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Lorant, Tomas
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Publications (10 of 45) Show all publications
Nordling, S., Brännström, J., Carlsson, F., Lu, B., Salvaris, E., Wanders, A., . . . Magnusson, P. U. (2018). Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: Preclinical investigations in pig and mouse. Scientific Reports, 8, Article ID 5220.
Open this publication in new window or tab >>Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: Preclinical investigations in pig and mouse
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 5220Article in journal (Refereed) Published
Abstract [en]

Ischemia reperfusion injury is one of the major complications responsible for delayed graft function in kidney transplantation. Applications to reduce reperfusion injury are essential due to the widespread use of kidneys from deceased organ donors where the risk for delayed graft function is especially prominent. We have recently shown that coating of inflamed or damaged endothelial cells with a unique heparin conjugate reduces thrombosis and leukocyte recruitment. In this study we evaluated the binding capacity of the heparin conjugate to cultured human endothelial cells, to kidneys from brain-dead porcine donors, and to murine kidneys during static cold storage. The heparin conjugate was able to stably bind cultured endothelial cells with high avidity, and to the renal vasculature of explanted kidneys from pigs and mice. Treatment of murine kidneys prior to transplantation reduced platelet deposition and leukocyte infiltration 24 hours post-transplantation, and significantly improved graft function. The present study thus shows the benefits of enhanced protection of the renal vasculature during cold storage, whereby increasing the antithrombotic and anti-adhesive properties of the vascular endothelium yields improved renal function early after transplantation.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Surgery Urology and Nephrology Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-354353 (URN)10.1038/s41598-018-21463-1 (DOI)000428235200024 ()29581529 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 602699VINNOVA
Available from: 2018-08-08 Created: 2018-08-08 Last updated: 2018-08-08Bibliographically approved
Hellström, V., Tufveson, G., Wallgren, A., Loskog, A., Larsson, E., Tötterman, T., . . . Lorant, T. (2017). Donor Derived and BK Virus Positive Urologic Cancers After Renal Transplantation. Paper presented at American Transplant Congress, APR 29-MAY 03, 2017, Chicago, IL. American Journal of Transplantation, 17(S3), 472-472, Article ID A188.
Open this publication in new window or tab >>Donor Derived and BK Virus Positive Urologic Cancers After Renal Transplantation
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2017 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 17, no S3, p. 472-472, article id A188Article in journal, Meeting abstract (Other academic) Published
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-335823 (URN)10.1111/ajt.14306 (DOI)000404515703188 ()
Conference
American Transplant Congress, APR 29-MAY 03, 2017, Chicago, IL
Available from: 2018-01-15 Created: 2018-01-15 Last updated: 2018-01-15Bibliographically approved
Hellström, V., Lorant, T., Döhler, B., Tufveson, G. & Enblad, G. (2017). High posttransplant cancer incidence in renal transplanted patients with pretransplant cancer. Transplantation, 101(6), 1295-1302
Open this publication in new window or tab >>High posttransplant cancer incidence in renal transplanted patients with pretransplant cancer
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2017 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 101, no 6, p. 1295-1302Article in journal (Refereed) Published
Abstract [en]

Background. Patients with previous cancer have increasingly been accepted for renal transplantation. Posttransplant cancer risk and survival rates of these patients are unknown. Our objective was to assess the risk of posttransplant cancer in this patient group. Methods. In this retrospective, nested case-control study, we assessed the outcome of all (n = 95) renal transplanted patients with pretransplant cancer diagnoses in the Uppsala-Orebro region, Sweden. The control group was obtained from the Collaborative Transplant Study registry and included European patients without pretransplant cancer. The other control group comprised the entire renal transplanted population in Uppsala. Development of recurrent cancer, de novo cancer, and patient survival were determined. Results. Patients with pretransplant cancer showed higher incidence of posttransplant cancers and shorter survival compared with the control groups (P < 0.001). No obvious pattern in malignant diagnoses was observed. Death-censored graft survival was unaffected. Conclusions. Despite previously adequate cancer treatments and favorable prognoses, almost half of the patients experienced a posttransplant cancer. These observations do not justify abstaining from transplanting all patients with previous malignancies, because more than 50% of the patients survive 10 years posttransplantation. A careful oncological surveillance pretransplant as well as posttransplant is recommended.

