{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:52:34Z","timestamp":1760143954406,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,10]],"date-time":"2024-03-10T00:00:00Z","timestamp":1710028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud","award":["RD21\/0005\/0016","PI 18\/01704","PI 18\/01832","PI 23\/01909"],"award-info":[{"award-number":["RD21\/0005\/0016","PI 18\/01704","PI 18\/01832","PI 23\/01909"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria del Instituto de Salud Carlos III","award":["RD21\/0005\/0016","PI 18\/01704","PI 18\/01832","PI 23\/01909"],"award-info":[{"award-number":["RD21\/0005\/0016","PI 18\/01704","PI 18\/01832","PI 23\/01909"]}]},{"name":"Spanish Society of Transplantation and a Diaverum Spain","award":["RD21\/0005\/0016","PI 18\/01704","PI 18\/01832","PI 23\/01909"],"award-info":[{"award-number":["RD21\/0005\/0016","PI 18\/01704","PI 18\/01832","PI 23\/01909"]}]},{"name":"VHIR (Vall Hebron Institute of Research)","award":["RD21\/0005\/0016","PI 18\/01704","PI 18\/01832","PI 23\/01909"],"award-info":[{"award-number":["RD21\/0005\/0016","PI 18\/01704","PI 18\/01832","PI 23\/01909"]}]},{"name":"Catalan Society of Transplantation","award":["RD21\/0005\/0016","PI 18\/01704","PI 18\/01832","PI 23\/01909"],"award-info":[{"award-number":["RD21\/0005\/0016","PI 18\/01704","PI 18\/01832","PI 23\/01909"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Subclinical inflammation in protocol biopsies relates to tacrolimus exposure and human leukocyte antigen (HLA) matching. We aimed to characterize transcripts associated with rejection and tacrolimus exposure and the latter\u2019s association with transplant outcomes. We tested whether gene expression is associated with rejection using strictly normal protocol biopsies (n = 17) and biopsies with T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR) according to Banff criteria (n = 12). Subsequently, we analyzed these transcripts in a set of 4-month protocol biopsies (n = 137) to assess their association with donor and recipient characteristics, the intensity of immunosuppression, and the graft outcome. Differential expression (false discovery rate (FDR) &lt; 0.01, fold (change (FC) &gt; 3) between normal and rejection biopsies yielded a set of 111 genes. In the protocol biopsy cohort (n = 137), 19 out of these 111 genes correlated with tacrolimus trough levels at the time of biopsy (TAC-C0), and unsupervised analysis split this cohort into two clusters. The two clusters differed in donor age and tacrolimus trough levels. Subclinical rejection, including borderline lesions, tended to occur in the same cluster. Logistic regression analysis indicated that TAC-C0 at the time of biopsy (OR: 0.83, 95%CI:0.72\u20130.06, p = 0.0117) was associated with cluster 2. In a follow-up averaging 70 \u00b1 30 months, this patient group displayed a significant decline in renal function (p = 0.0135). The expression of rejection-associated transcripts in early protocol biopsies is associated with tacrolimus exposure and a faster decline in renal function.<\/jats:p>","DOI":"10.3390\/ijms25063189","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T06:05:30Z","timestamp":1710137130000},"page":"3189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Expression of Rejection-Associated Transcripts in Early Protocol Renal Transplant Biopsies Is Associated with Tacrolimus Exposure and Graft Outcome"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4267-2273","authenticated-orcid":false,"given":"Betty","family":"Chamoun","sequence":"first","affiliation":[{"name":"Nephrology Department, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Department of Medicine, Autonomous University of Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina B.","family":"Torres","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Department of Medicine, Autonomous University of Barcelona, 08035 Barcelona, Spain"},{"name":"Laboratory of Nephrology and Transplantation, Vall d\u2019Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"Gabald\u00f3n","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9016-7506","authenticated-orcid":false,"given":"Thomas","family":"Jouv\u00e9","sequence":"additional","affiliation":[{"name":"Laboratory of Nephrology and Transplantation, Vall d\u2019Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain"},{"name":"Renal Transplant Unit, Nephrology Department, Grenoble University Hospital, 38043 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Meneghini","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Laboratory of Nephrology and Transplantation, Vall d\u2019Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M.","family":"Z\u00fa\u00f1iga","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Laboratory of Nephrology and Transplantation, Vall d\u2019Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joana","family":"Sellar\u00e9s","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Laboratory of Nephrology and Transplantation, Vall d\u2019Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manel","family":"Perell\u00f3","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Ser\u00f3n","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oriol","family":"Bestard","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Department of Medicine, Autonomous University of Barcelona, 08035 Barcelona, Spain"},{"name":"Laboratory of Nephrology and Transplantation, Vall d\u2019Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7267-3963","authenticated-orcid":false,"given":"Francesc","family":"Moreso","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Department of Medicine, Autonomous University of Barcelona, 08035 Barcelona, Spain"},{"name":"Laboratory of Nephrology and Transplantation, Vall d\u2019Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/00007890-199401001-00009","article-title":"Histological finding in early routine protocol biopsies in renal transplantation","volume":"57","author":"Rush","year":"1994","journal-title":"Transplantation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1097\/00007890-199502270-00012","article-title":"Sequential protocol biopsies in renal transplant patients. 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