| 1. |
- Norén, Åsa, et al.
(author)
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End-ischemic hypothermic oxygenated machine perfusion does not improve renal outcome following liver transplantation from aged donors: A single-center retrospective report
- 2023
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In: ARTIFICIAL ORGANS. - 0160-564X .- 1525-1594. ; 47:12, s. 1854-1864
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Journal article (peer-reviewed)abstract
- Background: Organ transplantation using grafts from elderly donors entails a higher risk for severe ischemia-reperfusion injury (IRI). Advanced IRI after liver transplantation (LT) seems to be associated with the development of acute kidney injury (AKI). We studied if end-ischemic hypothermic oxygenated machine perfusion (HOPE) of liver grafts, aimed at mitigating liver IRI, impacts on the frequency and severity of AKI after LT. Methods: LTs performed at our center between January 2017 and December 2022 using organs from deceased brain-dead donors aged 70 or older were reviewed. From November 2020 on, HOPE was performed routinely in this donor category. The frequency and severity of AKI (KDIGO criteria) within 48 hours of graft reperfusion and the model of early allograft function (MEAF) were compared between HOPE-LTs (n = 30) and control LTs (n = 71). Results: AKI developed in 23/30 (77%) HOPE-LTs and in 40/71 (56%) control LTs (p = n.s.), with no difference in severity and timing between groups. Renal replacement therapy was required in 3/30 (10%) HOPE-LTs and 6/71 (8%) control LTs. In addition, transaminase leak during the first week (marker of IRI) and MEAF were similar between groups. These findings persisted after propensity matching. Histology showed more hepatocyte vacuolization and higher Suzuki score in HOPE-LTs. Although this analysis could have been underpowered, no trends supporting the benefit of HOPE on liver and renal injury after LT were ever identified. Conclusions: In conclusion, HOPE in this group of older donors does not seem to improve either graft IRI, or the incidence of early AKI after LT.
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| 2. |
- Abele, Dace, et al.
(author)
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Including the liver in the visceral allograft: Impact on donor-specific anti-HLA antibodies and long-term outcomes
- 2024
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In: HUMAN IMMUNOLOGY. - 0198-8859 .- 1879-1166. ; 85:2
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Journal article (peer-reviewed)abstract
- Humoral immunity emerges as a risk factor for graft failure after visceral transplantation (VTx) and development of donor-specific anti-HLA antibodies (DSAs) has been linked with poor outcomes. In most cases, a simultaneous liver transplant can be safely performed in sensitized patients with DSA and appears protective against lymphocytotoxic antibodies. We investigated the incidence of acute (AR) and chronic rejection (CR) in 32 VTx without any B cell-depleting pre-treatment (6 isolated intestinal transplants (IT) and 26 liver-containing, multivisceral transplants (MVT) and assessed the presence of donor-specific antibodies (DSA) pre- and posttransplantation. Twenty-one patients (65 %) developed AR, 15 (57 %) of the MVT and 6 (100 %) of the IT (p = 0.05). CR occurred in 4 IT (60 %, p < 0.001). At one month, de novo DSA were present in 71 % of VTx (66 % MVT vs 100 % IT, p = 0.09). At the last available follow-up, 69 % of the MVT and 50 % of the IT patients were DSA-free. De novo DSA seemed more persistent (7/19, 37 %) than pre-Tx DSA (1/6, 17 %; p = n.s.), de novo DSA were more frequently specific for HLA class II than class I, 16/19 (84 %) vs. 7/19 (37 %; p = 0.003), and HLA-DQ was their most frequent target HLA. DQ mismatches appeared to be a risk factor for developing de novo DSA. In conclusion, liver-containing visceral allografts have superior shortand long-term outcomes compared with liver-free allografts. De novo DSA develop early and frequently after VTx performed without B cell-depleting induction therapy, but the exact role of DSA in the pathogenesis of rejection remains unclear.
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| 3. |
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| 4. |
- Campistol, Josep M, et al.
(author)
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Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation.
- 2009
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In: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277. ; 22:7, s. 681-7
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Journal article (peer-reviewed)abstract
- m-TOR inhibitors (e.g. sirolimus) are well-tolerated immunosuppressants used in renal transplantation for prophylaxis of organ rejection, and are associated with long-term graft survival. Early use of sirolimus is often advocated by clinicians, but this may be associated with a number of side-effects including impaired wound-healing, lymphoceles and delayed graft function. As transplant clinicians with experience in the use of sirolimus, we believe such side-effects can be limited by tailored clinical management. We present recommendations based on published literature and our clinical experience. Furthermore, guidance is provided on sirolimus use during surgery, both at transplantation and for subsequent operations.
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| 5. |
- Cederborg, Anna, 1976, et al.
(author)
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Renal function after liver transplantation: Real-world experience with basiliximab induction and delayed reduced-dose tacrolimus
- 2022
-
In: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658. ; 54:8, s. 1076-1083
-
Journal article (peer-reviewed)abstract
- Background: Routine use of delayed reduced-dose calcineurin-inhibitor treatment with induction immunosuppression in liver transplantation to minimize post-operative kidney injury is still scarce. Aim: To evaluate real-world experience of basiliximab induction with delayed reduced-dose tacrolimus. Methods: In a retrospective cohort study, kidney function was evaluated pre- and postoperatively by measured glomerular filtration rate (mGFR). Adult patients undergoing liver transplantation between 2000 and 2017 were divided into a conventional treatment group (immediate-introduction of tacrolimus, target trough levels 10–15 ng/mL, and corticosteroids, n = 203) and a revised treatment group (basiliximab induction, reduced-dose tacrolimus, target through levels 5–8 ng/mL, delayed until day three, and mycophenolate mofetil 2000 mg/day, n = 343). Results: Mean mGFR was similar between groups at wait-listing (85.3 vs 84.1 ml/min/1.73m², p = 0.60), but higher in the revised treatment group at 3 (56.8 vs 63.4 ml/min/1.73m², p = 0.004) and 12 months post-transplant (60.9 vs 69.7 ml/min/1.73m², p<0.001); this difference remained after correcting for multiple confounders and was independent of pre-transplant mGFR. In the revised treatment group, biopsy proven acute rejection rate was lower (38% vs. 21%, p<0.001), and graft-survival better (p = 0.01). Conclusion: Basiliximab induction with delayed reduced-dose tacrolimus is associated with less kidney injury when compared to standard-dose tacrolimus, without increased risk of rejection, graft loss or death. © 2021
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| 6. |
- Chougule, Priti, et al.
(author)
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Isolation and characterization of human primary enterocytes from small intestine using a novel method.
