| 1. |
- Christensson, Anders, et al.
(författare)
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Serum cystatin C is a more sensitive and more accurate marker of glomerular filtration rate than enzymatic measurements of creatinine in renal transplantation.
- 2003
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Ingår i: Nephron Physiology. - : S. Karger AG. - 1660-2137. ; 94:2, s. 19-27
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Serum creatinine has several drawbacks as marker of glomerular filtration rate (GFR), and therefore serum cystatin C has been proposed as a more optimal GFR marker. Previous reports have suggested benefits of serum cystatin C measurements in patients with renal transplants. The purpose of the present study was to evaluate the diagnostic accuracy of cystatin C measurements compared with enzymatic creatinine measurements as serum markers of GFR (established from plasma clearance of iohexol) in a large cohort of stable renal transplant recipients and in the early postoperative phase. <i>Methods:</i> Renal transplant patients (n = 125) with stable graft function were evaluated from reciprocals of serum creatinine and cystatin C compared with iohexol clearance. Fourteen patients were examined immediately after the onset of renal function. Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. <i>Results:</i> In stable renal transplant recipients, serum cystatin C showed a significantly (p = 0.033) closer correlation (r = 0.89 or 79% co-variance) with iohexol clearance than did serum creatinine (r = 0.81 or 66% co-variance). Using the χ<sup>2</sup> test and a cut-off at 60 ml/min/1.73 m<sup>2</sup>, serum cystatin C levels demonstrated significantly higher sensitivity for early GFR impairment (p = 0.0045) compared with serum creatinine measurements. On the first day after transplantation, serum cystatin C fell more rapidly than serum creatinine. <i>Conclusion:</i> Serum cystatin C levels correlate significantly closer to accurate measurements of GFR and are significantly more sensitive to detect early GFR impairment than enzymatic measurements of creatinine in serum.
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| 2. |
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| 3. |
- Broecker, Verena, et al.
(författare)
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Uterus transplantation: Histological findings in explants at elective hysterectomy
- 2021
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 21:2, s. 798-808
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Tidskriftsartikel (refereegranskat)abstract
- Uterus transplantation has enabled women with absolute uterine factor infertility to carry a pregnancy. The first human uterus transplantation trial was initiated in 2013 in Gothenburg, Sweden. It was completed with 7 transplantations with long-term allograft survival and 9 children born from 6 women. In the present study we describe the histopathology of these 7 allografts, which were removed at 22-83 months after transplantation, and compare findings to control cases. Morphological findings in a subset of explants included linear subepithelial inflammation and perivascular stromal inflammation in the cervix, small inflammatory foci in the myometrium, and intimal inflammation in larger arteries. The average number of T cells, B cells, and macrophages was higher in transplants compared to normal controls, but variability was high among transplants. Chronic-active vascular rejection was seen in 2 of 7 transplants, both showed also inflammation in the cervix. Further, the inflammation seen in the cervix reflected the inflammation in the myometrium, suggesting that cervical biopsies are suitable to monitor rejection. However, the degree of inflammation and signs of rejection in explants did not reflect on the possibility to become pregnant in this limited series.
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| 4. |
- Brännström, Mats, 1958, et al.
(författare)
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Live birth after robotic-assisted live donor uterus transplantation.
