The APOL1 Gene and Allograft Survival after Kidney Transplantation
| Autor: | John A. DePalma, Patricia L. Adams, Barry I. Freedman, Pamela J. Hicks, Mariana Murea, Michael D. Gautreaux, Carl D. Langefeld, Jen Jar Lin, Donald W. Bowden, Amber Reeves-Daniel, Michael V. Rocco, Anthony J. Bleyer, Robert J. Stratta, David F. Kiger, Jasmin Divers |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Risk medicine.medical_specialty Pathology Genotype Apolipoprotein L1 Kidney Gastroenterology Nephropathy HLA Antigens Internal medicine medicine Humans Transplantation Homologous Immunology and Allergy Pharmacology (medical) Renal Insufficiency Kidney transplantation Proportional Hazards Models Transplantation biology Glomerulosclerosis Focal Segmental Donor selection business.industry Graft Survival Hazard ratio Middle Aged medicine.disease Kidney Transplantation HLA Mismatch Tissue Donors Black or African American Apolipoproteins Multivariate Analysis biology.protein Female Lipoproteins HDL business Immunosuppressive Agents Follow-Up Studies Kidney disease |
| Zdroj: | American Journal of Transplantation. 11:1025-1030 |
| ISSN: | 1600-6135 |
| DOI: | 10.1111/j.1600-6143.2011.03513.x |
| Popis: | Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with nephropathy in African Americans (AAs). The effect of transplanting kidneys from AA donors with two APOL1 nephropathy risk variants is unknown. APOL1 risk variants were genotyped in 106 AA deceased organ donors and graft survival assessed in 136 resultant kidney transplants. Cox-proportional hazard models tested for association between time to graft failure and donor APOL1 genotypes. The mean follow-up was 26.4 ± 21.8 months. Twenty-two of 136 transplanted kidneys (16%) were from donors with two APOL1 nephropathy risk variants. Twenty-five grafts failed; eight (32%) had two APOL1 risk variants. A multivariate model accounting for donor APOL1 genotype, overall African ancestry, expanded criteria donation, recipient age and gender, HLA mismatch, CIT and PRA revealed that graft survival was significantly shorter in donor kidneys with two APOL1 risk variants (hazard ratio [HR] 3.84; p = 0.008) and higher HLA mismatch (HR 1.52; p = 0.03), but not for overall African ancestry excluding APOL1. Kidneys from AA deceased donors harboring two APOL1 risk variants failed more rapidly after renal transplantation than those with zero or one risk variants. If replicated, APOL1 genotyping could improve the donor selection process and maximize long-term renal allograft survival. |
| Databáze: | OpenAIRE |
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