Testing for High-Risk Alleles in Potential Kidney Donors
Testing for High-Risk Alleles in Potential Kidney Donors
A separate issue is related to the effect of APOL1 alleles on transplant outcomes. Recipients of kidneys from African American donors have a higher risk of transplant failure. This was suggested by a cohort study with 79,361 patients who underwent kidney transplantation between 1991 and 2000. African American donor race was associated with increased risk of transplant failure in the recipient (relative risk, 1.28; 95% CI, 1.24–1.32), suggesting that these donated kidneys may have intrinsic predisposing factors for developing kidney disease. Part of this risk may be attributed to high-risk APOL1 alleles. Reeves-Daniel et al investigated the relationship between donor APOL1 risk variants and transplant survival after deceased donor kidney transplantation. The study included 136 kidneys from African American donors and their respective recipients, ~50% of whom were also African American. After accounting for global donor African ancestry, recipient age and sex, cold ischemia time, panel-reactive antibody, number of HLA antigen mismatches, and expanded criteria donation, the authors found that kidneys from African American deceased donors carrying 2 APOL1 risk alleles failed more rapidly posttransplantation than kidneys from deceased donors with 0 or 1 risk variant (hazard ratio, 3.84; P = 0.008). Differences in transplant survival based on APOL1 genotype distributions were evident 20 months posttransplantation. Of lost transplants with 2 APOL1 risk variants, 75% had biopsy-proven APOL1-associated lesions, including FSGS and/or arteriosclerosis, compared with 11.8% of lost transplants with 0 or 1 APOL1 risk allele.
In contrast to donor genotype, the presence of 2 APOL1 risk alleles in the recipient does not appear to be associated with decreased transplant survival. Lee et al investigated the impact of recipient APOL1 genotypes on transplant survival in 119 African American recipients. Approximately 38% of respective donors were African American. At 5 years posttransplantation, the rate of transplant loss was 22.4% in recipients carrying 2 APOL1 risk alleles compared to 21.3% in those with either 0 or 1 risk allele. In sum, these preliminary data suggest that APOL1 expression in the kidney is more relevant to kidney outcomes than systemic expression. Differences in transplant outcomes between kidneys from living and deceased donors with high-risk APOL1 alleles remain to be determined, especially with the potential role of ischemic injury in precipitating the initial kidney injury and differences in immunosuppressive regimens, including target trough levels of calcineurin inhibitors.
High-risk APOL1 Alleles and Recipient Outcomes
A separate issue is related to the effect of APOL1 alleles on transplant outcomes. Recipients of kidneys from African American donors have a higher risk of transplant failure. This was suggested by a cohort study with 79,361 patients who underwent kidney transplantation between 1991 and 2000. African American donor race was associated with increased risk of transplant failure in the recipient (relative risk, 1.28; 95% CI, 1.24–1.32), suggesting that these donated kidneys may have intrinsic predisposing factors for developing kidney disease. Part of this risk may be attributed to high-risk APOL1 alleles. Reeves-Daniel et al investigated the relationship between donor APOL1 risk variants and transplant survival after deceased donor kidney transplantation. The study included 136 kidneys from African American donors and their respective recipients, ~50% of whom were also African American. After accounting for global donor African ancestry, recipient age and sex, cold ischemia time, panel-reactive antibody, number of HLA antigen mismatches, and expanded criteria donation, the authors found that kidneys from African American deceased donors carrying 2 APOL1 risk alleles failed more rapidly posttransplantation than kidneys from deceased donors with 0 or 1 risk variant (hazard ratio, 3.84; P = 0.008). Differences in transplant survival based on APOL1 genotype distributions were evident 20 months posttransplantation. Of lost transplants with 2 APOL1 risk variants, 75% had biopsy-proven APOL1-associated lesions, including FSGS and/or arteriosclerosis, compared with 11.8% of lost transplants with 0 or 1 APOL1 risk allele.
In contrast to donor genotype, the presence of 2 APOL1 risk alleles in the recipient does not appear to be associated with decreased transplant survival. Lee et al investigated the impact of recipient APOL1 genotypes on transplant survival in 119 African American recipients. Approximately 38% of respective donors were African American. At 5 years posttransplantation, the rate of transplant loss was 22.4% in recipients carrying 2 APOL1 risk alleles compared to 21.3% in those with either 0 or 1 risk allele. In sum, these preliminary data suggest that APOL1 expression in the kidney is more relevant to kidney outcomes than systemic expression. Differences in transplant outcomes between kidneys from living and deceased donors with high-risk APOL1 alleles remain to be determined, especially with the potential role of ischemic injury in precipitating the initial kidney injury and differences in immunosuppressive regimens, including target trough levels of calcineurin inhibitors.
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