- 2020
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 99:9, s. 1222-1229
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Tidskriftsartikel (refereegranskat)abstract
- The proof-of-concept of uterus transplantation, as a treatment for absolute uterine factor infertility, came with the first live birth after uterus transplantation, which took place in Sweden in 2014. This was after a live donor procedure, with laparotomy in both donor and recipient. In our second, ongoing trial we introduced a robotic-assisted laparoscopic surgery of the donor to develop minimal invasive surgery for this procedure. Here, we report the surgery and pregnancy behind the first live birth from that trial.In the present study, within a prospective observational study, a 62-year-old mother was the uterus donor and her 33-year-old daughter with uterine absence as part of the Mayer-Rokitansky-Küster-Hauser syndrome, was the recipient. Donor surgery was mainly done by robotic-assisted laparoscopy, involving dissections of the utero-vaginal fossa, arteries and ureters. The last part of surgery was by laparotomy. Recipient laparotomy included vascular anastomoses to the external iliac vessels. Data relating to in vitro fertilization, surgery, follow up, obstetrics and postnatal growth are presented.Three in vitro fertilization cycles prior to transplantation gave 12 cryopreserved embryos. The surgical time of the donor in the robot was 360minutes, according to protocol. The durations for robotic surgery for dissections of the utero-vaginal fossa, arteries and ureters were 30, 160 and 84minutes, respectively. The remainder of donor surgery was by laparotomy. Recipient surgery included preparations of the vaginal vault, three end-to-side anastomoses (one arterial, two venous) on each side to the external iliacs and fixation of the uterus. Ten months after transplantation, one blastocyst was transferred and resulted in pregnancy, which proceeded uneventfully until elective cesarean section in week 36+1 . A healthy boy (Apgar 9-10-10) was delivered. Follow up of child has been uneventful for 12months.This is the first report of a live birth after use of robotic-assisted laparoscopy in uterus transplantation and is thereby a proof-of-concept of use of minimal invasive surgery in this new type of transplantation.
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| 5. |
- Brännström, Mats, 1958, et al.
(författare)
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Livebirth after uterus transplantation.
- 2015
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Ingår i: Lancet. - 1474-547X. ; 385:9968, s. 607-616
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Tidskriftsartikel (refereegranskat)abstract
- Uterus transplantation is the first available treatment for absolute uterine infertility, which is caused by absence of the uterus or the presence of a non-functional uterus. Eleven human uterus transplantation attempts have been done worldwide but no livebirth has yet been reported.
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| 6. |
- Brännström, Mats, 1958, et al.
(författare)
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One uterus bridging three generations: first live birth after mother-to-daughter uterus transplantation
- 2016
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 106:2, s. 261-266
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether a uterus from the mother of a woman with absolute uterine factor infertility can be transplanted to daughter and carry a pregnancy with delivery of a healthy child. Patient(s): Twenty eight-year-old woman with uterine agenesis, her male partner, and her 50-year-old mother. Intervention(s): In vitro fertilization with embryo cryopreservation before live donor uterus transplantation (UTx). Induction immunosuppression. Embryo transfer 12 months after UTx, pregnancy controls, delivery, and hysterectomy. Main Outcome Measure(s): Results of IVF-ET, parameters of pregnancy/birth, and surgical data of transplantation/cesarean section/hysterectomy. Result(s): Two IVF cycles before UTx resulted in 10 cryopreserved embryos. Donor surgery included hysterectomy with vascular pedicles of uterine vessels and proximal vessels up to and including parts of internal iliacs. Recipient surgery was by bilateral vascular connections to external iliacs, vaginal-vaginal anastomosis, and uterine fixation. Pregnancy occurred at the first single ET, and the pregnancy proceeded uneventfully until gestational week 34, when the patient developed cholestasis with intense pruritus. Cesarean section was performed at 34+6, with delivery of a healthy boy (weight 2,335 g). Hysterectomy was performed 3.5 months after delivery. The weight of the healthy child at 12 months was 9.3 kg. Grandmother (uterus donor) and mother are in good health 3 years after UTx. Conclusion(s): This is the first report of a live birth after mother-to-daughter UTx, and it also represents the second birth ever after human UTx. (C) 2016 by American Society for Reproductive Medicine.
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| 7. |
- Brännström, Mats, 1958, et al.
(författare)
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Outcome of Recipient Surgery and 6-Month Follow-Up of the Swedish Live Donor Robotic Uterus Transplantation Trial.
