Donor-Derived Cell-Free DNA (dd-cfDNA) in Kidney Transplant Recipients With Indication Biopsy: Results of a Prospective Single-Center Trial

Results

Background: Novel biomarkers are needed to improve management of kidney transplant recipients.During kidney injury, collagen type VI formation increases.The C-terminal fragment from the alpha3 chain (endotrophin) is released during formation and promotes inflammation and fibrosis.In the Eurostars (Eureka) funded consortium, PRO-C6-Rec, we investigated endotrophin in nine transplant cohorts from three European countries to obtain a comprehensive insight on the ability of this fragment to predict disease progression.
Methods: We analyzed plasma endotrophin with the PRO-C6 ELISA in nine transplant cohorts from three European countries.In incident kidney transplant recipients (KTR), levels were investigated both before and after transplantation, and the association with both acute (delayed graft function and rejection) and long-term outcomes (graft failure and mortality) was investigated.Relevant clinical variables were used to adjust the associations of endotrophin with the investigated outcomes.

Conclusions:
We show that the pro-fibrotic and pro-inflammatory molecule endotrophin is markedly increased in plasma of patients known to have increased risk of outcome, and that endotrophin is an independent predictor of clinically relevant outcomes, likely related to kidney fibrosis and inflammation.
Funding: Government Support -Non-U.S. Background: Donor-derived cell-free DNA (dd-cfDNA) is a marker of allograft injury in kidney transplant recipients (KTR).Little is known about the possible use of dd-cfDNA in evaluating response to anti-rejection treatment.

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Methods: This far, we enrolled 84 KTR with indication biopsy between November 2020 and May 2022.Besides routine transplant laboratory, AlloSeq dd-cfDNA was quantified at time of biopsy and on days 7, 30, and 90 following biopsy.
Conclusions: dd-cfDNA significantly discriminates active rejection at time of biopsy in KTR.Decreasing levels of dd-cfDNA may indicate treatment response in patients with ABMR and TCMR.dd-cfDNA may further help to identify borderline changes with favorable outcome from changes where additional therapy and closer monitoring is needed.

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Transplantation: Clinical -Biomarkers The Gut Microbiome Links to Metabolic Syndrome Following Kidney Transplantation Peter J. Mannon, Roslyn B. Mannon.University of Nebraska Medical Center, Omaha, NE.
Background: The metabolic syndrome (MBS) contributes to cardiovascular morbidity and mortality following kidney transplantation.Gut microbiome dysbiosis impacts lipid metabolism, insulin resistance, atherosclerotic factors, and in kidney transplant recipients (KTRs), may be linked to alloimmunity.We hypothesized that changes in gut microbiome pre-and post-transplant are linked to the outcome of MBS in KTRs.
Methods: Stool specimens (pre and 6-12 months post) from 14 serial KRTs from living donors and 8 healthy controls had 16S rRNA gene sequencing, microbial metagenome analysis, and targeted (69 gut metabolites in serum and 104 fecal