Two studies show the way ahead for better non-invasive monitoring of kidney transplants
Members of the Kidney-affecting Diseases Research Group and the Innovation in Vesicles and Cells for Application in Therapy (REMAR-IVECAT) have recently published two studies led by Dr Francesc E. Borràs, which identify possible biomarkers of irreversible damage to transplanted kidneys; a pathology that eventually causes them to stop working. The papers have been published in the International Journal of Molecular Science and the Journal of Nephrology.
Kidney transplant is a life-saving procedure for many patients, but it also brings high risks. Patients must take immune-suppressive drugs to avoid their own immune system attacking the new organ. Many pathogenic processes can take place, in the worst case leading to a hardening of kidney tissue, called fibrosis, that can lead to the kidney no longer working. There is an acute need for non-invasive ways to monitor transplanted kidneys, ideally from urine samples to help doctors monitor these patients.
The REMAR-IVECAT groups at the Germans Trias i Pujol Hospital and Research Institute have been working on technology to bring this about using the information condensed in tiny capsules called extracellular vesicles (EVs). EVs are released by cells into body fluids and contain proteins, which can act as a snapshot of the condition of the tissue they came from.
In the first paper the group used EVs to look for signs of kidney damage caused by Calcineurin inhibitors (CNI), a commonly used immune-suppressant, which is effective but can have serious side effects. They compared patients taking CNI with normal kidney function with a group with damage caused by CNI and a third group with another type of damage to the grafted kidney. "This is a pilot study, meaning we looked at small number of patients," says Laura Carreras-Planella, first author on the studies. "Our results show that the EVs in urine are potential biomarkers to detect and monitor the rate of damage in kidney-transplanted patients," she adds.
In the second paper the group identified vitronectin as a possible stand-alone biomarker to monitor fibrotic stages in kidney transplant patients. "These are important early results," explains Borràs. "They show that our techniques for purifying and analyzing the proteins in these tiny vesicles is a potentially powerful way to identify molecules that allow us to monitor the kidneys of these patients and we can carry out this analysis from easily obtained urine samples. Such a test would help doctors monitor kidney transplant patients much better and identify problems much earlier on. We will be continuing our work in the laboratory and with our colleagues in the hospital to further refine and validate these tests for routine use with patients."
Proteomic Characterization of Urinary Extracellular Vesicles from Kidney-Transplanted Patients Treated with Calcineurin Inhibitors. Laura Carreras-Planella et al. Int J Mol Sci. 2020 Oct; 21(20): 7569. Published online 2020 Oct 14. doi: 10.3390/ijms21207569 PMCID: PMC7589460 PMID: 33066346
Urinary vitronectin identifies patients with high levels of fibrosis in kidney grafts. Carreras-Planella L, Cucchiari D, Cañas L, Juega J, Franquesa M, Bonet J, Revuelta I, Diekmann F, Taco O, Lauzurica R, Borràs FE. J Nephrol. 2020 Dec 4. doi: 10.1007/s40620-020-00886-y. Online ahead of print.PMID: 33275196
This work was supported in part by grants from project PI13/00050 integrated in the National R+D+I and funded by the ISCIII and the European Regional Development Fund (http://www.isciii.es), the SGR program of Generalitat de Catalunya (2017-SGR-301 REMAR Group), the ISCIII-REDinREN (RD16/0009 Feder Funds), and Fundació Cellex. The project leading to these results has also received funding from "la Caixa" Foundation (ID 100010434), under agreement CI19-00048. This activity has received funding from the European Institute of Innovation and Technology (EIT). This body of the European Union receives support from the European Union's Horizon 2020 research and innovation program. LCP is sponsored by the Spanish Government FPU grant ("Formación de Personal Universitario", FPU17/01444). MF is supported by ISCIII (MS19/00018), co-funded by ERDF/ESF, "Investing in your future". FEB is a researcher from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, supported by the Health Department of the Catalan Government (Direcció General de Recerca i Innovació, Dept. Salut, Generalitat de Catalunya).