{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:34:41Z","timestamp":1788568481148,"version":"build-2803163510"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01EO0802"],"award-info":[{"award-number":["01EO0802"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,2]]},"abstract":"\n Background<\/jats:title>\n Pharmacokinetic monitoring is insufficient to estimate the intensity of immunosuppression after transplantation. Virus-specific T cells correlate with both virus-specific and general cellular immune defense. Additional steering of immunosuppressive therapy by virus-specific T cell levels might optimize dosing of immunosuppressants.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In a multicenter, randomized, controlled trial, we randomized 64 pediatric kidney recipients to a control group with trough-level monitoring of immunosuppressants or to an intervention group with additional steering of immunosuppressive therapy by levels of virus-specific T cells (quantified by cytokine flow cytometry). Both groups received immunosuppression with cyclosporin A and everolimus in the same target range of trough levels. Primary end point was eGFR 2 years after transplantation.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In the primary analysis, we detected no difference in eGFR for the intervention and control groups 2 years after transplantation, although baseline eGFR 1 month after transplantation was lower in the intervention group versus the control group. Compared with controls, patients in the intervention group received significantly lower daily doses of everolimus and nonsignificantly lower doses of cyclosporin A, resulting in significantly lower trough levels of everolimus (3.5 versus 4.5\n \u00b5<\/jats:italic>\n g\/L,\n P<\/jats:italic>\n <0.001) and cyclosporin A (47.4 versus 64.1\n \u00b5<\/jats:italic>\n g\/L,\n P<\/jats:italic>\n <0.001). Only 20% of patients in the intervention group versus 47% in the control group received glucocorticoids 2 years after transplantation (\n P<\/jats:italic>\n =0.04). The groups had similar numbers of donor-specific antibodies and serious adverse events.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Steering immunosuppressive therapy by virus-specific T cell levels in addition to pharmacokinetic monitoring seems safe, results in a similar eGFR, and personalizes immunosuppressive therapy by lowering exposure to immunosuppressive drugs, likely resulting in lower drug costs.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n IVIST trial, https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/search?query=2009-012436-32 and ISRCTN89806912<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2020050645","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T14:17:47Z","timestamp":1617286667000},"page":"502-516","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":23,"title":["Steering Transplant Immunosuppression by Measuring Virus-Specific T Cell Levels: The Randomized, Controlled IVIST Trial"],"prefix":"10.1681","volume":"32","clinical-trial-number":[{"clinical-trial-number":"nct89806912","registry":"10.18810\/clinical-trials-gov","type":"results"},{"clinical-trial-number":"isrctn89806912","registry":"10.18810\/isrctn","type":"results"}],"author":[{"given":"Thurid","family":"Ahlenstiel-Grunow","sequence":"first","affiliation":[{"name":"Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany"},{"name":"Department of Pediatrics II, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Biostatistics, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Schild","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, University Hospital Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, University Hospital Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Taylan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Children\u2019s and Adolescents\u2019 University Hospital, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz T.","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Children\u2019s and Adolescents\u2019 University Hospital, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagen","family":"Staude","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, University Children\u2019s Hospital, University Hospital of Rostock, Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murielle","family":"Verboom","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Department of Pharmacovigilance, Institute for Clinical Pharmacology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxandra","family":"Sabau","sequence":"additional","affiliation":[{"name":"Department of Pharmacovigilance, Institute for Clinical Pharmacology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Gro\u00dfhennig","sequence":"additional","affiliation":[{"name":"Institute of Biostatistics, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Pape","sequence":"additional","affiliation":[{"name":"Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany"},{"name":"Department of Pediatrics II, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"B1-20240826","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1056\/NEJMoa031643","article-title":"Long-term survival of children with end-stage renal disease","volume":"350","author":"McDonald","year":"2004","journal-title":"N Engl 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