Collaboration across the continuum of care to improve equity for highly sensitized people in kidney transplantation

Highly sensitized patients and the challenge of organ compatibility

People with ESRD are considered highly sensitized when they have high levels of pre-formed donor specific antibodies (DSA).^8,9 These antibodies can trigger an immune response against a transplanted organ and cause tissue damage and potentially transplant rejection.^9,10 The presence of DSAs at the time of transplantation is a barrier to kidney transplantation.^5,9,10 People who have had previous blood transfusions or organ transplants and women who have been pregnant are at risk of being highly sensitized.^5-9

People who are highly sensitized face extended, and often indefinite, time on the transplant waiting list due to the complexity of their immunological profile that makes the identification of a suitable donor organ significantly more difficult.^5,6,11,12

Improving equity in organ allocation for highly sensitized patients

Although recent improvements in transplantation technique and organ allocation have brought an increase in organ transplantation,^13,14 highly sensitized individuals still face inequity in access to transplantation and are often dependent on dialysis for years, which impacts their quality and length of life and remains a costly approach to managing ESRD.^15,16

Currently, those classified as highly sensitized account for approximately 10-15 percent of total patients on the transplant waiting lists in the US and Europe.¹⁷ Ensuring these people have equitable access to organ donation and transplantation requires stakeholders from across the healthcare continuum to work together.

Prioritizing immunologically complex patients’ access to care  

As those that are highly sensitized languish on transplant wait list, their condition continues to progress. However, with desensitization strategies in place, they can and should be considered for transplantation. Programs and initiatives that help identify highly sensitized patients who have spent significant time on the transplant wait list are key to ensuring these individuals have access to desensitization strategies that could result in the successful identification of a suitable organ for a kidney transplant. 

A recent example of this is the Desensitization Program created by Eurotransplant (ET), a non-profit organization that helps facilitate the allocation and exchange of suitable organs for transplantation across seven EU countries.

ET’s Desensitization Program is the first ever international allocation system designed to enable kidney transplantation in highly sensitized patients with a very low chance of transplantation. The program is an additional component to ET’s Acceptable Mismatch (AM) program aimed at identifying those highly sensitized who have been on the wait list for more than 5 years without being able to receive a successful transplant.

To date, five highly sensitized transplant candidates have been identified and received a suitable kidney for transplant through the Desensitization Program.

Embedding guideline directed care and international consensus on desensitization strategies

As science advances and innovative new approaches to desensitization in kidney transplantation become available, new clinical guidelines are needed. Over the last four years, the clinical community and influential professional societies have recognized and taken up the charge to establish more consistent approaches to desensitization thus enabling kidney transplantation for highly sensitized patients.

In fact, since 2020 Hansa has collaborated with the European Society for Organ Transplantation (ESOT) and convened key transplant community thought leaders to identify and align on the challenges of desensitization, patient prioritization schemes, and agree on opportunities to increase access to transplantation for highly sensitized kidney transplant candidates, including the appropriate use of innovative new desensitization strategies.

In 2022, ESOT published the first set of clinical guidelines representing the first international consensus on a management pathway for highly sensitized patients.¹⁸ The guidelines serve as a foundation for country-specific guidelines and consensus across Europe.

Healthcare policy as a catalyst to improve equity and patient outcomes

Equitable access to transplantation needs to be embedded within healthcare policy frameworks in each country to ensure success.

In the European Union, work is underway to create a new EU Action Plan on Organ Donation and Transplantation. This Action Plan may give the EU an opportunity to harmonize approaches to transplantation among countries, improve coordination, and increase the number of transplant recipients.

The work is being championed by the European Kidney Health Alliance (EKHA) whose recent Kidney Manifesto for the EU calls for: improvements to the primary and secondary prevention of kidney disease; improved organ donation and transplantation; and for the EU to support innovation in kidney therapies.¹⁹ Critically the call to action on transplantation is the development and implementation of a new EU Action Plan on Organ Donation and Transplantation. We believe the implementation of the action plan, embedded in EU and ultimately Member State healthcare policy, would ensure more equitable access for currently underserved patients, including highly sensitized kidney transplant patients.

“The recently elected EU Parliament must ensure that kidney health is a key priority. Chronic kidney disease is the fastest rising cause of death, and if we don’t act now chronic kidney disease will be the 5th leading cause of death by 2050.”, said Professor Raymond Vanholder, EKHA President. “To mitigate this burden, one of the options is creating a new EU Action Plan on Organ Donation and Transplantation to drive forward change in transplantation. We look forward to working with the Hungarian EU Presidency during second semester of 2024 to move this forward and ensure the new Action Plan is created and implemented.”

Delivering on our commitment to ensure access to transplantation care for highly sensitized kidney transplant patients

We are pleased to see so many important and influential stakeholders prioritize kidney health and, more importantly, kidney transplantation and allocation particularly with highly sensitized patients in mind. We know that delivering great medicines in transplantation is not enough. 

