APOL1 Genotyping of African American Deceased Organ Donors: Not Just Yet

Knoll, Greg

doi:10.1111/ajt.13230

Cited by 17 publications

(16 citation statements)

References 5 publications

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“…No study has examined the potential interaction of APOL1 genotype of the donors, deceased or living, and recipients, or fully accounted for other factors that likely reduce survival rates, including rejection, bacterial or viral infections, recurrent disease, and donor-specific anti-HLA antibodies. We agree with other investigators that adequately powered prospective studies are urgently needed to better define the potential effects of APOL1 genotypes in kidney transplantation 37, 38 …”

Section: Discussionsupporting

confidence: 81%

Apolipoprotein L1 Gene Effects on Kidney Transplantation

Freedman

Locke

Reeves‐Daniel

et al. 2017

Seminars in Nephrology

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The pathogenesis of many common etiologies of nephropathy has been informed by recent molecular genetics breakthroughs. It is now apparent that the ethnic disparity in risk for non-diabetic chronic kidney disease between African Americans and European Americans is largely explained by variation in the apolipoprotein L1 gene (APOL1). Presence of two APOL1 renal-risk variants markedly increases an individual’s risk for kidney disease. In transplantation, kidneys from deceased African Americans with two APOL1 renal-risk variants have shorter survival intervals after engraftment, regardless of the ethnicity of the recipient. Precision medicine will transform the clinical practice of nephrology and kidney transplantation, and play an important role in the allocation of kidneys from deceased and living kidney donors with recent African ancestry. This article reviews existing data on APOL1 in deceased- and living-donor kidney transplantation. It considers the impact of including APOL1 genotyping in decisions on the allocation and discard of deceased-donor kidneys, as well as the selection of living donors.

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Section: Discussionsupporting

confidence: 81%

Apolipoprotein L1 Gene Effects on Kidney Transplantation

Freedman

Locke

Reeves‐Daniel

et al. 2017

Seminars in Nephrology

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“…We suggest that approaches to rapidly perform APOL1 genotyping in deceased AA kidney donors be developed and a national trial performed to prospectively test their impact on transplantation outcomes. (8,29)…”

Section: Discussionmentioning

confidence: 99%

APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors

et al. 2016

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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 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, HLA match, 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-two-renal-risk-variant kidneys (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-two-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than in recipients of zero/one 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 non-significant. Conclusions Shorter renal allograft survival is reproducibly observed after DDKT from APOL1-two-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.

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“…However, in a recent editorial, Chandraker [26] surmised that there are insufficient data to recommend testing all AA potential donors with the aim of excluding individuals with both APOL1 risk variants. Similarly, Ojo and Knoll [27] concluded that APOL1 genotypes should not be currently used to guide the allocation or consent processes for kidneys from deceased organ donors. Although screening AA living kidney donors for APOL1 gene variant is currently not routinely performed, such screening and excluding those with 2 APOL 1 risk alleles may have the potential to further increase existing disparities between AA individuals and European Americans, since AAs might be more likely to have the APOL1 gene variant and thus more likely to be excluded as a potential donor.…”

Section: Disparities In Posttransplant Outcomes Among Aasmentioning

confidence: 99%

Health Disparities in Kidney Transplantation for African Americans

Harding¹,

Mersha

Pham

et al. 2017

Am J Nephrol

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Background: The persistent challenges of bridging healthcare disparities for African Americans (AAs) in need of kidney transplantation continue to be unresolved at the national level. This healthcare disparity is multifactorial: stemming from limited kidney donors suitable for AAs; inconsistent care coordination and suboptimal risk factor control; social determinants, low socioeconomic status, reduced access to care; and mistrust of clinicians and the healthcare system. Summary: There are numerous opportunities to significantly lessen the disparities in kidney transplantation for AAs through the following measures: the adoption of new care and patient engagement models that include education, enhanced practice-level cultural sensitivity, and timely referral as well as increased research on the impact of the environment on genetic risk, and implementation of new transplantation-related policies. Key Messages: This systematic review describes pretransplant concerns related to access to kidney transplantation, posttransplant complications, and policy interventions to address the challenging issues associated with kidney transplantation in AAs.

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APOL1 Genotyping of African American Deceased Organ Donors: Not Just Yet

Cited by 17 publications

References 5 publications

Apolipoprotein L1 Gene Effects on Kidney Transplantation

Apolipoprotein L1 Gene Effects on Kidney Transplantation

APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors

Health Disparities in Kidney Transplantation for African Americans

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