{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T05:10:56Z","timestamp":1793250656050,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sociedad Madrile\u00f1a de Trasplante"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sodium-glucose co-transporter 2 inhibitors (SGLT2i) preserve cardiac and renal function by mechanisms that are not completely elucidated. Among other things, SGLT2i promote nutrient-deprivation signalling, which might affect the immune function. As the fate of immune cells is controlled by their metabolism, we aimed to study the mitochondrial integrity of lymphocytes isolated from renal transplant recipients with type 2 diabetes (T2D) upon SGLT2i therapy instauration and six-month follow up. In this real-world pilot study, the mitochondrial respiration of isolated peripheral blood mononuclear cells was monitored in a Seahorse XFp extracellular-flux analyzer and cells were photographed with a confocal microscope. Mitochondrial mass, membrane potential, and superoxide content of lymphocyte subpopulations were measured by flow cytometry (MitoTrackerTM Green, TMRM, and MitoSOXTM Red probes). Leveraging in vivo conditions of immune cells, we evaluated their metabolic profiles associated with immune activation. Herein, we identified changes in redox homeostasis with sustained membrane polarization, and an increased mitochondrial biogenesis upon PHA stimulation that significantly correlated with changes in body weight and LDL-cholesterol levels, and a resultant compensatory mitochondrial function of lymphocytes. Our data suggest novel mechanisms induced by SGLT2i to modulate immune cells, which probably underlie the observed beneficial effects in kidney transplant recipients. Nonetheless, further mechanistic studies are required to extend these exploratory findings and encourage the use of this therapeutic strategy.<\/jats:p>","DOI":"10.3390\/ijms26073351","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T06:52:56Z","timestamp":1743749576000},"page":"3351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mitochondrial Changes Induced by SGLT2i in Lymphocytes from Diabetic Kidney Transplant Recipients: A Pilot Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4644-1277","authenticated-orcid":false,"given":"Isabel","family":"P\u00e9rez-Flores","sequence":"first","affiliation":[{"name":"Nephrology Department, Health Research Institute of Hospital Cl\u00ednico San Carlos (IdISSC), Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea R.","family":"L\u00f3pez-Pastor","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Cl\u00ednico San Carlos (IdISSC), 28040 Madrid, Spain"},{"name":"Cooperative Research Networks Oriented to Health Results (RICORS, REI), 28089 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3097-5557","authenticated-orcid":false,"given":"Ulises","family":"G\u00f3mez-Pinedo","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Advanced Therapy, Health Research Institute of Hospital Cl\u00ednico San Carlos (IdISSC), Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"G\u00f3mez-Infantes","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Cl\u00ednico San Carlos (IdISSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Espino-Pais\u00e1n","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Cl\u00ednico San Carlos (IdISSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-4816","authenticated-orcid":false,"given":"Natividad","family":"Calvo Romero","sequence":"additional","affiliation":[{"name":"Nephrology Department, Health Research Institute of Hospital Cl\u00ednico San Carlos (IdISSC), Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6529-2735","authenticated-orcid":false,"given":"M. Angeles","family":"Moreno de la Higuera","sequence":"additional","affiliation":[{"name":"Nephrology Department, Health Research Institute of Hospital Cl\u00ednico San Carlos (IdISSC), Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8272-0356","authenticated-orcid":false,"given":"Beatriz","family":"Rodr\u00edguez-Cubillo","sequence":"additional","affiliation":[{"name":"Nephrology Department, Health Research Institute of Hospital Cl\u00ednico San Carlos (IdISSC), Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9734-8788","authenticated-orcid":false,"given":"Irene","family":"G\u00f3mez-Delgado","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Cl\u00ednico San Carlos (IdISSC), 28040 Madrid, Spain"},{"name":"Cooperative Research Networks Oriented to Health Results (RICORS, REI), 28089 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7017-9729","authenticated-orcid":false,"given":"Ana I.","family":"S\u00e1nchez-Fructuoso","sequence":"additional","affiliation":[{"name":"Nephrology Department, Health Research Institute of Hospital Cl\u00ednico San Carlos (IdISSC), Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Department of Medicine, Medical School, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8470-8396","authenticated-orcid":false,"given":"Elena","family":"Urcelay","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Cl\u00ednico San Carlos (IdISSC), 28040 Madrid, Spain"},{"name":"Cooperative Research Networks Oriented to Health Results (RICORS, REI), 28089 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N. 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