We commend the patient, policy and clinical communities for their continued efforts to ensure equity in care for highly sensitized kidney transplant patients, including the use of desensitization strategies, and improving access to organ allocations. 

References

1. Vanholder, Raymond, et al. "Fighting the unbearable lightness of neglecting kidney health: the decade of the kidney." Clinical kidney journal 14.7 (2021): 1719-1730
2. NIH (2018). What is kidney failure? Available at: https://www.niddk.nih.gov/health-information/kidney-disease/kidney-failure/what-is-kidney-failure. Last accessed: July 2024.
3. Centre for Disease Control and Prevention, “Chronic Kidney Disease in the United States, 2023”: https://www.cdc.gov/kidney-disease/media/pdfs/CKD-Factsheet-H.pdf. Last accessed: July 2024.
4. Axelrod DA, et al. An economic assessment of contemporary kidney transplant practice. Am J Transplant. 2018 May;18(5):1168-1176. doi: 10.1111/ajt.14702. Epub 2018 Mar 31. PMID: 29451350.
5. Alelign T, Ahmed MM, Bobosha K, Tadesse Y, Howe R, Petros B. Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies. J Immunol Res. 2018 Mar 5;2018:5986740. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859822/
6. Heidt S, et al. Highly Sensitized Patients are Well Serves by Recieving a Compatible Organ Offer Based on Acceptable Mismatches. Front Immunol. 2021;12:687254. Available at: https://pubmed.ncbi.nlm.nih.gov/34248971/
7. Newsletter Transplant 2022. International figures on donation and transplantation. Available at: Newsletter Transplant - latest edition I Freepub (edgm.eu) Last accessed: July 2024.
8. Mamode N, et al. European Guideline for the Management of Kidney Transplant Patients With HLA Antibodies: By the European Society for Organ Transplantation Working Group. Transpl Int. 2022 Aug 10;35:10511. Available at: https://pubmed.ncbi.nlm.nih.gov/36033645/
9. Eurostam Report (A Europe-wide strategy to enhance transplantation of highly sensitized patients on the basis of acceptable HLA mismatches.) Available at https://cordis.europa.eu/project/id/305385/reporting.
10. Lonze BE, et al. IdeS (Imlifidase): A Novel Agent That Cleaves Human IgG and Permits Successful Kidney Transplantation Across High-strength Donor-specific Antibody. Ann Surg. 2018 Sep;268(3):488-496. doi: 10.1097/SLA.0000000000002924. PMID: 30004918.
11. Jordan SC, et al. Imlifidase Desensitization in Crossmatch-positive, Highly Sensitized Kidney Transplant Recipients: Results of an International Phase 2 Trial (Highdes). Transplantation. 2021 Aug 1;105(8):1808-1817. doi: 10.1097/TP.0000000000003496.
12. ESOT Transplantation Learning Journey Highlights 15-17 November 2020-pg 25. Available at https://esot.org/scientific-highlights-transplantation-learning-journey-tlj-2-0/ Last accessed: July 2024.
13. Thongprayoon C, et al. Progress and Recent Advances in Solid Organ Transplantation. J Clin Med. 2022 Apr 11;11(8):2112. doi: 10.3390/jcm11082112. PMID: 35456205; PMCID: PMC9031939.
14. Bouwman, Renée, et al. "Study on the uptake and impact of the EU Action Plan on Organ Donation and Transplantation (2009-2015) in the EU Member States." European Commission (2017).
15. Canaud B, Kooman JP, Selby NM, Taal MW, Francis S, Maierhofer A, Kopperschmidt P, Collins A, Kotanko P. Dialysis-Induced Cardiovascular and Multiorgan Morbidity. Kidney Int Rep. 2020 Sep 9;5(11):1856-1869. Available at: https://pubmed.ncbi.nlm.nih.gov/33163709/
16. Redfield RR, et al. The mode of sensitization and its influence on allograft outcomes in highly sensitized kidney transplant recipients. Nephrol Dial Transplant. 2016 Oct;31(10):1746-53. doi: 10.1093/ndt/gfw099. Epub 2016 Jul 6. PMID: 27387475.
17. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2022 Annual Data Report. U.S. Department of Health and Human Services, Health Resources and Services Administration; 2024. Last accessed: July 2024.
18. European Guidelines for the Management of Kidney Transplant Patients with HLA antibodies. https://esot.org/wp-content/uploads/2022/07/WS06_Full-doc_07202022.pdf. Last accessed: July 2024.
19. European Kidney Health Alliance “Kidney Manifesto An EU strategy to improve kidney care during the 2024-2029 mandate”. Available at: https://ekha.eu/wp-content/uploads/2024/01/EKHA_Kidney-Manifesto2024.pdf. Accessed: June 2024.