{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:16:20Z","timestamp":1790972180371,"version":"4.1.0"},"reference-count":220,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Chronic kidney disease is rising worldwide, and kidney transplantation remains the preferred modality of kidney replacement therapy. However, long-term graft survival continues to be limited by chronic alloimmune injury, particularly antibody-mediated rejection (ABMR) and its chronic active form. This narrative review synthesizes contemporary evidence on the immunopathogenesis, epidemiology, diagnosis, and management of kidney allograft rejection, with a deliberate focus on studies from the last five years and on United States and European cohorts. We summarize current concepts of T cell\u2013mediated rejection (TCMR), ABMR, mixed and donor-specific antibody (DSA)\u2013negative phenotypes, and the evolution of the Banff classification, highlighting how chronic active ABMR has emerged as a leading cause of death-censored graft loss. We then critically appraise the conventional diagnostic triad of creatinine\/eGFR, DSA, and biopsy and review emerging tools, including donor-derived cell-free DNA, urinary chemokines such as CXCL9 and CXCL10, additional blood- and urine-based biomarkers, and biopsy transcriptomics. We also examine how artificial intelligence and machine learning may support digital pathology, multimodal risk prediction, and data integration, while recognizing the current challenges of biological interpretability, external validation, and clinical implementation. Finally, we propose a rejection-focused precision-medicine framework and outline key research gaps, including multicenter validation, trial-ready endpoints, and governance for AI-enabled pathways. Overall, the field is moving from isolated diagnostic signals toward integrated, biologically informed, and clinically actionable approaches to rejection detection and risk stratification.<\/jats:p>","DOI":"10.3390\/life16040674","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T09:15:59Z","timestamp":1776244559000},"page":"674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Rejection-Focused Precision Medicine in Kidney Transplantation: Biology, Biomarkers, and Artificial Intelligence"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8911-3380","authenticated-orcid":false,"given":"Luis","family":"Ramalhete","sequence":"first","affiliation":[{"name":"Blood and Transplantation Center of Lisbon, Instituto Portugu\u00eas do Sangue e da Transplanta\u00e7\u00e3o, Alameda das Linhas de Torres, n\u00b0 117, 1769-001 Lisbon, Portugal"},{"name":"NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"iNOVA4Health\u2014Advancing Precision Medicine, N\u00facleo de Investiga\u00e7\u00e3o em Doen\u00e7as Renais, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"LBS\u2014Lisbon Business & Government School, Rua de S\u00e3o Bernardo, 34-A, 1200-427 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9369-6486","authenticated-orcid":false,"given":"R\u00faben","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0528-2716","authenticated-orcid":false,"given":"Miguel Bigotte","family":"Vieira","sequence":"additional","affiliation":[{"name":"NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"iNOVA4Health\u2014Advancing Precision Medicine, N\u00facleo de Investiga\u00e7\u00e3o em Doen\u00e7as Renais, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"Servi\u00e7o de Nefrologia, Nova Medical School, Hospital Curry Cabral, Unidade Local de Sa\u00fade de S\u00e3o Jos\u00e9, 1050-099 Lisbon, Portugal"},{"name":"Centro Cl\u00ednico Acad\u00e9mico de Lisboa, 1169-024 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4525-9062","authenticated-orcid":false,"given":"Emanuel","family":"Vigia","sequence":"additional","affiliation":[{"name":"NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"iNOVA4Health\u2014Advancing Precision Medicine, N\u00facleo de Investiga\u00e7\u00e3o em Doen\u00e7as Renais, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"LBS\u2014Lisbon Business & Government School, Rua de S\u00e3o Bernardo, 34-A, 1200-427 Lisbon, Portugal"},{"name":"Centro Cl\u00ednico Acad\u00e9mico de Lisboa, 1169-024 Lisbon, Portugal"},{"name":"Hepatobiliopancreatic and Transplantation Center, Curry Cabral Hospital, Unidade Local de Sa\u00fade de S\u00e3o Jos\u00e9, R. da Benefic\u00eancia 8, 1050-099 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5264-9755","authenticated-orcid":false,"given":"Cec\u00edlia R. C.","family":"Calado","sequence":"additional","affiliation":[{"name":"ISEL\u2014Instituto Superior de Engenharia de Lisboa, Rua Conselheiro Em\u00eddio Navarro 1, 1959-007 Lisbon, Portugal"},{"name":"Institute for Bioengineering and Biosciences (iBB), The Associate Laboratory Institute for Health and Bioeconomy-i4HB, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3300-6033","authenticated-orcid":false,"given":"Anibal","family":"Ferreira","sequence":"additional","affiliation":[{"name":"NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"iNOVA4Health\u2014Advancing Precision Medicine, N\u00facleo de Investiga\u00e7\u00e3o em Doen\u00e7as Renais, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"},{"name":"Servi\u00e7o de Nefrologia, Nova Medical School, Hospital Curry Cabral, Unidade Local de Sa\u00fade de S\u00e3o Jos\u00e9, 1050-099 Lisbon, Portugal"},{"name":"Centro Cl\u00ednico Acad\u00e9mico de Lisboa, 1169-024 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","unstructured":"GBD Chronic Kidney Disease Collaboration (2020). 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