- 2012
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In: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 47:11, s. 1334-43
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Journal article (peer-reviewed)abstract
- Abstract Cell culture studies of enterocytes are important in many fields. However, there are difficulties in obtaining cell lines from adult human intestine, such as microbial contamination of cultures from the tissue samples, short life span of enterocytes, overgrowth of mesenchymal cells, etc. Various model used to obtain adult intestinal cell lines are very complex requiring use of feeder layer or gel matrices. The aim of this study was to establish a novel method for the simple and reproducible isolation of human enterocytes. Enterocytes were isolated from SI samples (n = 5) obtained from cadaveric donors using a mechanical procedure, and separation with immunomagnetic beads coated with anti-EpCAM antibodies. Light and electron microscopy, flow cytometry and immunocytochemistry techniques were used to characterize the isolated cells. Immunohistochemical staining of normal SB biopsies confirmed that the cell cultures maintained an in vivo phenotype as reflected in cytokeratin expression CK18, CK20 and expression of intestine-specific markers such as sucrase isomaltase and maltase glucoamylase. Furthermore, the cells strongly expressed TLR-5, 6, 7, 8 and 10 and several molecules such as CD40, CD86, CD44, ICAM-1 and HLA-DR which are important in triggering cell-mediated immune responses. This novel technique provides a unique in vitro system to study the biology of enterocytes in normal conditions as well as to study inflammatory processes in various small bowel disorders.
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| 7. |
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| 8. |
- Dahlgren, Ulrika Skogsberg, et al.
(author)
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Excellent outcome following emergency deceased donor ABO-incompatible liver transplantation using rituximab and antigen specific immunoadsorption
- 2022
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 57:1, s. 50-59
-
Journal article (peer-reviewed)abstract
- Background The acceptance of ABO-incompatible (ABOi) liver grafts will expand the donor pool for a patient in urgent need for a liver transplantation (LT). Here we report our results with emergency ABOi DD (deceased donor) LT using rituximab and antigen specific immunoadsorption. Patients and Methods 2009 to 2019 we performed 20 ABOi DD LTs (adults n = 17, children n = 3) for patients in urgent need for a LT. Immunosuppression consisted of rituximab (n = 20) and basiliximab (n = 15) or anti-thymocyte globuline (n = 4), intravenous immunoglobulin (IVIG; n = 6), tacrolimus, prednisolone and mycophenolate mofetil. Fifteen patients were treated with IA (n = 14) or both IA and plasmapheresis (PP; n = 1) pre-transplant and 18 patients were treated with IA (n = 15) or both IA and PP (n = 3) post-transplant. The median pre-transplant MELD- score was 40 (range 18-40). Patient and graft survival and complications were compared to a 1:4 case matched control group of ABO-identical or compatible (ABOid/c) DDLT. Results The 1-, 3- and 5-year patient and graft survival rates were 85, 85 and 78% for the ABOi recipients and not significantly different compared to ABOid/c controls. Only one ABOi patient developed antibody-mediated rejection. Conclusion Patient and graft survival after emergency ABOi DDLT using rituximab and immunoadorption was equal to ABOid/DDLT. ABOi DD LT was a successful approach to expand the donor pool for patients in urgent need for a liver graft.
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| 9. |
- Ekberg, Jana, 1964, et al.
(author)
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Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort
- 2023
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In: TRANSPLANTATION DIRECT. - 2373-8731. ; 9:10
-
Journal article (peer-reviewed)abstract
- Background.Chronic kidney disease is common after non-renal solid organ transplantation, mainly secondary to calcineurin inhibitors toxicity. Uterus transplantation (UTx) is an innovative treatment for women with absolute uterine factor infertility. UTx is exclusive because it is transient with the absence of lifelong immunosuppression and is performed in young healthy participants. Therefore, UTx provides a unique setting for evaluating the effect of time-limited calcineurin inhibitors treatment on recipients' kidney function.Methods.In the first UTx cohort worldwide, we studied kidney function using estimated glomerular filtration rate (eGFR) in 7 women over a median follow-up of 121 (119-126) mo.Results.Median eGFR (mL/min/1.73 m2) of the cohort was 113 at UTx, which declined to 74 during month 3, 71 at months 10-12, 76 at hysterectomy (HE), and 83 at last follow-up. Median duration of tacrolimus exposure was 52 (22-83) mo, and median trough levels (mu g/L) were 10 during month 3 and 5.8 at HE. Between UTx and month 3, decline in kidney function was observed in all 7 participants with a median eGFR slope for the whole cohort of -24 mL/min/1.73 m2, which declined further by -4 mL/min/1.73 m2 until months 10-12. Thereafter, eGFR slope improved in 3 participants, remained stable in 3, and worsened in 1 until HE/tacrolimus discontinuation, after which it improved in 2. Eventually, between UTx and last follow-up, 4 of 7 participants had a decline in their eGFR, the median annual eGFR slope being negative at -1.9 mL/min/1.73 m2/y for the whole group.Conclusions.Kidney function declined in all recipients early after UTx followed by a persistent long-term decrease in majority, despite transplantectomy and discontinuation of immunosuppression. Thus, UTx may incur an increased risk of chronic kidney disease even in this young and healthy population, highlighting the importance of close surveillance of kidney function and minimization of tacrolimus exposure.
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| 10. |
- Fistouris, Johan, et al.
(author)
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Pseudoaneurysm of the hepatic artery following liver transplantation
- 2006
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In: Transplantation proceedings. - 0041-1345. ; 38:8, s. 2679-82
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Journal article (peer-reviewed)abstract
- We report 12 cases of pseudoaneurysm hepatic artery (PA) among 825 liver transplantations (OLT) performed between January 1985 and December 2005. In the early period (1985 to 1995), the incidence was 2.6% and in the later period (1996 to 2005), 0.9%. Median time to onset was 39.5 days post-OLT (range 14 days to 5 years). Six patients presented with rupture into the peritoneum (n = 4) or gastrointestinal tract (n = 2), while five patients presented with gastrointestinal bleed due arteriobiliary fistulation with hemobilia. The twelfth PA was found incidentally during retransplantation. PAs were detected with radiological imaging (n = 4), exploratory laparotomy (n = 6), at autopsy (n = 1) or at retransplantation (n = 1). We performed immediate revascularization, after surgical excision was performed in three and endovascular embolization in one patient. In six patients hepatic artery ligation without revascularization was inevitable with subsequent successful retransplantation in four patients. No PA-specific treatment was attempted in two cases due to the poor prognosis or diagnostic ambiguity. In 10 cases microbial pathogens were cultured in the blood, subhepatic abscesses, or from the wall of the hepatic artery. A hepaticojejunostomy was performed for biliary reconstruction in six patients and two had a hepaticojejunostomy conversion due to biliary leak. Survival in the early period (1985 to 1995) was 14%, whereas during the later period (1996 to 2005), the survival increased to 100% with a 4.2-year median follow-up (range 7.4 months to 6.9 years). Infrequently PA complicates OLT, becoming evident primarily after rupture with hemoperitoneum or a gastrointestinal bleed. Early recognition with angiography is important but acute hemorrhage often requires immediate exploration with ligation of the PA, although surgical or endovascular exclusion of the PA followed by revascularization provides a feasible treatment option.
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| 11. |
- Gustafsson, Bengt I., 1955, et al.
(author)
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Retransplantation of the liver.
