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

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.

Figure 1.. Summary of clinical course by recipient.

Recipient A1 had a course complicated by multiple episodes of acute kidney injury and one episode of CMV viremia seven months after transplant. Biopsy at 14 months showed collapsing FSGS, followed by allograft failure at 17.5 months. Recipient A2 had a course complicated by CMV viremia at 12 months, followed by biopsy showing collapsing FSGS at 14 months with immediate graft failure. Recipient B1 developed persistent BK viremia at 15 months; biopsy at 21 months showed collapsing FSGS, and allograft failure occurred at 22 months. Recipient B2 had early AMR but no BK or CMV viremia. Biopsy at 19 months showed collapsing FSGS, with allograft failure at 23 months. Recipient C1 had CMV viremia at 7.5 months, with AKI due to collapsing FSGS, followed by complete renal recovery.

Figure 2.. Representative glomeruli from recipients B1 and B2.

Light microscopy of representative glomeruli from recipients B1 (silver stain, 400× magnification) and B2 (PAS stain, 400× magnification) demonstrating collapsing FSGS.