Journal Of Transplantation[JOURNAL]
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200 papers
Detection of postoperative intestinal ischemia in small bowel transplants.
Birke-Sorensen H
J Transplant · 2012 · PMID 23209878 · Full text
Small bowel transplantation is acknowledged as auto- and allotransplantation. In both instances, there is up to a 4%-10% risk of postoperative ischemia, and as the small bowel is extremely susceptible to ischemia, the ti...
Small bowel transplantation is acknowledged as auto- and allotransplantation. In both instances, there is up to a 4%-10% risk of postoperative ischemia, and as the small bowel is extremely susceptible to ischemia, the timely diagnosis of ischemia is important. The location of the transplant, whether it is buried in the abdominal cavity or in the neck region, increases the challenge, as monitoring becomes more difficult and the consequences of neglect more dangerous. All methods for the early detection of postoperative ischemia in small bowel transplants are described together with the requirements of the ideal monitoring method. A small bowel transplant can be inspected directly or indirectly; the blood flow can be monitored by Doppler or by photoplethysmography, and the consequences of the blood flow can be monitored. The ideal monitoring method should be reliable, fast, minimally invasive, safe, objective, easy, cheap, and comfortable. No monitoring methods today fulfill the criteria of the ideal monitoring method, and evidence-based guidelines regarding postoperative monitoring cannot be made. The choice of whether to implement monitoring of ischemia-and if so, which method to choose-has to be made by the individual surgeon or center.
Gene transfer of heme oxygenase-1 using an adeno-associated virus serotype 6 vector prolongs cardiac allograft survival.
Evans JM, Navarro S, Doki T … +3 more , Stewart JM, Mitsuhashi N, Kearns-Jonker M
J Transplant · 2012 · PMID 23125915 · Full text
Introduction. Allograft survival can be prolonged by overexpression of cytoprotective genes such as heme oxygenase-1 (HO-1). Modifications in vector design and delivery have provided new opportunities to safely and effec...
Introduction. Allograft survival can be prolonged by overexpression of cytoprotective genes such as heme oxygenase-1 (HO-1). Modifications in vector design and delivery have provided new opportunities to safely and effectively administer HO-1 into the heart prior to transplantation to improve long-term graft outcome. Methods. HO-1 was delivered to the donor heart using an adeno-associated virus vector (AAV) with a pseudotype 6 capsid and vascular endothelial growth factor (VEGF) to enhance myocardial tropism and microvascular permeability. Survival of mouse cardiac allografts, fully or partially mismatched at the MHC, was determined with and without cyclosporine A. Intragraft cytokine gene expression was examined by PCR. Results. The use of AAV6 to deliver HO-1 to the donor heart, combined with immunosuppression, prolonged allograft survival by 55.3% when donor and recipient were completely mismatched at the MHC and by 94.6% if partially mismatched. The combination of gene therapy and immunosuppression was more beneficial than treatment with either AAV6-HO-1 or CsA alone. IL-17a, b, e and f were induced in the heart at rejection. Conclusions. Pretreatment of cardiac allografts with AAV6-HO-1 plus cyclosporine A prolonged graft survival. HO-1 gene therapy represents a beneficial adjunct to immunosuppressive therapy in cardiac transplantation.
Tricuspid valve regurgitation after orthotopic heart transplantation: prevalence and etiology.
Berger Y, Har Zahav Y, Kassif Y … +4 more , Kogan A, Kuperstein R, Freimark D, Lavee J
J Transplant · 2012 · PMID 23097690 · Full text
Background. Tricuspid valve regurgitation (TR) after orthotopic heart transplantation (OHT) is common. The aims of this study were to determine the prevalence of TR after OHT, to examine the correlation between its devel...