- 2006
-
In: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 38:5, s. 1438-9
-
Journal article (peer-reviewed)abstract
- Retransplantation (re-TX) is the only available therapy for irreversible liver graft dysfunction. The outcome of a second procedure depends upon several factors, some of which are not defined at the time of the decision to retransplant. This study is an analysis of all re-TX of the liver performed at our unit between January 1995 and January 2004. Among the 474 liver TX were 55 (11.6%) re-TX in 47 patients. We studied (1) diagnosis at first TX; (2) indication for re-TX and time lapse; (3) donor age and cold ischemia time (CIT); (4) duration of operation, peroperative bleeding, and complications; (5) ICU and ward periods; and (6) patient and graft survivals. Patients who underwent re-TX did not differ from those transplanted once with regard to age, gender, or diagnosis. The indications for re-TX were roughly one-third biliary tract complications/chronic rejection, one-third hepatic artery thrombosis, and one-third others, including primary nonfunction, acute rejection, portal vein thrombosis, sepsis, and B/C hepatitis. The re-TX were "urgent" in 29 and "elective" in 26 cases. Complications were common; about half of the patients were reoperated due to bleeding or biliary problems. To date (May 2004), 15 patients have died (12 "urgent" and 3 "elective"), of whom 5 had well functioning grafts. In summary, liver re-TX is a complicated procedure associated with significant mortality and morbidity, but considering that the actual patient group has a poor prognosis without re-TX, the results are nevertheless encouraging.
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| 12. |
- Herlenius, Gustaf, 1961, et al.
(author)
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Chronic kidney disease - a common and serious complication after intestinal transplantation
- 2008
-
In: Transplantation. - 0041-1337. ; 86:1, s. 108-113
-
Journal article (peer-reviewed)abstract
- Background. Chronic kidney disease after organ transplantation is a serious complication that negatively impacts on long-term patient survival. We describe long-term renal function after intestinal transplantation by serial measurements of glomerular filtration rates (GFR) with 51Chromium EDTA clearance. Materials and Methods. Ten patients with at least 6 months survival form the basis of this report. Glomerular filtration rate measurements were performed at baseline, 3 months posttransplantation, and yearly thereafter. Median follow-up time for the cohort was 1.5 years (0.5–7.8 years). Tacrolimus (Prograf) was discontinued in four patients because of impaired renal function. These four patients were switched to sirolimus (Rapamune) at 11, 18, 24, and 40 months posttransplantation. Results. Median baseline GFR was 67 (22–114) mL/min/1.73 m2. In the adult patients, GFR 3 months posttransplantation had decreased to 50% of the baseline. At 1 year, median GFR in the adult patients was reduced by 72% (n=5). Two patients developed renal failure within the first year and required hemodialysis. One of the pediatric patients fully recovered her renal function, the second pediatric patient lost 20% of her baseline GFR at 6 months posttransplantation. Glomerular filtration rate calculated with the modified diet in renal disease formula consistently overestimated GFR by approximately 30% compared with measured GFR. Conclusion. Chronic kidney disease and renal failure are common after intestinal transplantation. These two factors significantly contribute to poor long-term survival rates. Measurements of GFR may help to identify those individuals at risk for developing chronic kidney disease to implement renal sparing strategies.
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| 13. |
- Herlenius, Gustaf, 1961, et al.
(author)
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Conversion From Calcineurin Inhibitor to Either Mycophenolate Mofetil or Sirolimus Improves Renal Function in Liver Transplant Recipients With Chronic Kidney Disease : Results of a Prospective Randomized Trial
- 2010
-
In: Transplantation Proceedings. - : Elsevier BV. - 0041-1345 .- 1873-2623. ; 42:10, s. 4441-4448
-
Journal article (peer-reviewed)abstract
- Background. Chronic kidney disease (CKD) has emerged as a significant cause of morbidity and a risk factor for mortality after orthotopic liver transplantation (OLT). The use of calcineurin inhibitor (CNI)-based immunosuppression is an important etiologic factor for developing CKD. CNI discontinuation or minimization protocols with replacement of the CNI with non-nephrotoxic drugs, such as mycophenolate mofetil (MMF) or sirolimus (SRL), may have the potential to preserve or recover renal function. Patients and Methods. In this prospective, randomized, single-center study with CNI discontinuation, OLT recipients with CKD (measured glomerular filtration rate [GFRm] 15-45 mL/min/1.73 m(2)) were randomized to either SRL or MMF-based immunosuppression. The main objective was to study the effect of CNI discontinuation on renal function. Secondary aims were to assess the frequency of biopsy-proven acute rejection episodes (BPAR) and adverse events (AE). Renal function was followed with GFRm using 51-Chromium EDTA clearance at baseline, 3 months, and 1 year. Patients were stratified according to baseline GFRm > versus <30 mL/min/1.73 m(2). The 25 patients were enrolled for MMF (n = 13) or SRL (n = 12). The median age at inclusion was 59 years (range, 25-66) and the median number of years after OLT was 4.4 (range, 1-13). Twenty-two patients were followed up for a year; MMF (n = 12) and SRL (n = 10). Results. Mean GFRm for the whole cohort (n = 25) was 31+/-8 mL/min/1.73 m(2) at baseline. After 3 months the GFRm (n = 23) increased to 40+/-10 mL/min/1.73 m(2) (P = .0001) and at 1 year 42 +/- 11 mL/min/1.73 m(2) (n = 22). There was not significant difference between the MMF and the SRL study arms. The cohort (n = 8) with baseline GFRm <30 mL showed a 63% (P = .003) increased filtration after 1 year. There was no significant difference in the frequency or severity of AE between the study arms with the exception of oral ulcerations and persistent hypertriglyceridemia in the SRL group. Two deaths occurred, 1 in each study arm, both probably unrelated to the change in immunosuppression. There were no BPAR episodes. Conclusion. CNI discontinuation and replacement with either MMF or SRL resulted in a significant improvement in renal function even in those patients with severe CKD. The protocol was effective with no acute rejection episodes. The SRL arm showed a higher frequency of oral apthous ulcerations and hypertriglyceridemia. Future studies addressing long-term renal function after CNI discontinuation are needed.
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| 14. |
- Herlenius, Gustaf, 1961, et al.
(author)
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Early renal function post-liver transplantation is predictive of progressive chronic kidney disease.
- 2008
-
In: Scandinavian journal of gastroenterology. - 0036-5521. ; 43:3, s. 344-9
-
Journal article (peer-reviewed)abstract
- With improvements in long-term results after liver transplantation, chronic kidney disease (CKD) has become a highly relevant problem. The early measurement of the glomerular filtration rate (GFR) can identify those patients who are at risk of developing CKD years after liver transplantation. The aims of this study were to describe the prevalence of CKD 5 years after liver transplantation, to study the correlation between measured GFR early after transplantation and late renal function and to identify patients at risk of developing late CKD after liver transplantation.
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| 15. |
- Herlenius, Gustaf, 1961, et al.
