Abstract: TH-PO605

CMV Infection as a Trigger for APOL1-Associated Collapsing FSGS in Renal Allograft

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Dale, Leigh-Anne, Columbia University Medical Center, New York, New York, United States
  • Husain, Syed Ali, Columbia University Medical Center, New York, New York, United States
  • Chang, Jae Hyung, Columbia University Medical Center, New York, New York, United States
  • Crew, Russell J., Columbia University , New York, New York, United States
  • Cohen, David J., Columbia University, New York, New York, United States
  • Chiles, Mariana C., Columbia University Medical Center, New York, New York, United States
  • Li, Yifu, Columbia University, New York, New York, United States
  • Gharavi, Ali G., Columbia University, New York, New York, United States
  • Mohan, Sumit, Columbia University, New York, New York, United States
Background

Apolipoprotein L1 gene (APOL1) risk alleles are associated with increased risk of focal segmental glomerulosclerosis (FSGS) in patients with 2 risk alleles (G1 or G2) compared to those with at least 1 wild type allele (G0). The mechanisms of APOL1-mediated renal disease remain unclear. While 13% of African Americans (AA) carry two APOL1 risk alleles and only a minority of these individuals develop kidney disease, this appears to contribute to inferior allograft outcomes with kidneys transplanted from AA donors. We present 2 cases of FSGS in transplanted kidneys from a donor with 2 APOL1 risk alleles.

Methods

The donor was a 57-year-old AA man with a history of hypertension who died from a stroke. Recipient 1 was a 47-year-old AA woman with diabetes-associated end stage renal disease (ESRD). Post-reperfusion biopsy was notable for mild focal global glomerulosclerosis. Post-operative course was notable for delayed graft function (DGF), and a nadir creatinine (SCr) of 1.6mg/dL. She subsequently developed proteinuria (6.7g/g) and elevated SCr (3.7) 7 months post-transplant in the setting of a diarrheal illness secondary to cytomegalovirus (CMV) infection. Viremia cleared with reduced immunosuppression. Repeat biopsy for persistent proteinuria showed tubular injury, and collapsing FSGS that led to allograft failure 18 months post-transplant.
Recipient 2 was a 64-year-old Caucasian woman with ESRD from polycystic kidney disease. Post-operative course was notable for DGF, with a nadir SCr of 1.3mg/dL. She developed CMV viremia and colitis 12 months post-transplant that was followed by SCr rising to 2.9mg/dl with 7.6g/g proteinuria. Renal biopsy showed acute tubular injury and collapsing FSGS. Viremia cleared after mycophenolic acid was discontinued and ganciclovir was initiated. Allograft failed 14 months after transplant.
While both the donor (G1/G1) and recipient 1 (G1/G1) had 2 APOL1 risk variants, recipient 2 (G0/G0) did not have any risk alleles.

Conclusion

This suggests that the genetic susceptibility for APOL1-related lesions is linked to the presence of donor risk alleles. Additionally, CMV infection appears to be a second hit resulting in the development of collapsing FSGS after transplant in kidneys with 2 risk alleles.