Background. Tricuspid valve regurgitation (TR) after orthotopic heart transplantation (OHT) is common. The aims of this study were to determine the prevalence of TR after OHT, to examine the correlation between its development and various variables, and to determine its outcomes. Methods. All 163 OHT patients who were followed up between 1988 and 2009 for a minimal period of 12 months were divided into those with no TR/mild TR and those with at least mild-moderate TR, as assessed by doppler echocardiography. These groups were compared regarding preoperative hemodynamic variables, surgical technique employed, number of endomyocardial biopsies, number of acute cellular rejections, incidence of graft vasculopathy, and clinical outcomes. Results. At the end of the followup (average 8.2 years) significant TR was evident in 14.1% of the patients. The development of late TR was found by univariate, but not multivariate, analysis to be significantly correlated with the biatrial surgical technique (P < 0.01) and the presence of graft vasculopathy (P < 0.001). TR development was found to be correlated with the need for tricuspid valve surgery but not with an increased mortality. Conclusions. The development of TR after OHT may be related to the biatrial anastomosis technique and to graft vasculopathy.
Exenatide pretreatment improved graft function in nonhuman primate islet recipients compared to treatment after transplant only.
Buss JL, Rajab A, Essig ED … +3 more , Bergdall VK, Wang J, Osei K
J Transplant · 2012 · PMID 23056916 · Full text
The GLP-1 receptor agonist, exenatide, has previously been shown to improve insulin secretion, protect beta cells from apoptosis, and promote beta cell regeneration. We propose that pretreatment with exenatide will promo...
The GLP-1 receptor agonist, exenatide, has previously been shown to improve insulin secretion, protect beta cells from apoptosis, and promote beta cell regeneration. We propose that pretreatment with exenatide will promote islet graft survival and improve graft function. Pancreatectomized cynomolgus monkeys underwent islet allotransplantation and were treated with exenatide beginning on day 0 or day -2. A third group of animals was treated with an immunosuppressive regimen while a fourth group remained untreated. Fasting blood glucose (FBG) was used to evaluate graft function along with intravenous glucose tolerance tests (IVGTTs) performed at study endpoint (day 10 for untreated and posttransplant exenatide or day 90 for pretreatment exenatide and immunosuppression). The average FBG for pre-treated animals day 5 following transplant was 52.7 ± 14.8 mg/dl, compared to 154.3 ± 105.5 mg/dl for animals treated only following transplant, 59.4 mg/dl ±12.1 for animals treated with immunosuppression, and 265.5 ± 172.3 mg/dl for untreated animals. IVGTTs performed at study endpoint showed normal glucose and insulin curves in the pre-treated exenatide and immunosuppression groups only, with beta cell function actually improving after transplant in the pre-treated group. We conclude, therefore, that exenatide pre-treatment can successfully maintain islet graft survival in nonhuman primates.
The mode of pretransplant dialysis does not affect postrenal transplant outcomes in african americans.
Sharma A, Teigeler TL, Behnke M … +5 more , Cotterell A, Fisher R, King A, Gehr T, Posner M
J Transplant · 2012 · PMID 23008755 · Full text
Background. In previous reports with a majority of Caucasian patients, peritoneal dialysis (PD) before kidney transplantation has been associated with poor outcomes and higher rates of graft thrombosis and infectious com...
Background. In previous reports with a majority of Caucasian patients, peritoneal dialysis (PD) before kidney transplantation has been associated with poor outcomes and higher rates of graft thrombosis and infectious complications than hemodialysis (HD). We report our experience on the outcomes of prerenal transplant peritoneal dialysis in predominantly (73%) African American patient population. Methods. A retrospective data analysis of 401 kidney transplants performed at our center from 2000 to 2006 was performed. Adult recipients with at least three months of pretransplant HD or PD were included. Results. There were 339 patients on HD and 62 patients on PD. There was no difference in graft (P = 0.51) and patient survival (P = 0.52) at 1, 3, and 5-years. Patients on HD were more likely to experience delayed graft function than PD (38.8% versus 17.7%, P < 0.005). There was no difference in the incidence of vascular thrombosis or posttransplant infectious complications. When only the African American patients in the two groups were compared, there were no differences in graft or patient survival. Conclusions. Pretransplant peritoneal dialysis is associated with excellent patient and renal allograft outcomes in African Americans and does not predispose them to an increased risk of infectious or thrombotic complications.