(author)
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[Intestinal transplantation--an experimental therapy which has become a realistic alternative]
- 2004
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In: Lakartidningen. - 0023-7205. ; 101:38, s. 2874-8
-
Journal article (peer-reviewed)abstract
- Outcome after intestinal transplantation has improved dramatically since the introduction of novel immunosuppressive agents and refined surgical techniques. Small bowel transplantation is now considered to be the best treatment modality for patients with life threatening complications of intestinal failure and parenteral nutrition. We hereby review the international experience as well as the first ten cases of intestinal transplantation performed in Sweden.
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| 16. |
- Herlenius, Gustaf, 1961
(author)
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Renal function after transplantation of the liver and intestine
- 2010
-
Doctoral thesis (other academic/artistic)abstract
- Background: Chronic kidney disease (CKD) after liver (LT) or intestinal (IT) transplantation may decrease patient survival. Calcineurin inhibitors (CNI) play a major role in its development. Aims: Describe long term renal function and risk factors for developing CKD in adults and children after LT and IT. Investigate if CNI discontinuation in adults after LT improves renal function. Methods: GFR was measured (GFRm) with either Iohexol or 51-Cr EDTA-clearance in both adults and children at different intervals before and after LT and IT. Results: After LT in adults (I), GFRm decreased with 42% after10 years. Prevalence of CKD increased over time: 12% at 5 years and 29% at 10 years. Eight patients (5%) required renal replacement therapy (RRT). Baseline GFRm correlated poorly with late renal function. GFRm at 3 months post-LT correlated well with GFRm at 5 years and GFRm below30 ml/min/1.73m2 at 3 months was a risk factor for CKD at 5 years. After IT (II) CKD was almost universal. RRT was required in 20% of the patients. Calculated GFR (MDRD equation) overestimated GFRm with 30-40%. Children undergoing LT (III) stabilized their renal function after an initial decline. None required RRT. Age above 2 years at LT, hepatic malignancies or metabolic liver diseases as the cause for LT were risk factors for developing CKD. A CNI discontinuation protocol (IV) in 25 adult patients with severe CKD was used with either MMF (n=13) or SRL (n=12). Baseline GFRm (n=25) was 31+/-8 ml/min/1.73m2. At 3 months GFRm (n=23) increased to 40+/-10 ml/min/1.73m2 (p=0.0001). There was no significant difference when comparing the MMF and the SRL study arms. Patients (n=8) with baseline GFRm below 30 ml (CKD stage IV) increased GFRm at one year with 63% (p=0.003). Patients in the SRL group presented a higher incidence of oral ulcerations and hypertriglyceridemia. Two deaths were reported both probably unrelated to the change in immunosuppression. No biopsy proven rejection episodes occurred. Conclusion: CKD is a frequent complication after LT and IT. Early renal function may identify patients at risk of developing CKD. CNI discontinuation under the protection of either MMF or SRL was safe and GFRm increased significantly under the observational period. Keywords: adult liver transplantation, pediatric liver transplantation, intestinal transplantation, multivisceral transplantion, immunosuppression, calcineurin inhibitors, glomerular filtration rate, renal function, nephrotoxicity, chronic kidney disease, renal replacement therapy, mortality ISBN 978-91-628-7981-5 http://hdl.handle.net/2077/21523
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| 17. |
- Herlenius, Gustaf, 1961, et al.
(author)
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Stable long-term renal function after pediatric liver transplantation.
- 2010
-
In: Pediatric transplantation. - : Wiley. - 1399-3046 .- 1397-3142. ; 14:3, s. 409-16
-
Journal article (peer-reviewed)abstract
- Long-term exposure to calcineurin inhibitors increases the risk of CKD in children after LT. The aims of this study were to study renal function by measuring GFRm before and yearly after LT, to describe the prevalence of CKD (stage III: GFR 30-60 mL/min/1.73 m(2)) and to investigate if age and underlying liver disease had an impact on long-term renal function. Thirty-six patients with a median age of 2.9 years (0.1-16 yr) were studied. Median follow-up was 6.5 (2-14 yr). GFRm decreased significantly during the first six months post-transplantation with 23% (p < 0.001). Thereafter renal function stabilized. At six months, 17% (n = 5) of the children presented CKD stage III and at five yr the prevalence of CKD III was 18% in 29 children. However, in 13 children with a 10-year follow-up it was 0%. None of the children required renal replacement therapy after LT. When analyzing renal function of those children younger than two yr (n = 14) and older than two yr (n = 17) at the time of transplantation, we found that in both cohorts the filtration rate remained remarkably stable during the five-yr observational period. However, there was a statistically significant (p < 0.05) difference in the percentual decrease in GFRm between the groups during the first six months after LT 13% and 31%, respectively. Baseline GFRm according to diagnosis did not differ between the groups. During the first six months after LT, patients transplanted for hepatic malignancy (n = 6) and those with metabolic liver disease (n = 4) had a percentage loss of GFRm of 32% and 35%, respectively. The corresponding loss of GFRm in patients with other diseases was 10-19%. Six months post-transplantation mean GFRm in the group with malignant liver disease was 65 +/- 15 mL/min/1.73 m(2) and in the group with other diseases (n = 24) 82 +/- 17 mL/min/1.73 m(2) (p < 0.05). At one, three and five yr post-transplantation there was no longer a statistically significant difference between these cohorts. Our findings suggest that there can be a long-term recovery of renal function after LT in children.
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| 18. |
- Herlenius, Gustaf, et al.
(author)
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Tarmtransplantation : experimentell terapi som blivit realistiskt alternativ
- 2004
-
In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 101:38, s. 2874-2878
-
Journal article (peer-reviewed)abstract
- Outcome after intestinal transplantation has improved dramatically since the introduction of novel immunosuppressive agents and refined surgical techniques. Small bowel transplantation is now considered to be the best treatment modality for patients with life threatening complications of intestinal failure and parenteral nutrition. We hereby review the international experience as well as the first ten cases of intestinal transplantation performed in Sweden.
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| 19. |
- Kullberg-Lindh, Carola, 1959, et al.
(author)
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Epstein-Barr virus DNA monitoring in serum and whole blood in pediatric liver transplant recipients who do or do not discontinue immunosuppressive therapy
- 2017
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In: Pediatric Transplantation. - : Wiley. - 1397-3142 .- 1399-3046. ; 21:5
-
Journal article (peer-reviewed)abstract
- © 2016 John Wiley & Sons A/S.The rate of PTLD can be reduced by weaned IS guided by monitoring of EBV DNA. In this single-center retrospective case series study, we analyzed how reduction in IS influenced EBV DNA levels in whole blood and serum in 30 children during the first year after liver transplantation, and how these levels were related to symptoms putatively due to EBV. Primary and reactivated EBV infection was seen in 18 (60%) and eight patients (27%), respectively. Thirteen patients (42%) developed chronic high load the first year post-transplant. IS was successfully discontinued in six patients the first year post-transplant and in another two patients within 3 years. EBV DNA levels were reduced, but persisted long term in all the eight patients who had IS completely withdrawn. There was no case of PTLD. In summary, EBV DNAemia and chronic high load were very common after pediatric liver transplantation. Liver graft tolerance facilitates radical reduction in IS treatment, which may prevent PTLD, but EBV DNAemia may persist long term after discontinued IS.