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Uterus transplantation has proved to be a feasible treatment for uterine factor infertility. Herein, we report on recipient outcome in the robotic uterus transplantation trial of 2017-2019. The eight recipients had congenital uterine aplasia. The donors were six mothers, one sister, and one family friend. Donor surgery was by robotic-assisted laparoscopy. Recipient surgery was by laparotomy and vascular anastomoses to the external iliacs. The duration (median (ranges)) of recipient surgery, blood loss, measured (left/right) uterine artery blood flow after reperfusion, and length of hospital stay were 5.15 h (4.5-6.6), 300 mL (150-600), 43.5 mL/min (20-125)/37.5 mL/min (10-98), and 6 days (5-9), respectively. Postoperative uterine perfusion evaluated by color Doppler showed open anastomoses but restricted blood distribution in two cases. Repeated cervical biopsies in these two cases initially showed ischemia and, later, necrosis. Endometrial growth was not seen, and hysterectomy was later performed, with pathology showing partly viable myometrium and fibrosis but necrosis towards the cavity. The other six patients acquired regular menstrual cyclicity. Surgery was performed in two patients to correct vaginal stenosis. Reversible rejection episodes were seen in two patients. In conclusion, the rate of viable uterine grafts during the initial 6-months of the present study (75%) leaves room for improvement in the inclusion/exclusion criteria of donors and in surgical techniques. Initial low blood flow may indicate subsequent graft failure.
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| 8. |
- Davidson, Thomas, et al.
(författare)
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The costs of human uterus transplantation: a study based on the nine cases of the initial Swedish live donor trial
- 2021
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 36:2, s. 358-366
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: What are the costs of live donor uterus transplantation in a European setting? SUMMARY ANSWER: The total costs for preoperative investigations, including IVF, and live donor uterus transplantation including postoperative costs for 2 months, were calculated to be (sic) 74 564 (mean), with the costs of recipient being somewhat higher than for donor and the cost components of total costs distributed between sick leave (25.7%), postoperative hospitalization (17.8%), surgery (17.1%), preoperative investigations (15.7%), anaesthesia (9.7%), drugs (7.8%), tests after surgery (4.0%) and for re-hospitalization (2.2%). WHAT IS KNOWN ALREADY: Uterus transplantation has proved to be successful by demonstrations of live births, both after live donor and deceased donor procedures. The transplantation is considered as a complex and expensive infertility treatment. There exist no analyses of costs involved in uterus transplantation. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included nine uterus transplantations procedures, performed in Sweden in 2013. Study duration of this health economic study included 6-12 months of pre-transplantation investigations and the time interval from transplantation to 2 months after. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine triads of uterus recipient, partner of recipient and uterus donor participated. All prospective recipients were in stable relationships and performed IVF with their partners before transplantation. The nine donors were relatives or family friends. The recipients and donors underwent pre-transplantation investigations with imaging, laboratory tests and psychological/medical screening prior to transplantation. Transplantation was by laparotomy in both donor and recipient. Standard immunosuppression and postoperative medication were used. After discharge from the hospital, the recipients were followed frequently with laboratory tests and examinations. MAIN RESULTS AND THE ROLE OF CHANCE: The mean costs for preoperative investigations, including IVF, and live donor uterus transplantation with postoperative costs for 2 months, were calculated to be (sic)74 564 (range (sic) 50 960-(sic)99 658), from a societal perspective. The four largest components were cost of sick leave (sic) 19 164), cost of postoperative hospitalization (sic)13 246), surgery cost (sic)12 779) and costs for preoperative investigations, including IVF (sic) 11 739). Smaller components were costs for anaesthesia (sic) 7207), costs for drugs (sic) 5821), costs for post-surgical tests (sic) 2985) and costs for re-hospitalization (sic)1623). The costs of the recipient (sic) 42 984) were somewhat higher than the costs of the donor (sic) 31 580), but in terms of costs, they should be viewed as one entity. By using a health care perspective, excluding cost for productivity loss, the total costs would be reduced by 26%. LIMITATIONS, REASONS FOR CAUTION: A limitation is the restricted sample size and that this is in the experimental, clinical stage of development. WIDER IMPLICATIONS OF THE FINDINGS: The results provide the first information concerning the costs for pre-transplantation investigations and uterus transplantation procedures with postoperative follow-up. We consider the total estimate to be in the higher interval, because of the extensive research protocol. It is likely that the cost of live donor uterus transplantation will vary between countries and that the costs will be lower in a future clinical setting.