Evaluation of protocol biopsy utility 12 months after renal transplantation: a multicenter observational analysis.
Moulin B, Merville P, Renaudin K … +8 more , Buob D, Ferlicot S, Delahousse M, Dantal J, Albano L, Barbet C, Mourad G, Noel LH
J Transplant · 2012 · PMID 22988484 · Full text
The clinical merit of surveillance kidney graft biopsies remains controversial. A retrospective, multicenter analysis evaluated 12-month surveillance biopsies (SB, 154 patients) versus no SB (NSB, 138 patients (11 with d...
The clinical merit of surveillance kidney graft biopsies remains controversial. A retrospective, multicenter analysis evaluated 12-month surveillance biopsies (SB, 154 patients) versus no SB (NSB, 138 patients (11 with diagnostic biopsy)) in patients >18 months posttransplant with estimated GFR (eGFR) ≥30 mL/min. The primary objective was to describe renal function at 18 months post-transplant in patients with or without SB at month 12. Globally, most recipients in both cohorts were at low immunological risk (<10% of patients with PRA ≥30%). The immunosuppressive regimen remained unchanged following more than half of SB that exhibited chronic lesions (18/33, 54.5%). Mean (SD) eGFR at month 18 (primary endpoint) was 56 (19) mL/min/1.73 m² with SB and 54 (15) mL/min/1.73 m² with NSB (P = 0.48). In the SB group, slight nonspecific changes were observed in 51 cases, rejection (acute or chronic) in 6 cases, CNI-related toxicity in 15 cases, recurrence of initial disease in two cases, and interstitial fibrosis/tubular atrophy (IF/TA) in 83 cases (71.6%), of which 35 cases (30.2%) were grade II/III lesions. eGFR <50 mL/min/1.73 m² at month 6 predicted IF/TA grade II or III (OR 3.85, 95% CI 1.64, 9.05, P < 0.002). SB at 12 months posttransplant did not prompt significant modification of immunosuppression, and no renal benefit was observed.
Stem cells as a tool to improve outcomes of islet transplantation.
Sims E, Evans-Molina C
J Transplant · 2012 · PMID 22970344 · Full text
The publication of the promising results of the Edmonton protocol in 2000 generated optimism for islet transplantation as a potential cure for Type 1 Diabetes Mellitus. Unfortunately, follow-up data revealed that less th...
The publication of the promising results of the Edmonton protocol in 2000 generated optimism for islet transplantation as a potential cure for Type 1 Diabetes Mellitus. Unfortunately, follow-up data revealed that less than 10% of patients achieved long-term insulin independence. More recent data from other large trials like the Collaborative Islet Transplant Registry show incremental improvement with 44% of islet transplant recipients maintaining insulin independence at three years of follow-up. Multiple underlying issues have been identified that contribute to islet graft failure, and newer research has attempted to address these problems. Stem cells have been utilized not only as a functional replacement for β cells, but also as companion or supportive cells to address a variety of different obstacles that prevent ideal graft viability and function. In this paper, we outline the manners in which stem cells have been applied to address barriers to the achievement of long-term insulin independence following islet transplantation.
De Novo Donor-Specific HLA Antibody Development and Peripheral CD4(+)CD25(high) Cells in Kidney Transplant Recipients: A Place for Interaction?
Alberu J, Vargas-Rojas MI, Morales-Buenrostro LE … +6 more , Crispin JC, Rodríguez-Romo R, Uribe-Uribe NO, Carrasco G, Gómez-Martín D, Alcocer-Varela J
J Transplant · 2012 · PMID 22970343 · Full text
The aim of this study was to determine whether the abundance of regulatory T cells (Tregs) (CD4(+)CD25(high)) affects the de novo development of anti-HLA donor-specific antibodies (DSAs) in kidney transplant recipients (...
