What has ADP-ribose polymerases activity got to do with tubular necrosis in a kidney that is going to be transplanted? A lot, according to the indications of these studies, and its temporary inhibition could improve the functional nature of these organs once they have been transplanted. In this sense, the Department of Pathological Anatomy and Science History of the UGR, in collaboration with the team of Francisco Javier Oliver, of the CSIC (Higher Council of Scientific Research) keeps studying ADP-ribose polymerases, an enzyme that gets activated to a greater or lesser extent in every donor and which also depends on the time of cold ischemia (time interval that begins when an organ is cooled after organ procurement surgery and ends when the organ is implanted).
Currently, most donors are adults. Most of them are valid organs to be transplanted, but all the cases are assessed through a microscope by the pathologist before being implanted. However, some of them fail a few days after in the new organism. The final aim of these studies is to prevent these failures. The paper which is going to be published before the end of the year in the international journal Transplantation Proceeding is based on the study of more than 150 cases, mostly Cuban, “as they have problems to transplant a kidney immediately. The delay can exceed the 24 hours in many cases. It involves more damage for the renal graft and the alteration of its function once it has been transplanted”, Francisco O´Valle Ravassa, the first author of the work, explains.
Immediate activation
When we see a newly removed fragment, tubular necrosis can not be observed. It is needed some time to obtain the morphological data, between 12 and 24 hours. But, if an enzyme gets immediately activated, it can be an indication of that there is something wrong with that kidney, to intervene before it stops working. ADP ribose polymerases will help us to solve this problem as this enzyme gets immediately activated when it detects cell damage and it could be useful to predict renal behaviour once transplanted.
Acute tubular necrosis usually appears between five and eleven days after the transplant. In these cases, the rate ADP-ribose enzyme is higher than in sound kidneys and, of course, young ones completely sound, which are not very common in transplants. Tubular necrosis can be eventually got over, with support measures, such as haemodialysis.
The aim is to cancel the activity of this enzyme which takes part in the necrosis induction. But this is unthinkable. “This enzyme is known as the yin-yang”, O´Valle explains, “as it takes part in essential processes for living organisms, such as in repairing DNA damage”. Researchers have started to consider applying inhibiting substances of the activity of this enzyme in the preservation liquids of the kidneys to be transplanted. This is a feasible idea, contrasted with essays carried out with animal models, and it does not involve the enzyme inhibition, which resumes its normal activity once the kidney has been transplanted.
Reference:
Prof. Francisco O´Valle Ravassa
Dpt. Pathological Anatomy and Science History.
E-mail: fovalle@ugr.es
Phone number: 958246180 – 958243512.
Mobile: 610638804