APOL1 genotype and kidney transplantation outcomes from deceased african American donors

Barry I. Freedman; Stephen O. Pastan; Ajay K. Israni; David Schladt; Bruce A. Julian; Michael D. Gautreaux; Vera Hauptfeld; Robert A. Bray; Howard M. Gebel; Allan D. Kirk; Robert S. Gaston; Jeffrey Rogers; Alan C. Farney; Giuseppe Orlando; Robert J. Stratta; Sumit Mohan; Lijun Ma; Carl D. Langefeld; Donald W. Bowden; Pamela J. Hicks; Nicholette D. Palmer; Amudha Palanisamy; Amber M. Reeves-Daniel; W. Mark Brown; Jasmin Divers

doi:10.1097/TP.0000000000000969

APOL1 genotype and kidney transplantation outcomes from deceased african American donors

Barry I. Freedman^*, Stephen O. Pastan, Ajay K. Israni, David Schladt, Bruce A. Julian, Michael D. Gautreaux, Vera Hauptfeld, Robert A. Bray, Howard M. Gebel, Allan D. Kirk, Robert S. Gaston, Jeffrey Rogers, Alan C. Farney, Giuseppe Orlando, Robert J. Stratta, Sumit Mohan, Lijun Ma, Carl D. Langefeld, Donald W. Bowden, Pamela J. HicksNicholette D. Palmer, Amudha Palanisamy, Amber M. Reeves-Daniel, W. Mark Brown, Jasmin Divers

^*Corresponding author for this work

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

143 Scopus citations

Abstract

Background. Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors. Methods. The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLAmatch, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed. Results. Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 - 10^-4), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant. Conclusions. Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.

Original language	English
Pages (from-to)	194-202
Number of pages	9
Journal	Transplantation
Volume	100
Issue number	1
DOIs	https://doi.org/10.1097/TP.0000000000000969
State	Published - 2016
Externally published	Yes

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Freedman, B. I., Pastan, S. O., Israni, A. K., Schladt, D., Julian, B. A., Gautreaux, M. D., Hauptfeld, V., Bray, R. A., Gebel, H. M., Kirk, A. D., Gaston, R. S., Rogers, J., Farney, A. C., Orlando, G., Stratta, R. J., Mohan, S., Ma, L., Langefeld, C. D., Bowden, D. W., ... Divers, J. (2016). APOL1 genotype and kidney transplantation outcomes from deceased african American donors. Transplantation, 100(1), 194-202. https://doi.org/10.1097/TP.0000000000000969

@article{0e8d9359fb624de6ae0e028c2794f78d,

title = "APOL1 genotype and kidney transplantation outcomes from deceased african American donors",

abstract = "Background. Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors. Methods. The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLAmatch, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed. Results. Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 - 10-4), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant. Conclusions. Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.",

author = "Freedman, {Barry I.} and Pastan, {Stephen O.} and Israni, {Ajay K.} and David Schladt and Julian, {Bruce A.} and Gautreaux, {Michael D.} and Vera Hauptfeld and Bray, {Robert A.} and Gebel, {Howard M.} and Kirk, {Allan D.} and Gaston, {Robert S.} and Jeffrey Rogers and Farney, {Alan C.} and Giuseppe Orlando and Stratta, {Robert J.} and Sumit Mohan and Lijun Ma and Langefeld, {Carl D.} and Bowden, {Donald W.} and Hicks, {Pamela J.} and Palmer, {Nicholette D.} and Amudha Palanisamy and Reeves-Daniel, {Amber M.} and {Mark Brown}, W. and Jasmin Divers",

year = "2016",

doi = "10.1097/TP.0000000000000969",

language = "English",

volume = "100",

pages = "194--202",

journal = "Transplantation",

issn = "0041-1337",

publisher = "LWW",

number = "1",

}

Freedman, BI, Pastan, SO, Israni, AK, Schladt, D, Julian, BA, Gautreaux, MD, Hauptfeld, V, Bray, RA, Gebel, HM, Kirk, AD, Gaston, RS, Rogers, J, Farney, AC, Orlando, G, Stratta, RJ, Mohan, S, Ma, L, Langefeld, CD, Bowden, DW, Hicks, PJ, Palmer, ND, Palanisamy, A, Reeves-Daniel, AM, Mark Brown, W & Divers, J 2016, 'APOL1 genotype and kidney transplantation outcomes from deceased african American donors', Transplantation, vol. 100, no. 1, pp. 194-202. https://doi.org/10.1097/TP.0000000000000969

TY - JOUR

T1 - APOL1 genotype and kidney transplantation outcomes from deceased african American donors

AU - Freedman, Barry I.

AU - Pastan, Stephen O.

AU - Israni, Ajay K.

AU - Schladt, David

AU - Julian, Bruce A.

AU - Gautreaux, Michael D.

AU - Hauptfeld, Vera

AU - Bray, Robert A.

AU - Gebel, Howard M.

AU - Kirk, Allan D.

AU - Gaston, Robert S.

AU - Rogers, Jeffrey

AU - Farney, Alan C.

AU - Orlando, Giuseppe

AU - Stratta, Robert J.

AU - Mohan, Sumit

AU - Ma, Lijun

AU - Langefeld, Carl D.

AU - Bowden, Donald W.

AU - Hicks, Pamela J.

AU - Palmer, Nicholette D.

AU - Palanisamy, Amudha

AU - Reeves-Daniel, Amber M.

AU - Mark Brown, W.

AU - Divers, Jasmin

PY - 2016

Y1 - 2016

N2 - Background. Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors. Methods. The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLAmatch, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed. Results. Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 - 10-4), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant. Conclusions. Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.

AB - Background. Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors. Methods. The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLAmatch, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed. Results. Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 - 10-4), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant. Conclusions. Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.

UR - http://www.scopus.com/inward/record.url?scp=84952630141&partnerID=8YFLogxK

U2 - 10.1097/TP.0000000000000969

DO - 10.1097/TP.0000000000000969

M3 - Article

C2 - 26566060

AN - SCOPUS:84952630141

SN - 0041-1337

VL - 100

SP - 194

EP - 202

JO - Transplantation

JF - Transplantation

IS - 1

ER -

APOL1 genotype and kidney transplantation outcomes from deceased african American donors

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