The aim of this study was to determine whether the abundance of regulatory T cells (Tregs) (CD4(+)CD25(high)) affects the de novo development of anti-HLA donor-specific antibodies (DSAs) in kidney transplant recipients (KTRs). Methods. Unsensitized (PRA ≤ 10%, no DSA) adult primary KTRs who received a living (83%) or deceased (17%) KT in our Institution during 2004/2005 were included. DSA testing was performed monthly, and Tregs were quantified by flow cytometry every 3 months, during the 1st year after KT. All patients received triple drug immunosuppressive therapy (CNI + MMF or AZA + PDN); 83% received anti-CD25. Results. 53 KTRs were included; 32% developed DSA during the 1st year after KT. Significantly lower 7-year graft survival was observed in those who developed DSA. No difference was observed in Treg numbers up to 9 months after KT, between DSA positive and negative. However, at 12 months after KT, DSA-negative patients had significantly higher numbers of Treg. Conclusions. Early development of DSA was not associated to variations in Treg abundance. The differences in Treg numbers observed at the late time point may reflect better immune acceptance of the graft and may be associated to long-term effects. Additional inhibitory mechanisms participating earlier in DSA development after KT deserve to be sought.
A prospective, multinational pharmacoepidemiological study of clinical conversion to sirolimus immunosuppression after renal transplantation.
Kasiske BL, Nashan B, Del Carmen Rial M … +5 more , Raffaele P, Russ G, Campistol J, Pescovitz MD, Keown PA
J Transplant · 2012 · PMID 22934151 · Full text
This prospective pharmacoepidemiological study examined treatment and outcomes in patients converted to sirolimus (SRL) after renal transplantation. 484 subjects in 36 centres in 7 countries were followed for up to 5 yea...
This prospective pharmacoepidemiological study examined treatment and outcomes in patients converted to sirolimus (SRL) after renal transplantation. 484 subjects in 36 centres in 7 countries were followed for up to 5 years. Principal reasons for conversion were declining graft function (146/484, 30%) and side effects of prior therapy (144/484, 30%) and the major treatment combinations after conversion were SRL ± MMF (62%), SRL + TAC (21.5%), SRL + CSA (16.5%). The cumulative probability of biopsy-confirmed acute rejection (BCAR) was 5% (n = 22), death-censored graft loss 12% (n = 56) and death 6% (n = 22), and there was no significant relationship to the treatment combination employed. Median calculated creatinine clearance was 48.4 (29.3, 64.5) mL/min at conversion, rising to 54.1 (41.2, 69.0) mL/min at month 1, 55.7 (39.0, 73.0) mL/min at month 12, 58.6 (39.7, 75.2) mL/min at two years and 60.9 (36.0, 77.0) mL/min at three years post-conversion. The most common adverse events were hypertension (47%), hyperlipidemia (26%), urinary tract infections (25%), anaemia (24%) and diarrhea (14%), and cardiac events, hyperlipemia and CMV infection were more common in patients converted during the first year. SRL was most frequently combined with MMF after conversion, but principal clinical outcomes were not significantly influenced by the treatment combination employed in normal practice.
Low CD4/CD8 Ratio in Bronchus-Associated Lymphoid Tissue Is Associated with Lung Allograft Rejection.
Shenoy KV, Solomides C, Cordova F … +3 more , Rogers TJ, Ciccolella D, Criner GJ
J Transplant · 2012 · PMID 22928088 · Full text
Background. Bronchus-associated lymphoid tissue (BALT) has been associated with lung allograft rejection in rat transplant models. In human transplant recipients, BALT has not been linked to clinically significant reject...
