after 1-year post-transplant. Conclusions: We conclude that a pattern of persistently Not-TX GEP assay correlates with inferior graft survival.

AB - Background: The aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post-transplant year with outcomes after kidney transplantation. Methods: We conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post-transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx-all GEP results normal, 1 Not-TX had one GEP result abnormal and >1 Not-TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation. Results: We enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not-TX n = 59 (25%) and >1 Not-TX n = 64 (27%). Compared to the TX group, the >1 Not-TX group had lower eGFR (p <.001) and more chronic changes on 1-year surveillance biopsy (p =.007). Death censored graft survival showed inferior graft survival in the >1 Not-TX group (p <.001) but not in the 1 Not-TX group. All graft losses in the >1 Not-TX group occurred after 1-year post-transplant. Conclusions: We conclude that a pattern of persistently Not-TX GEP assay correlates with inferior graft survival.

KW - graft survival

KW - kidney transplant outcomes

KW - peripheral blood gene expression

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DO - 10.1111/ctr.14987

M3 - Article

C2 - 37026820

AN - SCOPUS:85152262044

SN - 0902-0063

JO - Clinical Transplantation

JF - Clinical Transplantation

ER -

Multiple abnormal peripheral blood gene expression assay results are correlated with subsequent graft loss after kidney transplantation

Abstract

Keywords

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