Nur-Sultan, Kerey, Zhanibek Khandar str., house 3
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Staged desensitizing therapy for complex preoperative preparation of candidates for organ (liver/kidney) transplantation with high immunological risk

 

Relevance

For patients with end-stage kidney and liver disease, kidney/liver transplantation is the gold standard of care, not only saving a life but also significantly improving quality of life. Patients with end-stage kidney/liver disease with a history of repeated pregnancies, blood transfusions, and organ/tissue transplants belong to a cohort of patients at high immunological risk. Highly sensitized transplant candidates face limited access to donor organs due to their high immunological risk. Sensitization is one of the main obstacles to the successful outcome of transplantation, often leading to antibody-mediated rejection. Many recipient sensitization cases are associated with an increase in the duration of waiting for a donor organ, which leads to exclusion from the waiting list due to the death of patients.

Nowadays desensitizing protocols are used in the world, including plasmapheresis sessions, administration of monoclonal antibodies, and intravenous immunoglobulin. However, in our republic, desensitizing protocols in organ transplantation are not used and have not been introduced into national protocols for organ transplantation. It was a prerequisite for the project for the scientifically based implementation of desensitizing protocols in our country.

Purpose of the project

To evaluate the effectiveness of desensitizing protocols in the complex preparation of candidates for transplantation, which will lead to an increase in the pool of donors for highly sensitized recipients.

Project objectives

  • To estimate the proportion of highly sensitized organ transplant candidates among the total number of patients.
  • To define criteria for including patients in the high immunological risk group.
  • To develop an algorithm for examining a recipient/donor in a group with a high immunological risk.
  • To determine indications for desensitization
  • To develop approaches to overcome the immunological barrier of recipients. To develop desensitizing protocols for patients at high immunological risk.
  • To evaluate the effectiveness of desensitizing protocols in liver/kidney transplantation in highly sensitized patients.
  • To estimate the incidence of hyperacute and acute rejection within two weeks after organ transplantation.

 

Expected results

  1. Reducing the immunological risk in patients on the waiting list and candidates for transplantation with an intravital and posthumous donor.
  2. Reducing the risk of hyperacute and acute rejection in renal/liver transplant recipients
  3. Improvement of graft and recipient survival rates after liver/kidney transplantation
  4. Publication of 3 articles in an international journal (impact factor 0.5-5.0; target journals Transplant International (impact factor-3.177, cite score percentile - 70) Transplantation Proceedings (impact factor-0.784. Cite score percentile-40%; Transplantation Reviews (impact factor-3.262. cite score percentile 81%)
  5. Publication of the article in editions recommended by CQAES MES RK (target journals – Clinical Medicine of Kazakhstan, Astana Medicine Journal)
  6. Based on the principles of evidence-based medicine as a result of the proposed project, the development, and implementation of a protocol for desensitization of kidney/liver recipients into the national protocols for kidney/liver transplantation
  7. Development and publication of a methodological manual on desensitization of candidates for organ transplantation with high immunological risk
  8. Conducting training seminars among transplant doctors on the effectiveness of the use of desensitizing protocols for a group of patients with high immunological risk.

 

Investigators

Abdrakhmanova Saniya, ORCID: 0000-0003-0782-1795 URL:  https://orcid.org/0000-0003-0782-1795

Asykbayev Mels Nurseitovich, ORCID: 0000-0003-2386-0997  URL: https://orcid.org/0000-0003-2386-0997

Abdugafarov Saitkarim Abdugapirovich, ORCID: 0000-0002-8393-9966 URL: https://orcid.org/0000-0002-8393-9966

Spatayev Zhanat Seitbatallovich, ORCID: 0000-0003-1659-431X URL: https://orcid.org/0000-0003-1659-431X

Zheksembayev Asan Aitmukashevich

Saparbay Jamilya Zhumabekovna, ORCID: 0000-0002-8478-5452 URL: https://orcid.org/0000-0002-8478-5452

Akhmetova Dana Meiram-Batyrovna

Zhakhina Gulnur Talgatovna, ORCID: 0000-0002-1001-1374 URL: https://orcid.org/0000-0002-1001-1374

Zhangaziyeva Kuralai, ORCID: 0000-0002-2005-006X URL: https://orcid.org/0000-0002-2005-006X

Turganbekova Aida, ORCID: 0000-0002-1514-5910 URL: https://orcid.org/0000-0002-1514-5910

Tuyakova Nurlygul, ORCID: 0000-0002-8987-0429 URL: https://orcid.org/0000-0002-8987-0429

Parkhomenko Elena Alexandrovna

Adilbayeva Aigerim Shahapovna

Zhanzakova Zhuldyz Zhetpisbayevna

 

 

 

Achieved results

For the period from March 2021 to November 2021, 19 patients with an established diagnosis of Chronic Kidney Disease (stages 4-5) were included in the study.

Of the 19 patients who were included in the study, at the stage of questioning and medical examination, one was excluded due to contraindications. When determining the compatibility of patients (cross-match) for desensitization by a blood test, 5 showed incompatibility with a potential donor, but after repeated cross-match with the DTT reagent, their results came out negative. The abovementioned patients underwent organ transplantation, they did not undergo the stages of desensitizing therapy. These patients were discharged without acute and hyperacute rejection, in satisfactory condition.

As a result, 13 patients were included in the desensitizing therapy, of which men (5) and women (8) accounted for 38.5% and 61.5%, respectively. The average age of the patients who were included in the study was 44.8 years, ranging from 25 to 58 years.

Although patients do not show a significant difference in the level of leukocyte antibodies after 1 stage of desensitizing therapy and one session of plasmapheresis, there is a significant decrease after repeated sessions of plasmapheresis.

List of scientific products for 2021:

 

  1. «Malignant neoplasm of renal allograft». Saparbay J. Report. VIII Congress of Oncologists and Radiologists, October 14-16, 2021, Turkestan, Kazakhstan.
  2. «Kidney transplantation: 10-year experience of LLP National Cancer Research Center». Asykbayev M. Report. VII Congress of Surgeons of Kazakhstan with International Participation «Surgery: yesterday, today, tomorrow». September 30 – October 1, 2021. Almaty.
  3. «Renal transplant carcinomas», Saparbay J. Report. VII Congress of Surgeons of Kazakhstan with International Participation «Surgery: yesterday, today, tomorrow». September 30 – October 1, 2021. Almaty.
  4. «Results of AB0 incompatible liver transplantation». Spatayev Zh. Report. VII Congress of Surgeons of Kazakhstan with International Participation «Surgery: yesterday, today, tomorrow». September 30 – October 1, 2021. Almaty.
  5. «The role of leukocyte antibodies in organ transplantation», poster presentation (Zhanzakova Zh., Abdrakhmanova S., Turganbekova A.). Sent to the V National Congress "The Globality of Nephrology: Priority Directions and Strategic Approaches", which will be held on November 19-20, 2021. G. Nur-Sultan, Kazakhstan.
  6. Saparbay J., Assykbayev M., Abdugafarov S., Zhakhina G., Spatayev Zh., Zhexembayev A., Zhanzakova Zh., Turganbekova A., Abdrakhmanova S., Kulkayeva G. (2021). Desensitization in kidney transplantation: review. Journal of Clinical Medicine of Kazakhstan.