Background. Bronchus-associated lymphoid tissue (BALT) has been associated with lung allograft rejection in rat transplant models. In human transplant recipients, BALT has not been linked to clinically significant rejection. We hypothesize that the immunohistochemical composition of BALT varies with the presence of acute lung allograft rejection. Methods. We retrospectively examined 40 human lung allograft recipients transplanted from 3/1/1999 to 6/1/2008. Patients were grouped by frequency and severity of acute rejection based on International Society of Heart Lung Transplant (ISHLT) criteria. Transbronchial biopsies were reviewed for BALT by a blinded pathologist. BALT if present was immunohistochemically stained to determine T-and B-cell subpopulations. Results. BALT presence was associated with an increased frequency of acute rejection episodes in the first year after transplantation. Patients with a lower CD4/CD8 ratio had an increased rejection rate; however, BALT size or densities of T-cell and B-cell subpopulations did not correlate with rejection rate. Conclusion. The presence of BALT is associated with an increased frequency of rejection one year after transplant. The lower the CD4/CD8 ratio, the more acute rejection episodes occur in the first year after transplantation. The immunohistochemical composition of BALT may predict patients prone to frequent episodes of acute cellular rejection.
Islet β-Cell Mass Preservation and Regeneration in Diabetes Mellitus: Four Factors with Potential Therapeutic Interest.
Mellado-Gil JM, Cobo-Vuilleumier N, Gauthier BR
J Transplant · 2012 · PMID 22919462 · Full text
Islet β-cell replacement and regeneration are two promising approaches for the treatment of Type 1 Diabetes Mellitus. Indeed, the success of islet transplantation in normalizing blood glucose in diabetic patients has pro...
Islet β-cell replacement and regeneration are two promising approaches for the treatment of Type 1 Diabetes Mellitus. Indeed, the success of islet transplantation in normalizing blood glucose in diabetic patients has provided the proof of principle that cell replacement can be employed as a safe and efficacious treatment. Nonetheless, shortage of organ donors has hampered expansion of this approach. Alternative sources of insulin-producing cells are mandatory to fill this gap. Although great advances have been achieved in generating surrogate β-cells from stem cells, current protocols have yet to produce functionally mature insulin-secreting cells. Recently, the concept of islet regeneration in which new β-cells are formed from either residual β-cell proliferation or transdifferentiation of other endocrine islet cells has gained much interest as an attractive therapeutic alternative to restore β-cell mass. Complementary approaches to cell replacement and regeneration could aim at enhancing β-cell survival and function. Herein, we discuss the value of Hepatocyte Growth Factor (HGF), Glucose-Dependent Insulinotropic Peptide (GIP), Paired box gene 4 (Pax4) and Liver Receptor Homolog-1 (LRH-1) as key players for β-cell replacement and regeneration therapies. These factors convey β-cell protection and enhanced function as well as facilitating proliferation and transdifferentiation of other pancreatic cell types to β-cells, under stressful conditions.
A knotless technique for kidney transplantation in the mouse.
Rong S, Lewis AG, Kunter U … +2 more , Haller H, Gueler F
J Transplant · 2012 · PMID 22852070 · Full text
Mouse models of kidney transplantation are important to study molecular mechanisms of organ transplant rejection as well as to develop new therapeutic strategies aimed at improving allograft survival. However, the surgic...
Mouse models of kidney transplantation are important to study molecular mechanisms of organ transplant rejection as well as to develop new therapeutic strategies aimed at improving allograft survival. However, the surgical technique necessary to result in a viable allograft has traditionally proven to be complex and very demanding. Here, we introduce a new, simple, and rapid knotless technique for vessel anastomosis wherein the last stitch of the anastomosis is not tied to the short end of the upper tie as in the classical approach but is left free. This is a critical difference in that it allows the size of the anastomosis to be increased or decreased after graft reperfusion in order to avoid stenosis or bleeding, respectively. We compared the outcome of this new knotless technique (n = 175) with the classical approach (n = 122) in terms of local thrombosis or bleeding, time for anastomosis, and survival rates. By this modification of the suture technique, local thrombosis was significantly reduced (1.1% versus 6.6%), anastomosis time was less, and highly reproducible kidney graft survival was achieved (95% versus 84% with the classical approach). We believe that this knotless technique is easy to learn and will improve the success rates in the technically demanding model of mouse kidney transplantation.
