International Study Characterises for the First Time a New Type of Kidney Transplant Rejection

In cases of kidney failure, transplantation is the treatment of choice. However, the risk of rejection remains high. A better understanding of the immune response to kidney transplant rejection – and in particular the phenomenon of microvascular inflammation – could contribute to improved diagnostic and therapeutic management of patients. A study conducted by researchers from Inserm, AP-HP and Université Paris Cité, [1], in collaboration with international partners, has characterized for the first time new forms of kidney transplant rejection and their impact on long-term kidney graft survival. The results were published on October 24 in the New England Journal of Medicine (NEJM). 

Kidney transplantation is the treatment of choice for patients with end-stage renal disease, but its long-term success is compromised by rejection, the main cause of graft loss. Microvascular inflammation, a key indicator of the immune response during renal transplant rejection, represents a major challenge for clinicians. This as yet poorly characterized phenotype can manifest itself in a variety of clinical contexts, making the diagnostic and therapeutic management of patients particularly complex.

In a vast international study coordinated by Alexandre Loupy [1], professor at Paris Cité University, nephrologist in the adult nephrology-renal transplantation department at Necker-Enfants malades Hospital (AP-HP) and director of the Paris Institute for Transplantation and Organ Regeneration – PITOR at Paris Cité University), including 16,000 biopsies taken from 7,000 kidney transplant patients in 30 reference centers in 7 countries across Europe and North America, the researchers characterized for the first time new forms of kidney transplant rejection and their impact on long-term kidney graft survival.

The unique cohort formed as part of this research reflects the diversity of clinical practice across several countries, reinforcing the scope of the findings and their potential to influence transplant care worldwide. The integration of these new phenotypes in the diagnosis of rejection paves the way for standardization of future clinical trials, aimed at elucidating the underlying immunological processes and defining personalized therapeutic strategies.

“This research represents a major advance in kidney transplant medicine, for optimized patient management. In addition, these results open up significant avenues to better elucidate the mechanisms of organ rejection, with spin-offs in other fields such as cardiac, liver, lung and composite tissue transplantation, as well as xenotransplantation, where our team recently demonstrated similar rejection mechanisms involving the microcirculation,” says Professor Alexandre Loupy.

This study also highlights the need for large-scale projects to foster innovation in the management and follow-up of transplant patients, at a time when improving graft survival is essential to meet the global challenge of organ shortage.

[1] This project was led by a consortium of researchers from the Institut National de la Santé et de la Recherche Médicale (Inserm), AP-HP and Université Paris Cité, under the direction of Professor Alexandre Loupy of the Institut de Transplantation et de Régénération d’Organes de Paris (PITOR). This work was made possible thanks to support from the ANR (KTD-Innov study, ANR-17-RHUS-0010) as well as the Horizon Europe 2020 (EU-TRAIN study, 754995) and ERC Consolidator Grant (AI-Care, 101126272) programmes.

[2] NCT06496269

Source

Microvascular Inflammation of Kidney Allografts and Clinical Outcomes

Marta Sablik^*, Aurélie Sannier^*, Marc Raynaud^#, Valentin Goutaudier^#, Gillian Divard, Brad C. Astor, Patricia Weng, Jodi Smith, Rouba Garro, Bradley A. Warady, Rima S. Zahr, Katherine Twombley, Vikas R. Dharnidharka, Raja S. Dandamudi, Marc Fila, Edmund Huang, Anne-Laure Sellier-Leclerc, Burkhard Tönshoff, Marion Rabant, Jérôme Verine, Arnaud del Bello, Thierry Berney, Olivia Boyer, Rusan Ali Catar, Richard Danger, Magali Giral, Daniel Yoo, François Girardin, Alaa Alsadi, Pierre-Antoine Gourraud, Emmanuel Morelon, Moglie Le Quintrec, Mélanie Try, Jean Villard, Weixiong Zhong, Oriol Bestard, Klemens Budde, Bertrand Chauveau, Lionel Couzi, Sophie Brouard, Julien Hogan, Christophe Legendre, Dany Anglicheau, Olivier Aubert, Nassim Kamar, Carmen Lefaucheur, Alexandre Loupy

New England Journal of Medicine, 24 octobre 2024