Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation

Jennifer D. Motter; Kyle R. Jackson; Jane J. Long; Madeleine M. Waldram; Babak J. Orandi; Robert A. Montgomery; Mark D. Stegall; Stanley C. Jordan; Enrico Benedetti; Ty B. Dunn; Lloyd E. Ratner; Sandip Kapur; Ronald P. Pelletier; John P. Roberts; Marc L. Melcher; Pooja Singh; Debra L. Sudan; Marc P. Posner; Jose M. El-Amm; Ron Shapiro; Matthew Cooper; Jennifer E. Verbesey; George S. Lipkowitz; Michael A. Rees; Christopher L. Marsh; Bashir R. Sankari; David A. Gerber; Jason R. Wellen; Adel Bozorgzadeh; A. Osama Gaber; Eliot C. Heher; Francis L. Weng; Arjang Djamali; J. Harold Helderman; Beatrice P. Concepcion; Kenneth L. Brayman; Jose Oberholzer; Tomasz Kozlowski; Karina Covarrubias; Allan B. Massie; Dorry L. Segev; Jacqueline M. Garonzik-Wang

doi:10.1111/ajt.16471

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation

Jennifer D. Motter, Kyle R. Jackson, Jane J. Long, Madeleine M. Waldram, Babak J. Orandi, Robert A. Montgomery, Mark D. Stegall, Stanley C. Jordan, Enrico Benedetti, Ty B. Dunn, Lloyd E. Ratner, Sandip Kapur, Ronald P. Pelletier, John P. Roberts, Marc L. Melcher, Pooja Singh, Debra L. Sudan, Marc P. Posner, Jose M. El-Amm, Ron ShapiroMatthew Cooper, Jennifer E. Verbesey, George S. Lipkowitz, Michael A. Rees, Christopher L. Marsh, Bashir R. Sankari, David A. Gerber, Jason R. Wellen, Adel Bozorgzadeh, A. Osama Gaber, Eliot C. Heher, Francis L. Weng, Arjang Djamali, J. Harold Helderman, Beatrice P. Concepcion, Kenneth L. Brayman, Jose Oberholzer, Tomasz Kozlowski, Karina Covarrubias, Allan B. Massie, Dorry L. Segev, Jacqueline M. Garonzik-Wang

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

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Abstract

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = _1.031.68_2.72). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction >.1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = _1.452.09_3.02; PFNC = _1.672.40_3.46; PCC = _1.482.24_3.37). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction =.1), its impact on DCGF risk was less consequential for ILDKT (aHR = _1.341.62_1.95) than CLDKT (aHR = _1.962.29_2.67) (p interaction =.004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Original language	English
Pages (from-to)	1612-1621
Number of pages	10
Journal	American Journal of Transplantation
Volume	21
Issue number	4
DOIs	https://doi.org/10.1111/ajt.16471
State	Published - Apr 2021

Keywords

clinical research/practice
delayed graft function (DGF)
desensitization
graft survival
histocompatibility
kidney transplantation/nephrology
patient survival
rejection: acute

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10.1111/ajt.16471

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Motter, J. D., Jackson, K. R., Long, J. J., Waldram, M. M., Orandi, B. J., Montgomery, R. A., Stegall, M. D., Jordan, S. C., Benedetti, E., Dunn, T. B., Ratner, L. E., Kapur, S., Pelletier, R. P., Roberts, J. P., Melcher, M. L., Singh, P., Sudan, D. L., Posner, M. P., El-Amm, J. M., ... Garonzik-Wang, J. M. (2021). Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation. American Journal of Transplantation, 21(4), 1612-1621. https://doi.org/10.1111/ajt.16471

@article{5eaed01f928147b89e912d735bd42497,

title = "Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation",

abstract = "Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.031.682.72). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction >.1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.452.093.02; PFNC = 1.672.403.46; PCC = 1.482.243.37). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction =.1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.341.621.95) than CLDKT (aHR = 1.962.292.67) (p interaction =.004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.",

keywords = "clinical research/practice, delayed graft function (DGF), desensitization, graft survival, histocompatibility, kidney transplantation/nephrology, patient survival, rejection: acute",