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| 20. |
- Lukes, D. J., et al.
(author)
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Late mortality in 679 consecutive liver transplant recipients: the Gothenburg liver transplant experience
- 2006
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In: Transplantation proceedings. - 0041-1345. ; 38:8, s. 2671-2
-
Journal article (peer-reviewed)abstract
- PURPOSE: Liver transplantation (OLT) is an established treatment with excellent early outcome. However, the long-term results are hampered by side effects of immunosuppression, cardiovascular morbidity, recurrent disease, and chronic rejection. We analyzed causes of late death (>/=2 years post-OLT) in 679 consecutive primary recipients in our institution. MATERIALS AND METHODS: A total of 679 primary OLT recipients including those retransplanted within 3 months between January 1985 and August 2005 were identified; 460 (67.7%) patients survived >/=2 years. The indications were cholestatic disease (35.1%), postviral (11.4%), alcoholic (12.9%), fulminant hepatic failure (7.0%), cryptogenic (3.1%), autoimmune hepatitis (4.8%), malignancy (7.7%), and others (18.0%). Sixty three patients (9.3%) died >/=2 years post-OLT. For 51 patients, sufficient records were present to establish the cause of death. RESULTS: Four hundred sixty (67.7%) patients survived >/=2 years. Their median age was 58 years with, 43.7% older than 60 and 11.1% older than 70 years. Sixty three patients (9.3%) died at a median time of 69 +/- 4.8 months post-primary OLT; 49.1% died of malignancy and 13.7% of vascular complications and infectious complications respectively. CONCLUSIONS: Late mortality in our material is mainly due to malignant disease. Compared to other published reports on late mortality, the proportion of malignancy, especially recurrent, as cause of late death is higher. This might reflect a more generous approach toward accepting older patients and a higher proportion of patients with various malignant diseases accepted for OLT.
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| 21. |
- Norén, Åsa, et al.
(author)
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Liver Graft Proteomics Reveals Potential Incipient Mechanisms behind Early Renal Dysfunction after Liver Transplantation
- 2022
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 23:19
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Journal article (peer-reviewed)abstract
- Acute kidney injury (AKI) is frequent after liver transplantation (LT) and correlates with later development of chronic kidney disease. Its etiology is multifactorial and combines pre-, intra-, and postoperative factors. Additionally, the liver graft itself seems an important element in the development of AKI, yet the detailed mechanisms remain unclear. We hypothesized that grafts of LT recipients developing significant early AKI may show distinct proteomic alterations, and we set out to identify proteome differences between LT recipients developing moderate or severe AKI (n = 7) and LT recipients without early renal injury (n = 7). Liver biopsies obtained one hour after reperfusion were assessed histologically and using quantitative proteomics. Several cytokines and serum amyloid A2 (SAA2) were analyzed in serum samples obtained preoperatively, 2-4 h, and 20-24 h after graft reperfusion, respectively. LT induced mild histological alterations without significant differences between groups but uniformly altered liver function tests peaking on postoperative day 1, with a trend towards more severe alterations in patients developing AKI. Global quantitative proteomic analysis revealed 136 proteins differing significantly in their expression levels (p < 0.05, FC 20%): 80 proteins had higher and 56 had lower levels in the AKI group. Most of these proteins were related to immune and inflammatory responses, host defense, and neutrophil degranulation. No differences between the studied pro- and anti-inflammatory cytokines or SAA2 between groups were found at any moment. Our results suggest that grafts of LT patients who develop early AKI reveal a distinct proteome dominated by an early yet prominent activation of the innate immunity. These findings support the hypothesis that AKI after LT may be favored by certain graft characteristics.
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| 22. |
- Norén, Åsa, et al.
(author)
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Perioperative kidney injury in liver transplantation: a prospective study with renal histology and measured glomerular filtration rates
- 2022
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 57:5, s. 595-602
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Journal article (peer-reviewed)abstract
- Background Acute kidney injury (AKI) is frequent after liver transplantation (LT), with impact on graft function, morbidity and mortality. Although multifactorial, the pathophysiology of perioperative kidney injury remains unclear. Our aims were to analyze the frequency, evolution and risk factors for kidney impairment during the peri- and early post-operative period. Methods In a prospective, single-center study of 27 adult patients undergoing first single-organ LT, we analyzed measured glomerular filtration rate (mGFR) pre-transplant, at post-operative day (POD) 10, and at 1, 3, 12 and 36 months. Kidney and liver graft biopsies were performed during LT. Results A median mGFR decline of 45% was detected from pre-transplant to POD 10, correlating strongly with the mGFR evolution from baseline to 12 months (rs = 0.80, p<.001) and baseline to 36 months (rs = 0.82, p<.001). AKI occurred in 59% of recipients within 48 h of LT, notably before the introduction of calcineurin inhibitors on POD 3. AKI was strongly associated with mGFR at 12 and 36 months. Kidney and liver graft biopsies showed only minor histological changes. Donor and recipient body mass index, recipient age, model of end-stage liver disease score, diagnosis of hepatitis C, donor cause of death, as well as bleeding, transfusions and duration of the anhepatic phase correlated with early kidney dysfunction. Conclusion The greatest decline in mGFR was evident within 10 days and AKI within hours of LT, irrespective of baseline mGFR and before introduction of calcineurin inhibitors. Very early post-LT kidney injury has substantial consequences for long-term kidney function.
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| 23. |
- Olausson, Michael, 1956, et al.
(author)
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Orthotopic liver or multivisceral transplantation as treatment of metastatic neuroendocrine tumors
- 2007
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In: Liver transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1527-6465 .- 1527-6473. ; 13:3, s. 327-33
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Journal article (peer-reviewed)abstract
- Liver transplantation can be a therapeutic option for individual patients with neuroendocrine tumors metastatic only to the liver. In this consecutive series of 15 patients (5 multivisceral and 10 orthotopic liver transplantations) with well-differentiated carcinoids, or endocrine pancreatic tumors, we allowed higher proliferation rate (Ki67 <10%), large tumor burden, and higher age than previous studies. Liver transplantation offered good relief of symptoms, long disease-free intervals, and potential cure in individual patients. The survival of grafts and patients compared well with transplantation for benign disease. The overall 5-year survival was 90%. The recurrence-free survival of both multivisceral and liver transplantation related to the time after transplantation (about 20% at 5 years) despite inclusion of patients with higher risk. In conclusion, the critical prognosticators for long-term outcome still remain to be defined. The experience with multivisceral transplantation for patients with endocrine tumors of the pancreatic head is still limited.
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| 24. |
- Oltean, Mihai, 1976, et al.
