Integrating APOL1 Gene Variants Into Renal Transplantation: Considerations Arising From the American Society of Transplantation Expert Conference

Thirteen percent of individuals of African ancestry express two variant copies of the gene encoding apolipoprotein 1 (APOL1) that has been associated with an increased risk of end‐stage renal disease (ESRD) in the general population. Limited studies suggest that the survival of transplanted kidneys from donors expressing two APOL1 risk alleles is inferior to that of kidneys from donors with zero or one risk allele. In living kidney donation, two case reports describe donors expressing two APOL1 risk alleles who developed ESRD. Given the potential impact of APOL1 variants on the utility and safety of kidney transplantation and living kidney donation, the American Society of Transplantation convened a meeting with the goals of summarizing the current state of knowledge with respect to transplantation and APOL1, identifying knowledge gaps and studies to address these gaps, and considering approaches to integrating APOL1 into clinical practice. The authors recognize that current data are not sufficient to support traditional evidence‐based guidelines but also recognize that it may require several years to generate the necessary data. Thus, approaches as to how APOL1 might currently be integrated into the clinical decision‐making process were considered. This report summarizes the group's deliberations.

[1]  E. Gordon,et al.  APOL1‐Associated End‐Stage Renal Disease in a Living Kidney Transplant Donor , 2016, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[2]  J. Cooper,et al.  APOL1 Polymorphisms in a Deceased Donor and Early Presentation of Collapsing Glomerulopathy and Focal Segmental Glomerulosclerosis in Two Recipients , 2016, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[3]  J. Coresh,et al.  Race, APOL1 Risk, and eGFR Decline in the General Population. , 2016, Journal of the American Society of Nephrology : JASN.

[4]  Nicholette D. Palmer,et al.  APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors , 2016, Transplantation.

[5]  B. Astor,et al.  Examination of Potential Modifiers of the Association of APOL1 Alleles with CKD Progression. , 2015, Clinical journal of the American Society of Nephrology : CJASN.

[6]  L. Riella,et al.  Testing for High-Risk APOL1 Alleles in Potential Living Kidney Donors. , 2015, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[7]  Nicholette D. Palmer,et al.  Apolipoprotein L1 Gene Variants in Deceased Organ Donors Are Associated With Renal Allograft Failure , 2015, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[8]  G. Knoll,et al.  APOL1 Genotyping of African American Deceased Organ Donors: Not Just Yet , 2015, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[9]  Sophie Limou,et al.  APOL1 Kidney Disease Risk Variants: An Evolving Landscape. , 2015, Seminars in nephrology.

[10]  B. Freedman,et al.  Should kidney donors be genotyped for APOL1 risk alleles? , 2015, Kidney international.

[11]  A. Israni,et al.  OPTN/SRTR 2013 Annual Data Report: Deceased Organ Donation , 2015, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[12]  A. Israni,et al.  OPTN/SRTR 2013 Annual Data Report: Kidney , 2015, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[13]  D. Segev,et al.  Survival Benefit of Primary Deceased Donor Transplantation With High‐KDPI Kidneys , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[14]  O. Gribouval,et al.  APOL1 polymorphisms and development of CKD in an identical twin donor and recipient pair. , 2014, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[15]  S. Gabriel,et al.  Increased Burden of Cardiovascular Disease in Carriers of APOL1 Genetic Variants , 2014, Circulation research.

[16]  Mei-Cheng Wang,et al.  Risk of end-stage renal disease following live kidney donation. , 2014, JAMA.

[17]  John D Reveille,et al.  End‐Stage Renal Disease in African Americans With Lupus Nephritis Is Associated With APOL1 , 2014, Arthritis & rheumatology.

[18]  G. Genovese,et al.  The APOL1 Genotype of African American Kidney Transplant Recipients Does Not Impact 5‐Year Allograft Survival , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[19]  V. D’Agati,et al.  APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy. , 2011, Journal of the American Society of Nephrology : JASN.

[20]  A. Ashley-Koch,et al.  MYH9 and APOL1 are both associated with sickle cell disease nephropathy , 2011, British journal of haematology.

[21]  C. Young,et al.  African American living-kidney donors should be screened for APOL1 risk alleles. , 2011, Transplantation.

[22]  Giulio Genovese,et al.  APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. , 2011, Journal of the American Society of Nephrology : JASN.

[23]  M. Rocco,et al.  The APOL1 Gene and Allograft Survival after Kidney Transplantation , 2011, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[24]  C. Winkler,et al.  The apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy in African Americans. , 2010, Journal of the American Society of Nephrology : JASN.

[25]  C. Winkler,et al.  Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans , 2010, Science.

[26]  S. Rosset,et al.  Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene , 2010, Human Genetics.

[27]  Scott M. Williams,et al.  The Genetic Structure and History of Africans and African Americans , 2009, Science.

[28]  D. Reich,et al.  MYH9 is associated with nondiabetic end-stage renal disease in African Americans , 2008, Nature Genetics.

[29]  D. Vlahov,et al.  MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis , 2008, Nature Genetics.

[30]  A. Garg,et al.  Living Kidney Donors Requiring Transplantation: Focus on African Americans , 2007, Transplantation.

[31]  R. Foley,et al.  Longitudinal study of racial and ethnic differences in developing end-stage renal disease among aged medicare beneficiaries. , 2007, Journal of the American Society of Nephrology : JASN.

[32]  N. Powe,et al.  Excess risk of chronic kidney disease among African-American versus white subjects in the United States: a population-based study of potential explanatory factors. , 2002, Journal of the American Society of Nephrology : JASN.

[33]  B. Kiberd,et al.  Cumulative risk for developing end-stage renal disease in the US population. , 2002, Journal of the American Society of Nephrology : JASN.

[34]  P. Whelton,et al.  End-stage renal disease in African-American and white men. 16-year MRFIT findings. , 1997, JAMA.

[35]  A. Chandraker The Real World Impact of APOL1 Variants on Kidney Transplantation. , 2016, Transplantation.