Podocyte density is reduced in kidney allografts with high-risk APOL1 genotypes at transplantation

Dhruti P. Chen, Ziad S. Zaky, Jesse D. Schold, Leal C. Herlitz, Rasha El-Rifai, Paul E. Drawz, Leslie A. Bruggeman, Laura Barisoni, Susan L. Hogan, Yichun Hu, John F. O’Toole, Emilio D. Poggio, John R. Sedor

Research output: Contribution to journalArticlepeer-review

Abstract

Variants in apolipoprotein L1 (APOL1) gene are associated with nondiabetic kidney diseases in black subjects and reduced kidney transplant graft survival. Living and deceased black kidney donors (n = 107) were genotyped for APOL1 variants. To determine whether allografts from high-risk APOL1 donors have reduced podocyte densities contributing to allograft failure, we morphometrically estimated podocyte number, glomerular volume, and podocyte density. We compared allograft loss and eGFR trajectories stratified by APOL1 high-risk and low-risk genotypes. Demographic characteristics were similar in high-risk (n = 16) and low-risk (n = 91) donors. Podocyte density was significantly lower in high-risk than low-risk donors (108 ± 26 vs 127 ± 40 podocytes/106um3, P =.03). Kaplan-Meier graft survival (high-risk 61% vs. low-risk 91%, p-value = 0.049) and multivariable Cox models (hazard ratio = 2.6; 95% CI, 0.9-7.8) revealed higher graft loss in recipients of APOL1 high-risk allografts over 48 months. More rapid eGFR decline was seen in recipients of high-risk APOL1 allografts (P <.001). At 60 months, eGFR was 27 vs. 51 mL/min/1.73 min2 in recipients of APOL1 high-risk vs low-risk kidney allografts, respectively. Kidneys from high-risk APOL1 donors had worse outcomes versus low-risk APOL1 genotypes. Lower podocyte density in kidneys from high-risk APOL1 donors may increase susceptibility to CKD from subsequent stresses in both the recipients and donors.

Original languageEnglish (US)
Article numbere14234
JournalClinical Transplantation
Volume35
Issue number4
DOIs
StatePublished - Apr 2021

Bibliographical note

Funding Information:
This study was supported by grants from the NIH, R01 DK108329, and R01 DK097836. DPC was supported by training grant DK007470. We thank Dr. Roger Wiggins for his contributions and thoughtful discussions on carrying out morphometric methodology and analysis for podocyte density.

Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

  • disparities
  • kidney donor
  • outcomes
  • podometrics
  • transplant

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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