Reacción a "Joint heart-kidney transplant tested in macaques to avoid rejection and immunosuppressants"

There are two fundamental limiting factors for the development of transplantation. On the one hand, the supply/demand disproportion, which is trying to be improved either by organisational measures or by the use of genetically modified animals, so far with little success. On the other hand, rejection remains the sword of Damocles for transplant recipients, and the immunosuppressive drugs available, apart from not being able to prevent it 100%, have a multitude of side effects, especially in the long term. Hence, one of the main avenues of current research is to achieve a state of ‘immunotolerance’: to ensure that the transplant recipient tolerates the organ as if it were his or her own and therefore does not need immunosuppressive drugs, or only in low doses, thus avoiding their harmful effects and achieving indefinite survival of the transplant.

This article is along these lines. One of the most studied procedures to achieve immunotolerance is to combine organ transplantation with a bone marrow or other form of haematopoietic progenitor transplant from the same donor preceded by preparative treatment. Promising results have been obtained with various abdominal organs, but not in cardiac transplantation, which raises many questions. What the authors have done using great apes as experimental animals is to transplant either a heart, or a heart associated with a kidney and bone marrow transplant from the same donor. Immunotolerance was induced only when the kidney was associated with the transplanted heart, a situation in which the animals did not experience rejection. 

In discussing the mechanisms by which this phenomenon could occur, which the authors call KICAT (kidney-induced cardiac allograft tolerance), they rule out a number of possibilities such as the erythropoietin produced by the kidney or a greater or lesser genetic similarity between donors and recipients, and conclude that it is due to the presence in the kidney of lymphatic structures rich in a type of T-regulatory cells that would not be present in the heart. Similar structures may explain why combined transplants involving the liver as one of the organs generate fewer rejections than those involving other organs in isolation.

The article represents an undoubtedly interesting experimental contribution to a better understanding of how to deal with immunotolerance in the clinic. Combined heart-kidney transplantation represents 5% of all heart transplants in North America (in Spain it is less than 1%) and therefore the authors propose the need for common protocols that allow for a deeper understanding of this phenomenon and improve results.