Targeted Antibiotic Prophylaxis for Lung Transplantation in Cystic Fibrosis Patients Colonised with Pseudomonas aeruginosa Using Multiple Combination Bactericidal Testing.
Haja Mydin H, Corris PA, Nicholson A … +8 more , Perry JD, Meachery G, Marrs EC, Peart S, Fagan C, Lordan JL, Fisher AJ, Gould FK
J Transplant · 2012 · PMID 22848792 · Full text
Early infection is a recognised complication after lung transplantation in patients with cystic fibrosis (CF). Our centre uses multiple combination bactericidal testing (MCBT) when determining appropriate peritransplant...
Early infection is a recognised complication after lung transplantation in patients with cystic fibrosis (CF). Our centre uses multiple combination bactericidal testing (MCBT) when determining appropriate peritransplant prophylactic regimens. To evaluate our strategy, we compared the incidence of posttransplant infection in patients whose peritransplant antimicrobial regimens were determined using MCBT versus standard sensitivity testing. Patients with CF who were infected with Pseudomonas aeruginosa and underwent lung transplantations between 2000 and 2010 were included. Data was collected from clinical records and our microbiology database. Microorganisms cultured were mapped against antibiotic resistance, method of sensitivity testing, and antibiotics administered peritransplant. 129 patients were identified (mean age 28, male : female, 63 : 66). Fifty patients (38.8%) had antibiotics determined by MCBT. Two patients in the MCBT group developed septicaemia, 13 in the conventional group (P ≤ 0.05, 2-tailed Fisher's test). Sepsis was attributable to P. aeruginosa in one patient from the MCBT group and seven patients in the conventional group (P = 0.15). P. aeruginosa was recovered from the posttransplant pleural fluid of one patient who received MCBT-guided prophylaxis, six patients in the conventional group (P = 0.25). Patients given antibiotics based on MCBT had significantly lower rates of septicaemia and lower rates of empyema.
The major histocompatibility complex in transplantation.
Ayala García MA, González Yebra B, López Flores AL … +1 more , Guaní Guerra E
J Transplant · 2012 · PMID 22778908 · Full text
The transplant of organs is one of the greatest therapeutic achievements of the twentieth century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since...
The transplant of organs is one of the greatest therapeutic achievements of the twentieth century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the principal target of the immune response is the MHC (major histocompatibility complex) molecules expressed on the surface of donor cells. However, we should not forget that the innate and adaptive immunities are closely interrelated and should be viewed as complementary and cooperating. When a human transplant is performed, HLA (human leukocyte antigens) molecules from a donor are recognized by the recipient's immune system triggering an alloimmune response Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. This paper will present MHC, the innate and adaptive immunities, and clinical HLA testing.
CD28 family and chronic rejection: "to belatacept...And beyond!".
Silva MV, Machado JR, Rocha LP … +3 more , Castellano LR, Reis MA, Corrêa RR
J Transplant · 2012 · PMID 22720132 · Full text
Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunologica...
Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients.
Progression from Sustained BK Viruria to Sustained BK Viremia with Immunosuppression Reduction Is Not Associated with Changes in the Noncoding Control Region of the BK Virus Genome.
Memon IA, Parikh BA, Gaudreault-Keener M … +3 more , Skelton R, Storch GA, Brennan DC
J Transplant · 2012 · PMID 22701777 · Full text
Changes in the BK virus archetypal noncoding control region (NCCR) have been associated with BK-virus-associated nephropathy (BKVAN). Whether sustained viremia, a surrogate for BKVAN, is associated with significant chang...