author = "Motter, {Jennifer D.} and Jackson, {Kyle R.} and Long, {Jane J.} and Waldram, {Madeleine M.} and Orandi, {Babak J.} and Montgomery, {Robert A.} and Stegall, {Mark D.} and Jordan, {Stanley C.} and Enrico Benedetti and Dunn, {Ty B.} and Ratner, {Lloyd E.} and Sandip Kapur and Pelletier, {Ronald P.} and Roberts, {John P.} and Melcher, {Marc L.} and Pooja Singh and Sudan, {Debra L.} and Posner, {Marc P.} and El-Amm, {Jose M.} and Ron Shapiro and Matthew Cooper and Verbesey, {Jennifer E.} and Lipkowitz, {George S.} and Rees, {Michael A.} and Marsh, {Christopher L.} and Sankari, {Bashir R.} and Gerber, {David A.} and Wellen, {Jason R.} and Adel Bozorgzadeh and Gaber, {A. Osama} and Heher, {Eliot C.} and Weng, {Francis L.} and Arjang Djamali and Helderman, {J. Harold} and Concepcion, {Beatrice P.} and Brayman, {Kenneth L.} and Jose Oberholzer and Tomasz Kozlowski and Karina Covarrubias and Massie, {Allan B.} and Segev, {Dorry L.} and Garonzik-Wang, {Jacqueline M.}",

note = "Publisher Copyright: {\textcopyright} 2020 The American Society of Transplantation and the American Society of Transplant Surgeons",

year = "2021",

month = apr,

doi = "10.1111/ajt.16471",

language = "English",

volume = "21",

pages = "1612--1621",

journal = "American Journal of Transplantation",

issn = "1600-6135",

number = "4",

}

Motter, JD, Jackson, KR, Long, JJ, Waldram, MM, Orandi, BJ, Montgomery, RA, Stegall, MD, Jordan, SC, Benedetti, E, Dunn, TB, Ratner, LE, Kapur, S, Pelletier, RP, Roberts, JP, Melcher, ML, Singh, P, Sudan, DL, Posner, MP, El-Amm, JM, Shapiro, R, Cooper, M, Verbesey, JE, Lipkowitz, GS, Rees, MA, Marsh, CL, Sankari, BR, Gerber, DA, Wellen, JR, Bozorgzadeh, A, Gaber, AO, Heher, EC, Weng, FL, Djamali, A, Helderman, JH, Concepcion, BP, Brayman, KL, Oberholzer, J, Kozlowski, T, Covarrubias, K, Massie, AB, Segev, DL & Garonzik-Wang, JM 2021, 'Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation', American Journal of Transplantation, vol. 21, no. 4, pp. 1612-1621. https://doi.org/10.1111/ajt.16471

TY - JOUR

T1 - Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation

AU - Motter, Jennifer D.

AU - Jackson, Kyle R.

AU - Long, Jane J.

AU - Waldram, Madeleine M.

AU - Orandi, Babak J.

AU - Montgomery, Robert A.

AU - Stegall, Mark D.

AU - Jordan, Stanley C.

AU - Benedetti, Enrico

AU - Dunn, Ty B.

AU - Ratner, Lloyd E.

AU - Kapur, Sandip

AU - Pelletier, Ronald P.

AU - Roberts, John P.

AU - Melcher, Marc L.

AU - Singh, Pooja

AU - Sudan, Debra L.

AU - Posner, Marc P.

AU - El-Amm, Jose M.

AU - Shapiro, Ron

AU - Cooper, Matthew

AU - Verbesey, Jennifer E.

AU - Lipkowitz, George S.

AU - Rees, Michael A.

AU - Marsh, Christopher L.

AU - Sankari, Bashir R.

AU - Gerber, David A.

AU - Wellen, Jason R.

AU - Bozorgzadeh, Adel

AU - Gaber, A. Osama

AU - Heher, Eliot C.

AU - Weng, Francis L.

AU - Djamali, Arjang

AU - Helderman, J. Harold

AU - Concepcion, Beatrice P.

AU - Brayman, Kenneth L.

AU - Oberholzer, Jose

AU - Kozlowski, Tomasz

AU - Covarrubias, Karina

AU - Massie, Allan B.

AU - Segev, Dorry L.

AU - Garonzik-Wang, Jacqueline M.

PY - 2021/4

Y1 - 2021/4

N2 - Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.031.682.72). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction >.1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.452.093.02; PFNC = 1.672.403.46; PCC = 1.482.243.37). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction =.1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.341.621.95) than CLDKT (aHR = 1.962.292.67) (p interaction =.004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

AB - Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.031.682.72). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction >.1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.452.093.02; PFNC = 1.672.403.46; PCC = 1.482.243.37). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction =.1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.341.621.95) than CLDKT (aHR = 1.962.292.67) (p interaction =.004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

KW - clinical research/practice

KW - delayed graft function (DGF)

KW - desensitization

KW - graft survival

KW - histocompatibility

KW - kidney transplantation/nephrology

KW - patient survival

KW - rejection: acute

UR - http://www.scopus.com/inward/record.url?scp=85101966820&partnerID=8YFLogxK

U2 - 10.1111/ajt.16471

DO - 10.1111/ajt.16471

M3 - Article

C2 - 33370502

AN - SCOPUS:85101966820

SN - 1600-6135

VL - 21

SP - 1612

EP - 1621

JO - American Journal of Transplantation

JF - American Journal of Transplantation

IS - 4

ER -

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation

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