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Kidney Week

Abstract: FR-OR134

Accelerated Podocyte Detachment Early after Kidney Transplantation and Relationship to Long-Term Allograft Loss-of-Function

Session Information

Category: Transplantation

  • 1802 Transplantation: Clinical

Authors

  • Naik, Abhijit S., University of Michigan, Ann Arbor, Michigan, United States
  • Afshinnia, Farsad, University of Michigan, Ann Arbor, Michigan, United States
  • Aqeel, Jawad, University of Michigan, Ann Arbor, Michigan, United States
  • Cibrik, Diane M., University of Kansas, Kansas city, Kansas, United States
  • Samaniego-Picota, Milagros D., Henry Ford Hospital, Detriot, Michigan, United States
  • Wickman, Larysa T., University of Michigan, Ann Arbor, Michigan, United States
  • Wang, Su Qing, University of Michigan, Ann Arbor, Michigan, United States
  • Chowdhury, Mahboob A., University of Michigan, Ann Arbor, Michigan, United States
  • Wiggins, Roger C., University of Michigan, Ann Arbor, Michigan, United States
Background

Kidney allograft half-life has not improved despite excellent short-term survival. Recent long-term surveillance biopsy studies identify accumulating glomerulosclerosis associated with late allograft loss. While podocyte depletion is well-known to drive proteinuria and glomerulosclerosis in animal models and human glomerular diseases, its role in renal allograft loss-of-function is not generally recognized.

Methods

To address these questions, we collected urine from 125 kidney transplant recipients in the first post-transplant year for urine pellet mRNA and protein analysis, with a median follow up of 4.5-years.

Results

Using multivariable linear models adjusted for proteinuria, transplant, recipient and donor factors, we observed that the average rate of podocyte detachment in the first post-transplant year was significantly associated with eGFR decline. The relationship between podocyte detachment rate and eGFR decline persisted even among recipients who were non-proteinuric (<0.3g/g creatinine) and who had no recurrent or de novo glomerular disease identified on 1yr protocol biopsy.

Conclusion

These findings support the concept that in kidney allografts accelerated podocyte loss precedes proteinuria, is associated with inferior long-term allograft outcomes as measured by eGFR decline. Modulating factors driving early podocyte detachment after kidney transplantation may help improve long-term outcomes.

Predictors of eGFR slope over median 4.5 years of follow-up: Multivariable analysis.
Variableß Coef.Std. ErrP valueLCLUCL
Log UPodCR-2.170.620.001-3.41-0.93
Log UProtCR0.150.590.81-1.031.33
GGS >10%
(ref: GGS <10 %)
-4.201.650.01-7.50-0.94
Glomerular Disease (TG or Recurrent disease)-5.772.040.006-9.83-1.70

Adjusted for recipient & donor factors (age,race,sex, race,BSA), transplant factors (HLA mismatch, cold ischemia time), first year events (de novo DSA and rejection), average of other urine mRNA markers (UTGFbeta1CR,UAqp2CR) and IFTA. Abbreviations: UpodCR, urine podocin mRNA to urine creatinine ratio; UAqp2CR, urine aquaporin2 mRNA to urine ratio; UTGFbeta1CR, urine transforming growth factor beta mRNA to creatinine, UProtCR; urine protein to creatinine ratio.

Funding

  • NIDDK Support