Apolipoprotein L1 Gene Effects on Kidney Transplantation

Freedman, Barry I.; Locke, Jayme E.; Reeves‐Daniel, Amber; Julian, Bruce A.

doi:10.1016/j.semnephrol.2017.07.006

Cited by 24 publications

(21 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In case of living donors, although very safe with modern surgical techniques, there is increasing evidence that living donors, especially certain racial and ethnic groups are at risk for developing chronic kidney disease few decades after donation. [15][16][17][18] If xenotransplantation is feasible and successful, it will eliminate living donation for sure.…”

Section: Advantages Of Xenotransplantationmentioning

confidence: 99%

Xenotransplantation

Tandukar

Hariharan

2018

Organogenesis

View full text Add to dashboard Cite

The transplantation of living cells, tissues or organs from one species to another is termed xenotransplantation. The history of xenotransplantation is as old as allogeneic transplantation itself. Early attempts were made at a time when the immunologic basis of organ rejection were poorly understood. The advent of potent immunosuppressive medications along with the parallel advances in the field of genetic engineering has provided a fresh perspective on the role of xenotransplantation as a means to alleviate the disparity between the number of candidates on the waitlist and the available organs. As the science behind xenotransplantation advances, the transplantation community must take it upon themselves to educate the community at large regarding both the benefits and potential risks of this promising field.

show abstract

Section: Advantages Of Xenotransplantationmentioning

confidence: 99%

Xenotransplantation

Tandukar

Hariharan

2018

Organogenesis

View full text Add to dashboard Cite

show abstract

“…Kidneys transplanted from African American deceased donors fail more rapidly than those from European American deceased donors (2). As a result, African American deceased-donor kidneys are generally perceived to be at higher risk for shortened allograft survival.…”

mentioning

confidence: 99%

Apolipoprotein L1 Gene Testing Comes of Age

Freedman

Larsen

2020

Kidney360

Self Cite

View full text Add to dashboard Cite

The landscape in nephrology changed dramatically in 2010 with the discovery of genetic association between two coding renal-risk variants (RRVs) in the apo L1 gene (APOL1) and CKD (1). The APOL1 G1 and G2 nephropathy-associated variants arose ,10,000 years ago and are present almost exclusively in individuals with recent African ancestry, those with similar genetic makeup to populations currently residing in Africa. The frequencies of these variants rapidly increased, likely due to positive selection for protection afforded from Trypanosoma brucei rhodesiense infection, a parasite causing African sleeping sickness. Due to the transAtlantic slave trade, approximately 39% of African Americans possess one APOL1 RRV and 13% possess two. In contrast, hemoglobin S (HbS) gene variants are also common in African Americans; however, ,8% inherit one or two HbS variants. Ancestry-based variation in APOL1 contributes to the excess risk of ESKD in African Americans, more rapid failure of transplanted kidneys from African American deceased donors, and higher rates of nephropathy in African American living-kidney donors (2,3). The kidney disease historically attributed to hypertension in nondiabetic African Americans with low-level proteinuria also proved to be APOL1 associated, with biopsy findings including solidified glomerulosclerosis and thyroidization-type tubular atrophy (4). In addition, the APOL1 spectrum of kidney disease includes FSGS, HIV-associated nephropathy (HIVAN), severe lupus nephritis, and sickle cell nephropathy (5). APOL1 RRVs are associated with nephropathy in individuals with recent African ancestry residing in the United States, Africa, Europe, South America, and the Caribbean. Beyond genetic association, APOL1 RRVs were shown to directly cause kidney disease in a transgenic mouse model (6). Recent studies show that APOL1 kidney risk variants do not associate with cardiovascular disease (7,8). Despite the evidence that APOL1 risk variants lead to kidney disease, the precise pathogenic mechanisms are not known. Data suggest a toxic gain of function conferred by RRVs and there is evidence to support that early mitochondrial injury may initiate cell death and scarring (9,10). These findings are changing clinical practice and informing basic research. This Kidney360 Perspective reviews potential indications for APOL1 genotyping (Table 1). The field is rapidly evolving and developments will likely necessitate more frequent testing in

show abstract

“…However, a critical shortage of kidneys exists, and deceased donor allograft survival declines over time. Retrospective studies detected more rapid failure of kidneys transplanted from deceased donors with APOL1 high-risk genotypes (2). This could explain why kidneys donated by blacks, on average, fail more rapidly after transplantation than kidneys from white donors (3).…”

mentioning

confidence: 99%

“…Because black donor kidneys, on average, fail more quickly after transplantation than kidneys from donors of other races, the KDRI assumes that all kidneys recovered from blacks have an equal risk for early graft failure. The KDRI was instituted before studies revealed that donor APOL1 genotypes might contribute to racial disparities in DDKT outcomes (2). Donor APOL1 genotype effects on allograft survival in DDKT from black donors seem comparable with (or stronger than) established risk factors for allograft failure, such as HLA match, cold ischemia time, and sensitization on the basis of panel reactive antibodies.…”

mentioning

confidence: 99%

“…The APOLLO will assess whether computing the KDRI with APOL1 genotype instead of the race variable can better predict longer kidney transplantation survival and lessen discard of good-quality kidneys (4). Despite strong retrospective data, implementation of APOL1 nephropathy risk variant screening in deceased kidney donors requires data from a well powered national prospective study (2,9). The APOLLO is a major step toward a more comprehensive approach to kidney transplantation.…”

mentioning

confidence: 99%

See 1 more Smart Citation