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| 9. |
- Ekberg, Henrik, et al.
(författare)
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Cyclosporine, tacrolimus and sirolimus retain their distinct toxicity profiles despite low doses in the Symphony study.
- 2010
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 25, s. 2004-2010
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Reducing side effects of immunosuppressive regimens has become a priority in transplantation medicine because of the large number of patients and grafts that succumb to infection in the short term and cardiovascular disease in the long term. The Symphony study was a 12-month prospective, randomized, open-label, multi-centre, four parallel arm study that aimed to evaluate the safety and efficacy of low-dose immunosuppressive regimens compared with a standard-dose regimen in renal transplant recipients. This sub-analysis focuses on specific toxicities observed with the low-dose regimens. METHODS: Adult patients (n = 1645) scheduled to undergo renal transplantation received low-dose cyclosporine (CsA), tacrolimus (Tac) or sirolimus (SRL) in addition to daclizumab induction or standard-dose cyclosporine without induction. All patients received mycophenolate mofetil and corticosteroids. We evaluated the incidence of adverse events (AEs), tested specific group differences and assessed the relationship of selected AEs with drug levels. RESULTS: The four arms had similar incidences of AEs, but serious AEs were more common with low-dose SRL and led to more discontinuations. Infections were the most common AEs, with the highest incidence in the standard-dose CsA group, in particular, cytomegalovirus (CMV) infections. Low-dose Tac had the most reports of new-onset diabetes, leucopenia and diarrhoea. Low-dose SRL negatively influenced triglycerides, wound healing, lymphocele and anaemia. We found only weak relationships between specific AEs and drug levels. CONCLUSIONS: Despite the low doses, CsA, Tac and SRL retained distinct and different toxicity profiles. These findings may be of relevance for tailoring specific immunosuppressive regimens to patients with particular needs.
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| 10. |
- Ekberg, Jana, 1964, et al.
(författare)
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A Randomized Controlled Trial on Safety of Steroid Avoidance in Immunologically Low-Risk Kidney Transplant Recipients
- 2022
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 7:2, s. 259-269
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Steroid-based immunosuppression after transplantation increases the risk of post-transplant diabetes mellitus (PTDM), with adverse effects on patient and graft survival. In the SAILOR study, we investigated the safety and efficacy of complete steroid avoidance in immunologically low-risk kidney recipients without diabetes on the current standard-of-care maintenance regimen with tacrolimus/mycophenolate mofetil (MMF). Methods: In this 2-year, multicenter, open-label trial, a total of 222 patients were randomized to receive either steroid avoidance protocol (tacrolimus/MMF/antithymocyte globulin [ATG] induction [n = 113]) or steroid maintenance protocol (tacrolimus/MMF/prednisolone/basiliximab-induction [n = 109]). Results: At 1 year, no significant differences were found between steroid avoidance and steroid maintenance arms in the incidence of PTDM, the primary end point (12.4% vs. 18.3%, respectively, P = 0.30, CI: 16.3–4.4), or in overall biopsy-proven rejections (15% vs. 13.8%, respectively, P = 0.85). At 2 years, the composite end point of freedom from acute rejection, graft loss, and death (81% vs. 85%, respectively, P = 0.4), kidney function, or adverse events was comparable between the 2 arms. Moreover, 63.9% of the patients in the steroid avoidance arm remained free from steroids at 2 years. Conclusion: The SAILOR study provides further evidence for the feasibility, safety, and efficacy of early steroid-free treatment at 2 years in immunologically low-risk kidney recipients with tacrolimus/MMF maintenance regimen. © 2021 International Society of Nephrology
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