Changes in the BK virus archetypal noncoding control region (NCCR) have been associated with BK-virus-associated nephropathy (BKVAN). Whether sustained viremia, a surrogate for BKVAN, is associated with significant changes in the BK-NCCR is unknown. We performed PCR amplification and sequencing of (1) stored urine and (2) plasma samples from the time of peak viremia from 11 patients with sustained viremia who participated in a 200-patient clinical trial. The antimetabolite was withdrawn for BK viremia and reduction of the calcineurin inhibitor for sustained BK viremia. DNA sequencing from the 11 patients with sustained viremia revealed 8 insertions, 16 transversions, 3 deletions, and 17 transitions. None were deemed significant. No patient developed clinically evident BKVAN. Our data support, at a genomic level, the effectiveness of reduction of immunosuppression for prevention of progression from viremia to BKVAN.
Identification of risk factors for vascular thrombosis may reduce early renal graft loss: a review of recent literature.
Keller AK, Jorgensen TM, Jespersen B
J Transplant · 2012 · PMID 22701162 · Full text
Renal graft survival has improved over the past years, mainly owing to better immunosuppression. Vascular thrombosis, though rare, therefore accounts for up to one third of early graft loss. We assess current literature...
Renal graft survival has improved over the past years, mainly owing to better immunosuppression. Vascular thrombosis, though rare, therefore accounts for up to one third of early graft loss. We assess current literature on transplantation, identify thrombosis risk factors, and discuss means of avoiding thrombotic events and saving thrombosed grafts. The incidence of arterial thrombosis was reported to 0.2-7.5% and venous thrombosis 0.1-8.2%, with the highest incidence among children and infants, and the lowest in living donor reports. The most significant risk factors for developing thrombosis were donor-age below 6 or above 60 years, or recipient-age below 5-6 years, per- or postoperative hemodynamic instability, peritoneal dialysis, diabetic nephropathy, a history of thrombosis, deceased donor, or >24 hours cold ischemia. Multiple arteries were not a risk factor, and a right kidney graft was most often reported not to be. Given the thrombosed kidney graft is diagnosed in time, salvage is possible by urgent reoperation and thrombectomy. Despite meticulous attentions to reduce thrombotic risk factors, thrombosis cannot be entirely prevented and means to an early detection of this complication is desirable in order to save the kidneys through prompt reoperation. Microdialysis may be a new tool for this.
A Randomized Multicenter Study Comparing a Tacrolimus-Based Protocol with and without Steroids in HCV-Positive Liver Allograft Recipients.
Neumann U, Samuel D, Trunečka P … +3 more , Gugenheim J, Gerunda GE, Friman S
J Transplant · 2012 · PMID 22690326 · Full text
Allograft reinfection with hepatitis C virus (HCV) occurs universally in liver transplant recipients. Corticosteroids can contribute to HCV recurrence. This randomized study evaluated HCV recurrence in HCV-positive liver...
Allograft reinfection with hepatitis C virus (HCV) occurs universally in liver transplant recipients. Corticosteroids can contribute to HCV recurrence. This randomized study evaluated HCV recurrence in HCV-positive liver allograft recipients using steroid-free immunosuppression. All patients received tacrolimus (TAC) at an initial dose of 0.10-0.15 mg/kg. The steroid-free arm (TAC/daclizumab (TAC/DAC, n = 67)) received daclizumab induction, and the steroid arm (TAC/steroid (TAC/STR, n = 68)) received a steroid bolus (≤ 500mg) followed by 15-20 mg/day with discontinuation after month 3. Median HCV viral load at month 12, the primary endpoint, was similar at 5.46 (0.95-6.54) IU/mL with TAC/DAC and 5.91 (0.95-6.89) IU/mL with TAC/STR. Small numerical differences in the estimated rate of freedom from HCV recurrence (19.1 versus 13.8%) and freedom from biopsy proven rejection (78.4 versus 66.1%) were observed between TAC/DAC and TAC/STR. Patient survival estimates were significantly lower with TAC/DAC than with TAC/STR (83.1 versus 95.5%; 95% CI, -0.227 to -0.019%), and graft survival was numerically lower (80.1 versus 91.1%, P = NS). Completion rates (45 versus 82%) indicated poorer tolerability with TAC/DAC than with TAC/STR. Steroid-free immunosuppression had no real impact on HCV viral load. HCV recurrence was higher with TAC/STR. Results are inconclusive due to the unexpected lower completion rates in the TAC/DAC arm.
