Abstract: TH-PO009

Complement Factor D, a New Predictor of Renal Allograft Dysfunction and Rejection?

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Daniel, Christoph, University Erlangen-Nürnberg, Erlangen, Germany
  • Bobka, Steffen, FAU Erlangen-Nürnberg, Erlangen, Germany
  • Buettner, Maike Julia, FAU Erlangen-Nürnberg, Erlangen, Germany
  • Amann, Kerstin U., FAU Erlangen-Nürnberg, Erlangen, Germany
Background

The complement system is part of innate immunity and thus important for graft function and survival. Here we focused on complement Factor D (CFD) that initiates alternative complement activation by cleavage of factor B. Triggers of CFD upregulation are unknown and it is unclear if CFD is already upregulated in zero-biopsies of transplanted kidneys. In addition, we assessed whether the alternative complement pathway is upregulated in the setting of delayed graft function.

Methods

CFD was investigated in renal zero- and corresponding transplant-biopsies of patients receiving a cadaveric kidney transplant using immunohistochemistry. Specimens were selected from patients with delayed graft function (DGF, n=12), T-cell mediated rejection (TCMR, n=10) and antibody mediated rejection (ABMR, n=8) and evaluated with regard to localization and degree of expression of CFD. Furthermore, renal complement factor D reactivity was correlated with renal function and transplantation conditions.

Results

CFD was located in different compartments of renal transplants. In 0-biopsies prominent CFD-staining was found in tubules in comparable amounts in all investigated groups. In contrast, glomerular CFD reactivity in 0-biopsies was at least 4-times lower compared to tubular staining but showed significant differences between groups. Highest glomerular CFD was detected in patients that later develop ABMR, being about 5-times higher compared to 0-biopsies from patients that developed DGF. Interestingly, CFD staining was prominent in glomerular, tubular and interstitial localization in post-transplant biopsies without clear differences between groups. The amount of glomerular CFD in 0-biopsies strongly correlated with renal changes including glomerulitis (r=0.628; p<0.001), chronic transplant glomerulopathy (r=0.659; p<0.001) and mesangial matrix expansion (r=0.771; p<0.001) in transplant-biopsies taken after at a later timepoint. Furthermore, donor serum creatinine correlated with tubular CFD in post-transplant biopsies (r=0.463; p=0.006).

Conclusion

CFD is upregulated in DGF and in antibody as well as T-cell mediated rejection compared to zero-biopsies. Our findings implicate CFD reactivity in 0-biopsies as a potentially useful predictor of pathophysiologic changes in transplanted kidneys in the post-transplantation time course.

Funding

  • Government Support - Non-U.S.