National Category
Medical and Health Sciences
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-282111 (URN)10.1097/TP.0000000000001225 (DOI)000401835800026 ()27163539 (PubMedID)
Available from: 2016-04-02 Created: 2016-04-01 Last updated: 2017-07-04Bibliographically approved
Jordan, S. C., Lorant, T., Choi, J., Kjellman, C., Winstedt, L., Bengtsson, M., . . . Tufveson, G. (2017). IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.. New England Journal of Medicine, 377(5), 442-453
Open this publication in new window or tab >>IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.
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2017 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 5, p. 442-453Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Donor-specific antibodies create an immunologic barrier to transplantation. Current therapies to modify donor-specific antibodies are limited and ineffective in the most highly HLA-sensitized patients. The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization. We report on the combined experience of two independently performed open-label, phase 1-2 trials (conducted in Sweden and the United States) that assessed the efficacy of IdeS with regard to desensitization and transplantation of a kidney from an HLA-incompatible donor.

METHODS: We administered IdeS to 25 highly HLA-sensitized patients (11 patients in Uppsala or Stockholm, Sweden, and 14 in Los Angeles) before the transplantation of a kidney from an HLA-incompatible donor. Frequent monitoring for adverse events, outcomes, donor-specific antibodies, and renal function was performed, as were renal biopsies. Immunosuppression after transplantation consisted of tacrolimus, mycophenolate mofetil, and glucocorticoids. Patients in the U.S. study also received intravenous immune globulin and rituximab after transplantation to prevent antibody rebound.

RESULTS: Recipients in the U.S. study had a significantly longer cold ischemia time (the time elapsed between procurement of the organ and transplantation), a significantly higher rate of delayed graft function, and significantly higher levels of class I donor-specific antibodies than those in the Swedish study. A total of 38 serious adverse events occurred in 15 patients (5 events were adjudicated as being possibly related to IdeS). At transplantation, total IgG and HLA antibodies were eliminated. A total of 24 of 25 patients had perfusion of allografts after transplantation. Antibody-mediated rejection occurred in 10 patients (7 patients in the U.S. study and 3 in the Swedish study) at 2 weeks to 5 months after transplantation; all these patients had a response to treatment. One graft loss, mediated by non-HLA IgM and IgA antibodies, occurred.

CONCLUSIONS: IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients. (Funded by Hansa Medical; ClinicalTrials.gov numbers, NCT02224820 , NCT02426684 , and NCT02475551 .).

Place, publisher, year, edition, pages
Massachusetts Medical Society, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-333282 (URN)10.1056/NEJMoa1612567 (DOI)000406747100006 ()28767349 (PubMedID)
Note

Drs. Jordan and Lorant, and Drs. Vo and Tufveson, contributed equally to this article. 

Available from: 2017-11-09 Created: 2017-11-09 Last updated: 2017-11-23Bibliographically approved
Jordan, S. C., Lorant, T. & Choi, J. (2017). Reply to: IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation [Letter to the editor]. New England Journal of Medicine, 377(17), 1693-1694
Open this publication in new window or tab >>Reply to: IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation
2017 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 17, p. 1693-1694Article in journal, Letter (Other academic) Published
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-346786 (URN)000413691900023 ()
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-03-22Bibliographically approved
Hellström, V., Enström, Y., Enblad, G., Tufveson, G., Renlund, H., Lorant, T. & Nyberg, F. (2017). Risk Factors for De Novo Squamous Cell Carcinoma Development in Renal Transplant Recipients with a Previous Squamous Cell Carcinoma.. Acta Dermato-Venereologica, 97(6), 751-753
Open this publication in new window or tab >>Risk Factors for De Novo Squamous Cell Carcinoma Development in Renal Transplant Recipients with a Previous Squamous Cell Carcinoma.
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2017 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 6, p. 751-753Article in journal, Editorial material (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-333244 (URN)10.2340/00015555-2606 (DOI)000405575100018 ()28093599 (PubMedID)
Available from: 2017-11-09 Created: 2017-11-09 Last updated: 2018-02-16Bibliographically approved
Hellström, V., Enström, Y., von Zur-Mühlen, B., Hagberg, H., Laurell, A., Nyberg, F., . . . Lorant, T. (2016). Malignancies in transplanted patients: Multidisciplinary evaluation and switch to mTOR inhibitors after kidney transplantation - experiences from a prospective, clinical, observational study. Acta Oncologica, 55(6), 774-781
Open this publication in new window or tab >>Malignancies in transplanted patients: Multidisciplinary evaluation and switch to mTOR inhibitors after kidney transplantation - experiences from a prospective, clinical, observational study
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2016 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 6, p. 774-781Article in journal (Refereed) Published
Abstract [en]