Are we ready for the use of foxp3(+) regulatory T cells for immunodiagnosis and immunotherapy in kidney transplantation?
Salcido-Ochoa F, Yusof N, Hue SS … +3 more , Haase D, Kee T, Rotzschke O
J Transplant · 2012 · PMID 22690325 · Full text
The existence of T-cell subsets naturally committed to perform immunoregulation has led to enthusiastic efforts to investigate their role in the immunopathogenesis of transplantation. Being able to modulate alloresponses...
The existence of T-cell subsets naturally committed to perform immunoregulation has led to enthusiastic efforts to investigate their role in the immunopathogenesis of transplantation. Being able to modulate alloresponses, regulatory T cells could be used as an immunodiagnostic tool in clinical kidney transplantation. Thus, the measurement of Foxp3 transcripts, the presence of regulatory T cells in kidney biopsies, and the phenotypic characterisation of the T-cell infiltrate could aid in the diagnosis of rejection and the immune monitoring and prediction of outcomes in kidney transplantation. Interestingly, the adoptive transfer of regulatory T cells in animal models has been proven to downmodulate powerful alloresponses, igniting translational research on their potential use as an immunomodulatory therapy. For busy transplant clinicians, the vast amount of information in the literature on regulatory T cells can be overwhelming. This paper aims to highlight the most applicable research findings on the use of regulatory T cells in the immune diagnosis and potential immunomodulatory therapy of kidney transplant patients. However, can we yet rely on differential regulatory T-cell profiles for the identification of rejection or to tailor patient's immunosuppression? Are we ready to administer regulatory T cells as inductive or adjunctive therapy for kidney transplantation?
Perioperative Minimal Induction Therapy: A Further Step toward More Effective Immunosuppression in Transplantation.
Gennarini A, Cravedi P, Marasà M … +6 more , Perna A, Rota G, Bontempelli M, Sandrini S, Remuzzi G, Ruggenenti P
J Transplant · 2012 · PMID 22685630 · Full text
Dual induction with low doses of rabbit anti-human thymoglobulin (RATG) and basiliximab effectively and safely prevented allograft rejection in high-risk renal transplant recipients. To assess whether treatment timing af...
Dual induction with low doses of rabbit anti-human thymoglobulin (RATG) and basiliximab effectively and safely prevented allograft rejection in high-risk renal transplant recipients. To assess whether treatment timing affects efficacy and tolerability, in this single-center, matched-cohort study, we compared posttransplant outcomes in 25 patients and 50 gender-, age-, and treatment-matched reference patients induced with the same course of 7 daily RATG infusions (0.5 mg/kg/day) started before or after engraftment, respectively. All subjects received basiliximab (20 mg) before and 4 days after transplantation, withdrew steroids within 6 days after surgery, and were maintained on steroid-free immunosuppression with cyclosporine and mycophenolate mofetil or azathioprine. Over 12 months after transplant, 1 patient (4%) and 13 reference patients (26%) had acute rejection episodes. One patient and 5 reference-patients required dialysis therapy because of delayed graft function. In all patients circulating CD4+ and CD8+ T lymphocytes were fully depleted before engraftment. Both treatments were well tolerated. In kidney transplantation, perioperative RATG infusion enhances the protective effect of low-dose RATG and basiliximab induction against graft rejection and delayed function, possibly because of more effective inhibition of early interactions between circulating T cells and graft antigens.
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