Deceased Donor Urinary Biomarker Signature and the Effectiveness of Peritransplant Lymphocyte Depletion on Early Renal Allograft Function

S. Bernd,² P. Heeger,¹ T-.P. Heather,³ I. Hall,⁷ M. Doshi,⁴ F. Weng,⁵ P. Reese,⁶ C. Parikh.³

¹Icahn School of Medicine Mount Sinai, New York, NY
²University of Ulm, Ulm, Germany
³Yale University School of Medicine, New Haven, CT
⁴Wayne State University, Detroit, MI
⁵Barnabas Health, Livingston, NJ
⁶University of Pennsylvania, Philadelphia, PA
⁷University of Utah School of Medicine, Salt Lake City, UT.

Meeting: 2018 American Transplant Congress

Abstract number: 217

Keywords: Induction therapy, Inflammation, Ischemia, Kidney transplantation

Session Information

Session Name: Concurrent Session: Kidney Immunosuppression: Induction Therapy

Session Type: Concurrent Session

Date: Monday, June 4, 2018

Session Time: 2:30pm-4:00pm

Presentation Time: 3:42pm-3:54pm

Location: Room 6C

Purpose: Delayed graft function (DGF) is associated with increased allogaft immunogenicity and decreased long-term survival. We hypothesized that high levels of donor urinary biomarkers for injury and inflammation amplify inflammation after reperfusion in recipients and that Thymoglobulin (Thymo) reduces reperfusion injury and risk of DGF.

Methods: In a multicenter prospective cohort, we collected urine samples from deceased donors at organ procurement for injury and inflammation biomarker measurements (IL-18, KIM-1, MCP-1, NGAL, C3a, C5a). We then recorded induction therapy and post-transplant outcomes for the 572 recipients of kidneys from these donors.

Results: Urinary biomarkers revealed the kidney injury and complement activation were common among deceased donors. 90% of the recipients received Thymo at a median dose of 5.8 mg/kg. When analyzed above or below median Thymo dose, higher Thymo dose was associated with DCD donor status, longer cold ischemia time, high cPRA. Thymo dose was not associated with a) recipient DGF, b) posttransplant renal function on day 7 and 12-months, or c) graft failure rate at 1 year. Thymo dose was also not associated with reduced DGF rate in organs with deceased donor acute injury (defined by AKIN). We noted significant interaction between the 2nd tertile of urinary C5a (and a trend for the 3rd tertile) and Thymo dose on the outcome of DGF. Compared to kidneys with lower C5a levels (1st tertile) the odds of DGF were higher with elevated C5a and the use of lower Thymo dose (2nd C5a tertile odds ratio 2.36; 95%CI 1.19-4.68; p=0.03; 3rd C5a tertile odds ratio 1.96; 95%CI 0.99-3.89) In contrast, individuals with a higher Thymo doses was not significantly associated with DGF regardless of donor C5a levels.

Conclusion: These data suggest that high levels of the urinary inflammatory biomarker C5a in donors amplifies the recipient inflammatory responses after reperfusion and that adequate Thymo dose reduce the rate of recipient DGF in this subgroup.

CITATION INFORMATION: Bernd S., Heeger P., Heather T-.P., Hall I., Doshi M., Weng F., Reese P., Parikh C. Deceased Donor Urinary Biomarker Signature and the Effectiveness of Peritransplant Lymphocyte Depletion on Early Renal Allograft Function Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Bernd S, Heeger P, Heather T-P, Hall I, Doshi M, Weng F, Reese P, Parikh C. Deceased Donor Urinary Biomarker Signature and the Effectiveness of Peritransplant Lymphocyte Depletion on Early Renal Allograft Function [abstract]. https://atcmeetingabstracts.com/abstract/deceased-donor-urinary-biomarker-signature-and-the-effectiveness-of-peritransplant-lymphocyte-depletion-on-early-renal-allograft-function/. Accessed November 21, 2024.

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