| 1. |
- Bevilacqua, Ruggero, et al.
(författare)
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Challenges in the Management of Kidney Allograft Herniation With a Single-stage Pedicled Anterolateral Thigh Flap
- 2022
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Ingår i: Transplantation direct. - : Wolters Kluwer. - 2373-8731. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Wound complications are the most common surgical complication after kidney allograft transplantation. Total wound rupture exposing the entire kidney is a rare and not well-described event. We present a successful treatment of this complication in a patient admitted to our unit. A single-stage procedure was performed combining debridement and reconstruction with a pedicled anterolateral thigh flap and an iliotibial band transferring. A short literature review is performed comparing the different treatment strategies and results.
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| 2. |
- Bockermann, Robert, et al.
(författare)
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Imlifidase-generated Single-cleaved IgG : Implications for Transplantation
- 2022
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 106:7, s. 1485-1496
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Tidskriftsartikel (refereegranskat)abstract
- Background. Imlifidase is an immunoglobulin G (IgG)-specific protease conditionally approved in the EU for desensitization in highly sensitized crossmatch positive kidney transplant patients. Imlifidase efficiently cleaves both heavy chains of IgG in a 2-step process. However, low levels of the intermediate cleavage product, single-cleaved IgG (scIgG), may persist in the circulation. The study objective was to investigate Fc-mediated effector functions of scIgG and its potential impact on common clinical immunologic assays used to assess transplant eligibility.Methods. Imlifidase-generated scIgG, obtained by in vitro cleavage of HLA-sensitized patient serum or selected antibodies, was investigated in different complement- and Fc gamma R-dependent assays and models, including clinical tests used to evaluate HLA-specific antibodies.Results. ScIgG had significantly reduced Fc-mediated effector function compared with intact IgG, although some degree of activity in complement- and Fc gamma R-dependent models was still detectable. A preparation of concentrated scIgG generated from a highly HLA-sensitized individual gave rise to a positive signal in the anti-HLA IgG LABScreen, which uses anti-Fc detection, but was entirely negative in the C1qScreen. The same high-concentration HLA-binding scIgG preparation also generated positive complement-dependent cytotoxicity responses against 80%-100% of donor T and B cells, although follow-up titrations demonstrated a much lower intrinsic activity than for intact anti-HLA IgG.Conclusions. ScIgG has a significantly reduced capacity to mediate Fc-dependent effector functions. However, remaining HLA-reactive scIgG in plasma after imlifidase treatment can cause positive assay results equivalent to intact IgG in clinical assays. Therefore, complete IgG cleavage after imlifidase treatment is essential to allow correct decision-making in relation to transplant eligibility.
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| 5. |
- Hellström, Vivan, et al.
(författare)
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Donor-derived urologic cancers after renal transplantation : A retrospective non-randomized scientific analysis
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Malignancies in the urinary tract and the kidney graft are quite common after kidney transplantation. In some selected cases tumours develop from donor-derived tissue.OBJECTIVES: We hypothesised that there is a clinical value to investigate donor/recipient origin in urologic malignancies in renal transplant recipients.METHODS: In this retrospective study, including patients transplanted between the years 1969 and 2014 at Uppsala University Hospital, Sweden, 11 patients with malignancies in urinary tract and 4 patients with malignancies in kidney transplants were investigated. Donor/recipient origin of tumour tissue was analysed by polymerase chain reaction (PCR) of human leucocyte antigen (HLA) genotypes or by fluorescence in situ hybridization (FISH analysis) of sex chromosomes. HLA genotype and sex chromosomes of the tumour were compared to the known HLA genotype and sex chromosomes of recipient and donor.RESULTS: Three of ten cancers in the urinary tract and three of four cancers in the kidney transplants were donor-derived.CONCLUSIONS: We suggest that urologic malignancies in renal transplant recipients can be investigated for transplant origin. In addition to conventional therapy the allograft immune response against these tumours can be valuable to treat donor-derived cancers.
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| 6. |
- Hellström, Vivan, et al.
(författare)
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High posttransplant cancer incidence in renal transplanted patients with pretransplant cancer
- 2017
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 101:6, s. 1295-1302
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Hellström, Vivan, et al.
(författare)
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Njurtransplanterade med maligna tumörer en växande patientgrupp : [Kidney transplanted persons with malignant tumors is a growing patient group]
- 2012
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 109:39-40, s. 1766-1769
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of malignant tumors in the organ transplanted population is increased 3-5 fold compared to the general population. The spectrum of tumors is different, the tumor growth is more aggressive and the prognosis is worse. In order to identify patients with post-transplant malignant tumors, the transplant registries in Stockholm, Uppsala and Gothenburg were cross run with the respective regional oncologic registries (ROC). It was found, that despite a generally good follow up, information about more than 50% of the malignant tumors is missing at the transplant centers. According to international guidelines this patient group should be evaluated by multidisciplinary teams consisting of transplant surgeons/nephrologists, oncologists and dermatologists with experience of transplantation to get optimal medical treatment. We would therefore like to emphasize the importance of referring all renal transplanted patients with malignant tumors to the transplant centers for multidisciplinary evaluation of the immunosuppressive as well as oncologic treatment.
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| 8. |
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| 9. |
- Jordan, Stanley C, et al.
(författare)
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IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.
- 2017
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:5, s. 442-453
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Tidskriftsartikel (refereegranskat)abstract
- 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 .).
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