Association of Recipient APOL1 Kidney Risk Alleles With Kidney Transplant Outcomes.
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
01 Dec 2023
01 Dec 2023
Historique:
medline:
28
11
2023
pubmed:
1
8
2023
entrez:
1
8
2023
Statut:
ppublish
Résumé
Kidney transplant survival in African American recipients is lower compared with non-African American transplant recipients. APOL1 risk alleles (RA) have been postulated as likely contributors. We examined the graft outcomes in kidney transplant recipients (KTRs) stratified by APOL1 RA status in a multicenter observational prospective study. The Renal Transplant Outcome Study recruited a cohort of incident KTRs at 3 transplant centers in the Philadelphia area from 1999-2004. KTRs were genotyped for APOL1 RA. Allograft and patient survival rates were compared by the presence and number of APOL1 RA. Among 221 participants, approximately 43% carried 2 APOL1 RA. Recipients carrying 2 APOL1 RA demonstrated lower graft survival compared with recipients with only 1 or none of APOL1 RA at 1 y posttransplant, independently of other donor and recipient characteristics (adjusted hazard ratio 3.2 [95% confidence interval, 1.0-10.4], P = 0.05). There was no significant difference in overall survival or graft survival after 3 y posttransplantation. There was no difference in death by APOL1 -risk status ( P = 0.11). Recipients with 2 APOL1 high-risk alleles exhibited lower graft survival 1 y posttransplantation compared with recipients with only 1 or 0 APOL1 RA. Further research is required to study the combined role of the recipient and donor APOL1 genotypes in kidney transplantation.
Sections du résumé
BACKGROUND
BACKGROUND
Kidney transplant survival in African American recipients is lower compared with non-African American transplant recipients. APOL1 risk alleles (RA) have been postulated as likely contributors. We examined the graft outcomes in kidney transplant recipients (KTRs) stratified by APOL1 RA status in a multicenter observational prospective study.
METHODS
METHODS
The Renal Transplant Outcome Study recruited a cohort of incident KTRs at 3 transplant centers in the Philadelphia area from 1999-2004. KTRs were genotyped for APOL1 RA. Allograft and patient survival rates were compared by the presence and number of APOL1 RA.
RESULTS
RESULTS
Among 221 participants, approximately 43% carried 2 APOL1 RA. Recipients carrying 2 APOL1 RA demonstrated lower graft survival compared with recipients with only 1 or none of APOL1 RA at 1 y posttransplant, independently of other donor and recipient characteristics (adjusted hazard ratio 3.2 [95% confidence interval, 1.0-10.4], P = 0.05). There was no significant difference in overall survival or graft survival after 3 y posttransplantation. There was no difference in death by APOL1 -risk status ( P = 0.11).
CONCLUSIONS
CONCLUSIONS
Recipients with 2 APOL1 high-risk alleles exhibited lower graft survival 1 y posttransplantation compared with recipients with only 1 or 0 APOL1 RA. Further research is required to study the combined role of the recipient and donor APOL1 genotypes in kidney transplantation.
Identifiants
pubmed: 37527489
doi: 10.1097/TP.0000000000004742
pii: 00007890-990000000-00497
doi:
Substances chimiques
Apolipoprotein L1
0
APOL1 protein, human
0
Types de publication
Multicenter Study
Observational Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2575-2580Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Références
Feyssa E, Jones-Burton C, Ellison G, et al. Racial/ethnic disparity in kidney transplantation outcomes: influence of donor and recipient characteristics. J Natl Med Assoc. 2009;101:111–115.
Bekbolsynov D, Mierzejewska B, Khuder S, et al. Improving access to HLA-matched kidney transplants for African American patients. Front Immunol. 2022;13:832488.
Isaacs RB, Nock SL, Spencer CE, et al. Racial disparities in renal transplant outcomes. Am J Kidney Dis. 1999;34:706–712.
Ojo AO, Wolfe RA, Held PJ, et al. Delayed graft function: risk factors and implications for renal allograft survival. Transplantation. 1997;63:968–974.
Swanson SJ, Hypolite IO, Agodoa LY, et al. Effect of donor factors on early graft survival in adult cadaveric renal transplantation. Am J Transplant. 2002;2:68–75.
Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010;329:841–845.
Limou S, Nelson GW, Kopp JB, et al. APOL1 kidney risk alleles: population genetics and disease associations. Adv Chronic Kidney Dis. 2014;21:426–433.
Kopp JB, Nelson GW, Sampath K, et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol. 2011;22:2129–2137.
Kramer HJ, Stilp AM, Laurie CC, et al. African ancestry-specific alleles and kidney disease risk in Hispanics/Latinos. J Am Soc Nephrol. 2017;28:915–922.
Lee BT, Kumar V, Williams TA, et al. The APOL1 genotype of African American kidney transplant recipients does not impact 5-year allograft survival. Am J Transplant. 2012;12:1924–1928.
Freedman BI, Julian BA, Pastan SO, et al. Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure. Am J Transplant. 2015;15:1615–1622.
Zhang Z, Sun Z, Fu J, et al. Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes. J Clin Invest. 2021;131:e146643.
Bayer ND, Cochetti PT, Anil Kumar MS, et al. Association of metabolic syndrome with development of new-onset diabetes after transplantation. Transplantation. 2010;90:861–866.
David VA, Binns-Roemer EA, Winkler CA. Taqman assay for genotyping CKD-associated APOL1 SNP rs60910145: a cautionary note. Kidney Int Rep. 2019;4:184–185.
Parsa A, Kao WH, Xie D, et al.; AASK Study Investigators. APOL1 risk variants, race, and progression of chronic kidney disease. N Engl J Med. 2013;369:2183–2196.
Foster MC, Coresh J, Fornage M, et al. APOL1 variants associate with increased risk of CKD among African Americans. J Am Soc Nephrol. 2013;24:1484–1491.
Peralta CA, Bibbins-Domingo K, Vittinghoff E, et al. APOL1 genotype and race differences in incident albuminuria and renal function decline. J Am Soc Nephrol. 2016;27:887–893.
Kopp JB, Winkler CA, Zhao X, et al.; FSGS-CT Study Consortium. Clinical features and histology of apolipoprotein L1-associated nephropathy in the FSGS clinical trial. J Am Soc Nephrol. 2015;26:1443–1448.
Lan X, Jhaveri A, Cheng K, et al. APOL1 risk variants enhance podocyte necrosis through compromising lysosomal membrane permeability. Am J Physiol Renal Physiol. 2014;307:F326–F336.
Olabisi OA, Zhang JY, VerPlank L, et al. APOL1 kidney disease risk variants cause cytotoxicity by depleting cellular potassium and inducing stress-activated protein kinases. Proc Natl Acad Sci U S A. 2016;113:830–837.
Chen DP, Zaky ZS, Schold JD, et al. Podocyte density is reduced in kidney allografts with high-risk APOL1 genotypes at transplantation. Clin Transplant. 2021;35:e14234.
Egbuna O, Zimmerman B, Manos G, et al.; VX19-147-101 Study Group. Inaxaplin for proteinuric kidney disease in persons with two APOL1 variants. N Engl J Med. 2023;388:969–979.
Reeves-Daniel AM, DePalma JA, Bleyer AJ, et al. The APOL1 gene and allograft survival after kidney transplantation. Am J Transplant. 2011;11:1025–1030.