Klotho, HMGB-1 and Kynurenine as Marker for Injury and Function in Renal Transplantation

M. Stangl,¹ D. Abendroth.²

¹Transplant Center Munich, Klinikum Großhadern, LMU Munich, Munich, Germany
²Surgery, University of Ulm, Ulm, Germany.

Meeting: 2018 American Transplant Congress

Abstract number: D175

Keywords: Graft survival, Monitoring, Nephron mass, Protective genes

Session Information

Session Name: Poster Session D: Kidney Living Donor: Selection

Session Type: Poster Session

Date: Tuesday, June 5, 2018

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall 4EF

Brain death is associated with immune activation and tissue injuries, counter regulated by activation of the tryptophan pathway producing kynurenine (Kyn). High mobility group box 1 (HMGB1) is a nuclear factor released as an early mediator of repair, inflammation and destruction. Klotho (Kl) is a putative aging-suppressor and deficiency is involved in acute kidney injury and chronic kidney disease. Kyn suppresses T-cell reactivity upregulated by the pro-inflammatory cytokines IFN-γ and TNF-α. In a retrospective study, we investigated the role of HMGB1, Kyn and Kl in renal transplantation to estimate their influence on immediate and long-term graft-function.

Patients and Methods

A consecutive group of patients after renal transplantation (n=143) were included (mean age 41+11 y., duration of dialysis 40+23 months). Furthermore, sera from 97 organ donors (mean age 38,4+12 y.) could be evaluated.

Results

Significant elevation of HMGB1 in donors led to delayed graft function (DGF). HMGB1 was positive correlated (r²=0,718) to the days until creatinine drop < 200[micro]mol/l (9,66+10 (PF) vs. 25,8+14 (DGF);p<.001). Low Klotho in donor sera (-3s) led to significant lower 60 months graft survival und inferior graft function. Sustained elevation of Kyn in the sera of recipients between week 3 and 7 post transplant led to a significant lower 10 year graft survival (31% vs 71%)

ATG-induction treatment decreased HMGB-1 significantly (p<.001) by – 87% (+11) compared to standard immunosuppression (TDT) with an increase of + 24% (+9).

Conclusion

Kyn is a functional counter-regulator of innate immune response and showed an excellent correlation to rejection and long term-function. Elevated HMGB-1 indicates the grade of graft injury. Treatment with ATG is of benefit concerning DGF and long-term function. Klotho is a predictive marker of graft injury and long term graft function, better than donor creatinine.

CITATION INFORMATION: Stangl M., Abendroth D. Klotho, HMGB-1 and Kynurenine as Marker for Injury and Function in Renal Transplantation Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Stangl M, Abendroth D. Klotho, HMGB-1 and Kynurenine as Marker for Injury and Function in Renal Transplantation [abstract]. https://atcmeetingabstracts.com/abstract/klotho-hmgb-1-and-kynurenine-as-marker-for-injury-and-function-in-renal-transplantation/. Accessed May 16, 2025.

« Back to 2018 American Transplant Congress