Donor's APOL1 Risk Genotype and "Second Hits" Associated With De Novo Collapsing Glomerulopathy in Deceased Donor Kidney Transplant Recipients: A Report of 5 Cases

Am J Kidney Dis. 2019 Jan;73(1):134-139. doi: 10.1053/j.ajkd.2018.05.008. Epub 2018 Jul 25.

Abstract

The presence of 2 APOL1 risk variants (G1/G1, G1/G2, or G2/G2) is an important predictor of focal segmental glomerulosclerosis (FSGS) and chronic kidney disease in individuals of African descent. Although recipient APOL1 genotype is not associated with allograft survival, kidneys from deceased African American donors with 2 APOL1 risk variants demonstrate shorter graft survival. We present a series of cases of presumed de novo collapsing FSGS in 5 transplanted kidneys from 3 deceased donors later identified as carrying 2 APOL1 risk alleles, including 2 recipients from the same donor whose kidneys were transplanted in 2 different institutions. Four of these recipients had viremia in the period preceding the diagnosis of collapsing FSGS. Cytomegalovirus and BK virus infection were present in 3 and 1 of our 5 cases, respectively, around the time that collapsing FSGS occurred. We discuss viral infections, including active cytomegalovirus infection, as possible "second hits" that may lead to glomerular injury and allograft failure in these recipients. Further studies to identify additional second hits are necessary to better understand the pathologic mechanisms of donor APOL1-associated kidney disease in the recipient.

Keywords: Apolipoprotein L1 (APOL1); BK virus; allograft failure; case reports; collapsing FSGS; cytomegalovirus (CMV); deceased donor; donor genotype; end-stage renal disease (ESRD); focal segmental glomerulosclerosis (FSGS); genotype; kidney biopsy; kidney transplant outcome; polyomavirus; risk variant; second hit; viral infection; viremia.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Apolipoprotein L1 / genetics*
  • Donor Selection
  • Female
  • Genotype
  • Glomerulosclerosis, Focal Segmental / genetics*
  • Graft Survival
  • Humans
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Postoperative Complications / genetics*
  • Risk Factors
  • Treatment Failure

Substances

  • APOL1 protein, human
  • Apolipoprotein L1