(author)
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Endoscopic ultrasound in the monitoring of the intestinal allograft
- 2022
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In: Bmj Open Gastroenterology. - : BMJ. - 2054-4774. ; 9:1
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Journal article (peer-reviewed)abstract
- Objective Chronic rejection (CR) of the small intestinal allograft includes mucosal fibrosis, bowel thickening and arteriopathy in the outer wall layers and the mesentery. CR lacks non-invasive markers and reliable diagnostic methods. We evaluated endoscopic ultrasound (EUS) as a novel approach for monitoring of the intestinal allograft with respect to CR. Design In intestinal graft recipients, EUS and enteroscopy with ileal mucosal biopsy were performed via the ileostomy. At EUS, the wall thickness of the intestinal graft was measured in standard mode, whereas the resistive index (RI) of the supplying artery was assessed in pulsed Doppler mode. At enteroscopy, the intestinal mucosa was assessed. Findings were compared with histopathology and clinical follow-up. Results EUS was successfully performed in all 11 patients (adequate clinical course (AC) n=9; CR n=2) after a median interval of 1537 days (range: 170-5204), post-transplantation. The total diameter of the wall (layer I-V) was comparable in all patients. Meanwhile, the diameter of the outermost part (layer IV-V; that is, muscularis propria-serosa) was among the two CR patients (range: 1.3-1.4 mm) in the upper end of measurements as compared with the nine AC patients (range: 0.5-1.4 mm). The RI was >0.9 in both CR patients, while the RI was <= 0.8 in all AC patients. Both CR patients had abnormal findings at enteroscopy and histopathology and deceased during follow-up. Conclusion EUS is a promising tool providing detailed information on the intestinal graft morphology and rheology, which may be used for assessment of potential CR in long-term follow-up of intestinal allograft recipients.
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| 25. |
- Oltean, Mihai, 1976, et al.
(author)
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Improved intestinal preservation using an intraluminal macromolecular solution: evidence from a rat model.
- 2010
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In: Transplantation. - 1534-6080. ; 89:3, s. 285-90
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Journal article (peer-reviewed)abstract
- BACKGROUND: Intestinal preservation injury consists of progressive submucosal edema, with fluid originating both from the lumen and the interstitium. Although vascular flushing aims to control electrolyte shifts in the tissue, the lumen is not addressed, and luminal water and electrolytes enter the tissue during ischemia. Because macromolecular solutions may retain water and electrolytes intraluminally, we investigated whether these solutions administered intraluminally may alleviate preservation injury. METHODS: Sprague-Dawley rat intestines were perfused with University of Wisconsin solution. After excision of the intestines, we intraluminally introduced solutions containing polyethylene glycol 3350 with high (125 mEq) or low (65 mEq) sodium before cold preservation. Controls underwent only vascular flush. After 8, 14, or 20 hr of cold storage, the intestines were analyzed for extent of tissue injury, water retention, brush-border maltase, and tight junction proteins zonula occludens-1 and claudin-3. RESULTS: Intraluminal composition changed over time, indicating sodium absorption and potassium secretion. After 8 and 14 hr of cold storage, intestines from the low-sodium group had the best morphology and least edema, followed by the controls. Maltase activity slightly decreased in all groups over time and was not affected by the intraluminal polyethylene glycol solutions. Various degrees of delocalization and degradation of zonula occludens-1 and claudin-3 were recorded within the tight junctions, with the most significant effects in intestines from the high-sodium group. CONCLUSIONS: Intraluminal macromolecular solutions may modulate the preservation injury in University of Wisconsin- perfused intestines. Low-sodium solutions administered immediately before preservation may improve preservation injury, but high-sodium solutions may be detrimental.
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| 26. |
- Oltean, Mihai, 1976, et al.
(author)
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Infectious complications after multivisceral transplantation in adults.
- 2006
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In: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 38:8, s. 2683-5
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Journal article (peer-reviewed)abstract
- It is thought that multivisceral transplantation requires high levels of immunosuppression and therefore, patients run an increased risk of infection. We retrospectively reviewed our center's experience with clinically relevant infectious complications. PATIENTS: Between 2000 and 2005, 10 adult patients underwent multivisceral transplantation. Two immunosuppression protocols were used: between 2000 and 2003, a high immunosupression protocol (six patients; daclizumab induction, tacrolimus trough levels >20 ng/mL and steroids) and an immunomodulatory, low imunosuppression scheme from 2003 onward (four patients; ATG induction, tacrolimus levels 5 to 10 ng/mL, no steroids). Standard antimicrobial prophylaxis consisted of vancomycin, meropenem, and amphotericin B. Cytomegalovirus (CMV) prophylaxis was used in all but first two cases. Donor and recipient CMV status were D+/R+ (n = 7), D+/R- (n = 2), D-/R+ (n = 1). RESULTS: The median follow-up period was 627 days (range, 19 to 2207 days). A total of 47 infectious episodes were recorded in all patients (range 1 to 14 per patient). The etiology was bacterial in 32 (69%), viral in 8 (17%), and fungal in 7 (14%) cases. The most frequent were catheter related (n = 13) followed by respiratory (n = 7), intraabdominal (n = 6), and wound infections (n = 5). Symptomatic viral infection of the graft (CMV gastritis or enteritis, adenoviral enteritis) was also encountered. Epstein-Barr virus was transiently detected in the serum of nine patients, one of whom later developed posttransplant lymphoproliferative disorder (PTLD). Three deaths all among patients receiving high immunosuppression were owing to infectious complications: pulmonary PTLD at 4 months posttransplantation, ruptured mycotic aneurysm after 8 weeks, and sepsis after 3 weeks. CONCLUSIONS: Infections accounted for a high morbidity after multivisceral transplantation, representing the leading cause of mortality. Exhaustive monitoring, early antimicrobial intervention, and lower immunosuppression may improve the outcome.
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| 27. |
- Oltean, Mihai, 1976, et al.
(author)
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Intraluminal Polyethylene Glycol Stabilizes Tight Junctions and Improves Intestinal Preservation in the Rat
- 2012
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 12:8, s. 2044-2051
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Journal article (peer-reviewed)abstract
- Rapidly progressing mucosal breakdown limits the intestinal preservation time below 10 h. Recent studies indicate that intraluminal solutions containing polyethylene glycol (PEG) alleviate preservation injury of intestines stored in UW-Viaspan. We investigated whether a low-sodium PEG solution is beneficial for intestines stored in histidine-tryptophane-ketoglutarate (HTK) preservation solution. Rat intestines used as control tissue (group 1) were perfused with HTK, groups 2 and 3 received either a customized PEG-3350 (group 2) or an electrolyte solution (group 3) intraluminally before cold storage. Tissue injury, brush-border maltase activity, zonula occludens-1 (ZO-1) and claudin-3 expression in the tight junctions (TJ) were analyzed after 8, 14 and 20 h. We measured epithelial resistance and permeability (Ussing chamber) after 8 and 14 h. Group 2 had superior morphology while maltase activity was similar in all groups. TJ proteins rapidly decreased and decolocalized in groups 1 3; these negative events were delayed in group 2, where colocalization persisted for about 14 h. Intestines in group 2 had higher epithelial resistance and lower permeability than the other groups. These results suggest that a customized PEG solution intraluminally reduces the intestinal preservation injury by improving several major epithelial characteristics without negatively affecting the brush-border enzymes or promoting edema.
