{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:53:02Z","timestamp":1787028782206,"version":"build-2736575974"},"reference-count":190,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"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>In recent decades, the rate of kidney transplantation has risen significantly, leading to better outcomes in terms of cardiovascular and overall mortality for patients with kidney failure. Although kidney transplantation represents the most effective therapeutic option, it is not devoid of the risk of failure. Immunological and non-immunological risk factors are involved. These factors often interact and may act synergistically, ultimately influencing graft longevity and patient survival. Both contribute to long-term transplant outcomes; however, non-immunological factors, representing a significant clinical challenge, will be the focus of our review. Of the numerous non-immunological risk factors, for clarity and to avoid overextending the discussion, only those most closely associated with chronic kidney disease have been considered: hypertension, anemia, diabetes mellitus, proteinuria, electrolyte and acid\u2013base imbalances, and impaired bone mineralization. Hypertension is reported in approximately 90% of kidney transplant recipients, often related to immunosuppressive therapy and residual renal dysfunction, and it is strongly associated with reduced graft survival. Anemia affects approximately 20\u201351% of these patients, contributing to cardiovascular morbidity and a more rapid decline in graft function, as does pre-existing diabetes mellitus. Proteinuria has a prevalence ranging from 7.5% to 45%, depending on the established target, and is a significant negative prognostic factor. Metabolic complications are also frequent; for example, hyperkalemia has an incidence of 25\u201344%, and metabolic acidosis has a prevalence of 12\u201358%. In our review, each of these factors is analyzed in terms of clinical impact, etiopathogenic mechanism, and available therapeutic management.<\/jats:p>","DOI":"10.3390\/life16020248","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:00:47Z","timestamp":1770033647000},"page":"248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ongoing and Novel Challenges in Kidney Transplantation: Therapeutic Approaches to Non-Immunological Risk Factors for Allograft Loss"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2168-702X","authenticated-orcid":false,"given":"Michele","family":"Provenzano","sequence":"first","affiliation":[{"name":"Nephrology, Dialysis and Renal Transplant Unit, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende-Hospital \u2018SS. Annunziata\u2019, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4092-1125","authenticated-orcid":false,"given":"Roberta","family":"Arena","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Renal Transplant Unit, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende-Hospital \u2018SS. Annunziata\u2019, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Renal Transplant Unit, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende-Hospital \u2018SS. Annunziata\u2019, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0220-1653","authenticated-orcid":false,"given":"Lilio","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Nephrology and Dialysis Unit, Ospedale Santa Maria delle Croci, AUSL Romagna, viale Randi 5, 48121 Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ruotolo","sequence":"additional","affiliation":[{"name":"Renal Unit, DAMSS, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Patella","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Renal Transplant Unit, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende-Hospital \u2018SS. Annunziata\u2019, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7600-524X","authenticated-orcid":false,"given":"Giuseppe","family":"Pezzi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosita","family":"Greco","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Renal Transplant Unit, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende-Hospital \u2018SS. Annunziata\u2019, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8226-6483","authenticated-orcid":false,"given":"Valeria","family":"Grandinetti","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8313-2492","authenticated-orcid":false,"given":"Rocco","family":"Malivindi","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Renal Transplant Unit, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende-Hospital \u2018SS. Annunziata\u2019, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3227-5573","authenticated-orcid":false,"given":"Michele","family":"Di Dio","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Renal Transplant Unit, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende-Hospital \u2018SS. Annunziata\u2019, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Baraldi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Nephrology and Dialysis Unit, Ospedale Santa Maria delle Croci, AUSL Romagna, viale Randi 5, 48121 Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4160-8840","authenticated-orcid":false,"given":"Giorgia","family":"Comai","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8532-0182","authenticated-orcid":false,"given":"Luca","family":"De Nicola","sequence":"additional","affiliation":[{"name":"Renal Unit, DAMSS, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1001\/jamainternmed.2025.5624","article-title":"Survival Benefits of Deceased Donor Kidney Transplant vs Waitlisting","volume":"185","author":"Zhu","year":"2025","journal-title":"JAMA Intern. 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