Background Solid organ transplant recipients are at increased risk of developing malignancies. The objective of this prospective, observational, one-armed study was to study the feasibility to add a mammalian target of rapamycin (mTOR) inhibitor to the immunosuppressive regimen in transplanted patients with post-transplant malignancies. During the trial the need to improve identification of post-transplant malignancies and to reassure adequate oncological treatment of these patients became evident. Multidisciplinary team (MDT) evaluation of oncological and immunosuppressive treatments was implemented for all patients with malignancies after renal or combined renal and pancreas transplantation because of the trial.Material and methods At Uppsala University Hospital, Sweden, a MDT consisting of transplant surgeons, nephrologists, oncologists and dermatologists evaluated 120 renal or combined renal and pancreas-transplanted recipients diagnosed with malignancies from September 2006 to July 2012. To identify all malignancies, the population was linked to the Regional Tumor Registry (RTR). We recorded to which extent a switch to mTOR inhibitors was possible and how often the originally planned oncological managements were adjusted. All patients were followed for three years. (ClinicalTrials.gov: NCT02241564).Results In 76 of 120 patients (63%) a switch to mTOR inhibitors was possible. Immunosuppression was interrupted in seven patients (6%), reduced in three patients (2%) and remained unchanged in 34 of 120 patients (28%). Identification of post-transplant malignancies increased significantly after linkage to RTR (p=0.015). The initially recommended oncological treatment was adjusted in 23 of 44 patients (52%) with solid or hematological malignancies; 36 of these patients (82%) were treated according to national guidelines.Conclusion In two thirds of the patients the immunosuppressive treatment could be changed to an mTOR inhibitor with anti-tumor effects in transplanted patients with post-transplant malignancies. The use of regional tumor registers considerably improved the identification of patients with post-transplant malignancies indicating that post-transplant malignancies might be timely underreported in transplant registers.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016
Keywords
Malignant tumours, Renal transplantation
National Category
Cancer and Oncology
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-282106 (URN)10.3109/0284186X.2015.1130855 (DOI)000377122300017 ()26824275 (PubMedID)
Available from: 2016-04-02 Created: 2016-04-01 Last updated: 2017-11-30Bibliographically approved
Eich, T., Lorant, T., Eriksson, B.-M., Winstedt, L., Backman, L., Larsson, E., . . . Bengtsson, M. (2016). Rapid Desensitisation Of Anti-Hla Antibodies Using The Igg Degrading Enzyme Ides In Sensitised Patients With Chronic Kidney Disease. HLA, 87(4), 226-227
Open this publication in new window or tab >>Rapid Desensitisation Of Anti-Hla Antibodies Using The Igg Degrading Enzyme Ides In Sensitised Patients With Chronic Kidney Disease
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2016 (English)In: HLA, ISSN 2059-2302, Vol. 87, no 4, p. 226-227Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-308508 (URN)000383951500063 ()
Available from: 2016-11-28 Created: 2016-11-28 Last updated: 2018-01-13Bibliographically approved
Eich, T., Lorant, T., Eriksson, B.-M., Winstedt, L., Bäckman, L., Larsson, E., . . . Bengtsson, M. (2016). Rapid desensitisation of anti-HLA antibodies using the IgG degrading enzyme IdeS in sensitized patients with chronic kidney disease. Paper presented at 30th European Immunogenetics and Histocompatibility Conference (EFI). Tissue Antigens, 87(4), 226-227
Open this publication in new window or tab >>Rapid desensitisation of anti-HLA antibodies using the IgG degrading enzyme IdeS in sensitized patients with chronic kidney disease
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2016 (English)In: Tissue Antigens, ISSN 0001-2815, E-ISSN 1399-0039, Vol. 87, no 4, p. 226-227Article in journal, Meeting abstract (Other academic) Published
Keywords
enzyme, transplantation, immunised
National Category
Medical and Health Sciences
Research subject
Immunology
Identifiers
urn:nbn:se:uu:diva-345105 (URN)
Conference
30th European Immunogenetics and Histocompatibility Conference (EFI)
Available from: 2018-03-08 Created: 2018-03-08 Last updated: 2018-03-08Bibliographically approved
Hellström, V., Lorant, T., Dohler, B., Tufveson, G. & Enblad, G. (2015). Elevated Post-Transplant Cancer Incidence And Reduced Survival In Patients With Pretransplant Tumors. Transplant International, 28, 183-184
Open this publication in new window or tab >>Elevated Post-Transplant Cancer Incidence And Reduced Survival In Patients With Pretransplant Tumors
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2015 (English)In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 28, p. 183-184Article in journal, Meeting abstract (Other academic) Published
National Category
Surgery Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-281008 (URN)000367726701156 ()
Available from: 2016-03-16 Created: 2016-03-16 Last updated: 2017-11-30Bibliographically approved
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