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| 28. |
- Oltean, Mihai, 1976, et al.
(author)
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Laser-Doppler flowmetry in the monitoring of the human intestinal allograft: a preliminary report.
- 2006
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In: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 38:6, s. 1723-5
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Journal article (peer-reviewed)abstract
- During acute rejection, graft endothelium becomes a prime target for recipient immune cells. Animal studies have shown reduced microvascular perfusion, probably due to increased endothelial-leukocyte interaction and endothelial impairment, leading to graft damage. Using laser-Doppler flowmetry (LDF), we correlated the microvascular blood flow in the intestinal mucosa of five patients receiving multivisceral grafts with clinical events and pathology results. Measurements (n = 75) were performed during the first 4 weeks posttransplantation by inserting the LDF flexible probe through the ileostomy for 25 to 30 cm. Forty-six of the 75 measurements were performed within 24 hours of endoscopy and biopsy. In uncomplicated cases, we recorded a gradual increase in mucosal perfusion during the first week posttransplantation that presumably reflected regeneration after reperfusion injury. Increased mucosal perfusion did not seem to correlate with rejection or other adverse clinical events. Sudden and sustained decreases in mucosal perfusion by 30% or more compared to the previous measurements were associated with septic episodes, rejection, or both. LDF revealed a good sensitivity in monitoring the intestinal microcirculation. It was able to indicate perfusion changes associated with acute rejection. The relatively low specificity of LDF may be compensated by the low invasivity, allowing frequent investigation. LDF may be an additional tool for routine monitoring of intestinal allografts.
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| 29. |
- Oltean, Mihai, 1976, et al.
(author)
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Monitoring of the intestinal mucosal perfusion using laser Doppler flowmetry after multivisceral transplantation
- 2005
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In: Transplantation proceedings. - 0041-1345. ; 37:8, s. 3323-4
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Graft endothelium constitutes a prime target during acute rejection. Infiltration of T cells, monocytes, and enhanced endothelial-leukocyte interactions result in microvascular impairment and altered perfusion. MATERIALS AND METHODS: We measured mucosal blood flow using a laser Doppler flowmeter in three patients undergoing multivisceral transplantation. Thirty-seven measurements were performed through the ileostomy over the first 4 weeks posttransplantation. Most measurements were performed within a 24-hour interval from endoscopy and biopsy. RESULTS: Mucosal perfusion increased throughout the first postoperative week and eventually stabilized around levels specific for each patient. Mucosal perfusion remained stable during graft pancreatitis, but decreased 35% to 55% from baseline (the average value of the previous measurements) during acute rejection and sepsis. During the first week posttransplantation there was a gradual increase in mucosal perfusion, which might reflect regeneration after reperfusion injury. Increased mucosal perfusion did not seem to correlate with rejection or other adverse clinical events. A sudden decrease in mucosal perfusion of 30% or more compared to the previous measurements was associated with septic episodes and/or rejection.
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| 30. |
- Oltean, Mihai, 1976, et al.
(author)
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Recipient Hyperbilirubinemia May Reduce Ischemia-Reperfusion Injury but Fails to Improve Outcome in Clinical Liver Transplantation
- 2016
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In: Gastroenterology Research and Practice. - : Hindawi Limited. - 1687-6121 .- 1687-630X. ; 11:6
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Journal article (peer-reviewed)abstract
- Background. Exogenous bilirubin may reduce experimental ischemia-reperfusion injury (IRI) due to its antioxidant properties. We studied if early graft exposure to high bilirubin levels in the recipient affects the early IRI and outcomes after liver transplantation (LTx). Methods. In 427 LTx patients, the AUROC curve based on bilirubin and AST at day 1 identified a cutoff of 2.04mg/dL for the recipient pretransplant bilirubin. Recipients were grouped as having low (group L, n = 152) or high (group H, n = 275) bilirubin. Both groups had similar donor-related variables (age, preservation time, donor BMI > 28, and donor risk index (DRI)). Results. Alanine (ALT) and aspartate (AST) aminotransferase levels were higher in group L at day 1; ALT levels remained higher at day 2 in group L. LTx from high risk donors (DRI > 2) revealed a trend towards lower transaminases during the first two days after transplantation in group H. One month and 1-year patient survival were similar in groups L and H. High preoperative bilirubin did not affect the risk for early graft dysfunction (EGD), death, or graft loss during the first year after transplantation nor the incidence of acute rejection. LTx using donors with DRI > 2 resulted in similar rates of EGD in both groups. Conclusion. Increased bilirubin appears to reduce the early IRI after LTx yet this improvement was insufficient to improve the clinical outcome.
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| 31. |
- Patil, Pradeep B, 1982, et al.
(author)
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Recellularization of acellular human small intestine using bone marrow stem cells.
- 2013
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In: Stem cells translational medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 2:4, s. 307-15
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Journal article (peer-reviewed)abstract
- We aimed to produce an acellular human tissue scaffold with a view to test the possibility of recellularization with bone marrow stem cells to produce a tissue-engineered small intestine (TESI). Human small-bowel specimens (n = 5) were obtained from cadaveric organ donors and treated sequentially with 6% dimethyl sulfoxide in hypotonic buffer, 1% Triton X-100, and DNase. Each small intestine (SI) piece (6 cm) was recellularized with EPCAM+ and CD133+ allogeneic bone marrow stem cells. Histological and molecular analysis demonstrated that after decellularization, all cellular components and nuclear material were removed. Our analysis also showed that the decellularized human SI tissue retained its histoarchitecture with intact villi and major structural proteins. Protein films of common extracellular matrix constituents (collagen I, laminin, and fibronectin) were found in abundance. Furthermore, several residual angiogenic factors were found in the decellularized SI. Following recellularization, we found viable mucin-positive goblet cells, CK18+ epithelial cells in villi adjacent to a muscularis mucosa with α-actin+ smooth muscle cells, and a high repopulation of blood vessels with CD31+ endothelial cells. Our results show that in the future, such a TESI would be ideal for clinical purposes, because it can be derived from the recipient's own immunocompatible bone marrow cells, thus avoiding the use of immunosuppression.
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| 32. |
- Tarnow, H., et al.
