Use of polyclonal antibodies in brain-dead donors in kidney transplantation

Author:

Kuzmin D. O.1,Manukovsky V. A.2,Bagnenko S. F.3,Reznik O. N.4,Ananiev A. N.1,Vorobyeva O. A.5,Vorobyev S. L.5,Gogolev D. V.1,Daineko V. S.6,Kutenkov A. A.1,Chichagova N. A.1,Uliankina I. V.1

Affiliation:

1. St. Petersburg Research Institute of Emergency Medicine; Pavlov First St. Petersburg State Medical University

2. St. Petersburg Research Institute of Emergency Medicine

3. Pavlov First St. Petersburg State Medical University

4. St. Petersburg Research Institute of Emergency Medicine; Pavlov First St. Petersburg State Medical University; North-Western State Medical University

5. National Center for Clinical Morphological Diagnostics

6. St. Petersburg Research Institute of Emergency Medicine; North-Western State Medical University

Abstract

Objective. The objective of this study is to develop a therapeutic strategy for protecting grafts in order to improve the efficiency of kidney transplantation (KT) using polyclonal antibodies (pAbs) through elimination of activated forms of neutrophils, chemo- and cytokines from the donor’s bloodstream, and a decrease in the level of expression of adhesion molecules on the renal vascular endothelium at the pre-transplant stage.Materials and methods. In 2017, we developed and for the first time applied a therapeutic strategy for ischemia-reperfusion injury (IRI) in a brain-dead donor (BDD). Given the limited time interval after brain death has been diagnosed, Timoglobulin (Sanofi Genzyme, France) was administered to the donor at a dose of 8 mg/kg intravenously for 6 hours. Before drug administration and immediately before the start of cold perfusion, a complete blood count and renal transplant biopsy were performed. The study group included 10 BDDs (mean age 39.3 ± 4.4 years) who received anti-thymocyte globulin (ATG). The comparison group included 10 BDDs (mean age 38.5 ± 4.3 years) who did not undergo the new strategy. Donor kidneys were transplanted to 40 recipients (average age 47.5 ± 4.3 years), who were also divided into 2 groups, depending on the graft received (with and without ATG). At the organ donation center, a biobank of specimens from donors of various categories, including those using the IRI therapeutic strategy and recipients for retrospective assessment of the effectiveness of pAbs, was formed.Results. Clinical blood test results show that in the ATG group, there was stable leukopenia (neutropenia and lymphopenia) of 1.46 ± 0.18x109/l. Fifteen (75%) recipients of kidneys obtained from donors with ATG had immediate graft function; in the control group – 10 (50%) recipients.Conclusion. Data obtained testify to the prospects of implementing the proposed strategy in clinical practice, which will improve the quality of the resulting grafts and their suitability for subsequent transplantation, prolong graft functioning due to elimination of leukocytes as a factor of IRI, prevention of early allograft nephropathy, increase in the donor pool by using expanded criteria donors (ECDs).

Publisher

V.I. Shimakov Federal Research Center of Transplantology and Artificial Organs

Subject

Transplantation,Immunology and Allergy

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