(author)
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Outcome of renal transplantation subsequent to liver, heart, or lung transplantation
- 2006
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In: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 38:8, s. 2649-50
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Journal article (peer-reviewed)abstract
- Renal dysfunction is a growing problem after liver, heart, or lung transplantation with the subsequent need for dialysis or renal transplantation. The aim of this study was to analyze the outcome after a subsequent kidney transplantation (secondary kidney transplantation) in liver, heart, or lung transplantation recipients. All secondary kidney transplantation patients from 1985 to 2006 were identified for the cause of kidney failure, time after initial transplantation, and current kidney function. One thousand two hundred three patient charts were reviewed including 22 (1.8%) secondary kidney transplantations: eight after lung, eight after heart, and six after liver transplantation. Renal failure was the result of perioperative renal failure (n = 3), toxic effects of cyclosporine (n = 16), a combination of cyclosporine nephrotoxicity and vascular ischemia (n = 3), or chronic renal failure due to polycystic kidney disease (n = 1). The median time after the initial organ transplantation was 114 months (range 30 to 241 months). The most recent median creatinine value was 103 micromol/L (82 to 704 micromol/L). Renal transplant rejection was noted in five patients: four in the lung transplant group, and one after heart transplantation. Three patients were deceased, one from secondary renal failure. One renal allograft was removed after renal artery thrombosis. In conclusion, there is sometimes a need for subsequent kidney transplantation after liver, heart, or lung transplantation. The outcome of renal transplantation subsequent to liver, heart, or lung transplantation is good with satisfactory renal function in this study population.
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| 33. |
- Varkey, Jonas, 1980, et al.
(author)
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Fifteen years' experience of intestinal and multivisceral transplantation in the Nordic countries.
- 2015
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In: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 50:3, s. 278-90
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Journal article (peer-reviewed)abstract
- Intestinal and multivisceral transplantation have gained acceptance as treatment modalities for patients with: intestinal failure and life-threatening complications of parenteral nutrition (PN), rare cases of vascular abdominal catastrophes and selected cases of low-grade neoplastic tumors such as neuroendocrine pancreatic tumors and desmoids involving the mesenteric root. The aim was to describe the survival and nutritional outcome in the transplanted Nordic patients and the complications attributed to this procedure.
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| 34. |
- Varkey, Jonas, 1980, et al.
(author)
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Initial Experience of Video Capsule Endoscopy After Intestinal Transplantation.
- 2016
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In: Transplantation direct. - 2373-8731. ; 2:12
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Journal article (peer-reviewed)abstract
- Intestinal transplantation is a procedure which inflicts immunological and infectious complications that affect the transplanted graft, posing both diagnostic and therapeutic challenges. Video capsule endoscopy (VCE) offers easy access to the entire small intestine and presents itself as an interesting option. However, at present, no studies evaluating the usefulness of video capsule endoscopies in this setting have been published. Our aim was to evaluate the usefulness of VCE in detecting complications that arise after intestinal transplantation.We included 7 adult patients with either isolated intestine (n = 1) or multivisceral grafts (n = 6). These patients underwent 12 VCE between 2004 and 2015 at the Sahlgrenska University Hospital. The median age was 42 (21-67) years (4 women/3 men). VCE was used in clinical situations where the conventional diagnostic methods failed to provide answers to the clinical question.Indications for the procedure were: suspicion of rejection (n = 4 examinations), gastrointestinal dysmotility (n = 4 examinations), high stomal output (n = 2 examinations), suspicion of lymphoproliferative disease in the transplanted graft (n = 1 examination), and clinical surveillance (n = 1 examination). The median time after transplantation for performing an examination was 740 (26-3059) days. VCE was useful in 83% of the examinations and the results influenced the planned management. The overall agreement between VCE findings and biopsies was moderate (κ = 0.54, P = 0.05) but increased when comparing the presence of inflammation/rejection (κ = 0.79, P < 0.001).VCE is a promising diagnostic method after intestinal transplantation. However, larger studies are needed to evaluate its potential risks and gains.
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| 35. |
- Varkey, Jonas, 1980, et al.
(author)
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The endoscopic surveillance of the transplanted small intestine: a single center experience and a proposal for a grading score.
- 2018
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In: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 53:2, s. 134-139
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Journal article (peer-reviewed)abstract
- Microscopic examination of endoscopic biopsies forms the basis of acute cellular rejection (ACR) monitoring after intestinal transplantation (ITx). The endoscopy findings during acute rejection (AR) are known but a grading system for its severity is lacking. We designed and implemented a five-stage grading score based on acknowledged endoscopic features of AR, to allow a faster preliminary diagnosis of AR and intra- and interpatient comparisons.Two investigators reviewed and graded the endoscopy reports after 28 ITx using a novel score and correlated the results with pathology findings.We reviewed 512 ileoscopies: 370 examinations (74%) were normal (G0), 59 had mild alterations (erythema, edematous villi-G1) and 36 showed moderate changes (erosions, blunted villi-G2); 17 ileoscopies revealed advanced changes (ulcerations, villus loss-G3). In 18 endoscopies the changes were severe (mucosal loss-G4). Inter-reviewer agreement was very good (kappa=0.81). Biopsies from 86 endoscopy sessions (17%) indicated ACR with 63 cases having moderate or severe ACR. For mild ACR the sensitivity of the score was 29% and the specificity was 86% whereas the positive (PPV) and negative predictive values (NPVs) were 14% and 93% respectively. During advanced ACR the sensitivity and specificity were 92% and 86%, respectively whereas the PPV and NPV were 49% and 98% respectively.Endoscopy alone has a limited ability to reliably diagnose intestinal ACR. We suggest a novel grading score summarizing ACR findings and allowing comparisons between intestinal graft endoscopies.
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| 36. |
- Åberg, Fredrik, et al.
(author)
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Everolimus and long-term decline in renal function after liver transplantation: real-life experience with measured GFR
- 2020
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:6, s. 718-724
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Journal article (peer-reviewed)abstract
- Switching from calcineurin-inhibitors (CNI) to everolimus >6-12-months after liver transplantation (LT) seems inefficient in improving renal function, but whether everolimus halts further renal-function decline compared to low-dose CNI remains unclear. In a retrospective single-center study of everolimus after LT (2008-2016) with routine measured glomerular filtration rates (mGFR;Cr-51-EDTA- or iohexol clearance), we compared by propensity-score matching everolimus therapy to low-dose CNI therapy. The study comprised 36 patients with everolimus introduced on average 22 months post-LT (range 2-105 months, median follow-up 3.4 years), and 36 matched controls. Everolimus introduction was associated with a mean improvement in mGFR of 7 mL/min up to 1 year (p = .003), restricted to patients switched 5 ng/mL. The differences between the everolimus group and controls in delta-mGFR from baseline to 1 year (7.3 vs 4.3 mL/min,p = .25) or 1-year to last follow-up (-0.8 vs -0.2 mL/min/year,p = .71) were non-significant. Proportions with mGFR decline >3 mL/min/year were similar between groups (11% and 14%,p = 1.00). Everolimus was stopped in three patients (8%), and acute rejection occurred in 17%. In conclusion, despite an early improvement in renal function after everolimus introduction, we found no evidence that everolimus halts the long-term mGFR decline compared to continued low-dose CNI therapy. Due to retrospective design, small sample size and heterogenous characteristics, definite conclusions require prospective studies.
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