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Graft Function (graft + function)
Kinds of Graft Function Selected AbstractsA Risk Prediction Model for Delayed Graft Function in the Current Era of Deceased Donor Renal TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010W. D. Irish Delayed graft function (DGF) impacts short- and long-term outcomes. We present a model for predicting DGF after renal transplantation. A multivariable logistic regression analysis of 24 337 deceased donor renal transplant recipients (2003,2006) was performed. We developed a nomogram, depicting relative contribution of risk factors, and a novel web-based calculator (http://www.transplantcalculator.com/DGF) as an easily accessible tool for predicting DGF. Risk factors in the modern era were compared with their relative impact in an earlier era (1995,1998). Although the impact of many risk factors remained similar over time, weight of immunological factors attenuated, while impact of donor renal function increased by 2-fold. This may reflect advances in immunosuppression and increased utilization of kidneys from expanded criteria donors (ECDs) in the modern era. The most significant factors associated with DGF were cold ischemia time, donor creatinine, body mass index, donation after cardiac death and donor age. In addition to predicting DGF, the model predicted graft failure. A 25,50% probability of DGF was associated with a 50% increased risk of graft failure relative to a DGF risk <25%, whereas a >50% DGF risk was associated with a 2-fold increased risk of graft failure. This tool is useful for predicting DGF and long-term outcomes at the time of transplant. [source] High Dose Epoetin Beta in the First Weeks Following Renal Transplantation and Delayed Graft Function: Results of the Neo-PDGF StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010F. Martinez Erythropoietin promotes nephroprotection in animal models of ischemia-reperfusion injury. Neorecormon® and Prevention of Delayed Graft Function (Neo-PDGF) is a French open-label multicenter randomized study to evaluate the effect of high doses of epoetin beta (EPO-,) during the first 2 weeks of renal transplantation on renal function in patients at risk for delayed graft function (DGF). One hundred and four patients were included in the study. Patients randomized in treatment group (A) received four injections of EPO-, (30.000 UI each), given before surgery and at 12 h, 7 days and 14 days posttransplantation. Patients randomized in control group (B) did not receive EPO-,. Immunosuppression included induction with basiliximab and maintenance therapy with steroids, mycophenolate mofetil and tacrolimus. At 1 month posttransplant, the estimated glomerular filtration rate (MDRD formula) was 42.5 ± 19.0 mL/min in the EPO-, group and 44.0 ± 16.3 mL/min in the control group (p = ns). The frequency of DGF was similar in both groups (32% vs. 38.8%; p = ns). No difference in the incidence of serious adverse events was observed. (ClinicalTrials.gov number, NCT00815867.) [source] Extracorporeal Support: Improves Donor Renal Graft Function After Cardiac DeathAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010A. Rojas-Pena Donors after cardiac death (DCD) could increase the organ pool. Data supports good long-term renal graft survival. However, DCDs are <10% of deceased donors in the United States, due to delayed graft function, and primary nonfunction. These complications are minimized by extracorporeal support after cardiac death (ECS-DCD). This study assesses immediate and acute renal function from different donor types. DCDs kidneys were recovered by conventional rapid recovery or by ECS, and transplanted into nephrectomized healthy swine. Warm ischemia of 10 and 30 min were evaluated. Swine living donors were controls (LVD). ECS-DCDs were treated with 90 min of perfusion until organ recovery. After procurement, kidneys were cold storage 4,6 h. Renal vascular resistance (RVR), urine output (UO), urine protein concentration (UrPr) and creatinine clearance (CrCl), were collected during 4 h posttransplantation. All grafts functioned with adequate renal blood flow for 4 h. RVR at 4 h posttransplant returned to baseline only in the LVD group (0.36 mmHg/mL/min ± 0.03). RVR was higher in all DCDs (0.66 mmHg/mL/min ± 0.13), without differences between them. UO was >50 mL/h in all DCDs, except in DCD-30 (6.8 mL/h ± 1.7). DCD-30 had lower CrCl (0.9 mL/min ± 0.2) and higher UrPr >200 mg/dL, compared to other DCDs >10 mL/min and <160 mg/dL, respectively. Normothermic ECS can resuscitate kidneys to transplantable status after 30 min of cardiac arrest/WI. [source] Diabetes Mellitus: A Risk Factor for Delayed Graft Function after Deceased Donor Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010J. Parekh Early graft function is a major determinant of long-term outcomes after renal transplantation. Recently, recipient diabetes was identified as a risk factor for poor initial graft function in living donor renal transplantation. To further explore this association, we performed a paired analysis of deceased donor renal transplants from January 1994 to December 2005. A total of 25,523 transplant pairs were analyzed via conditional logistic regression. Diabetic recipients were older (53.16 vs. 46.75 years, p < 0.01), had a lower average panel reactive antibody (12% vs. 15%, p < 0.01) and fewer prior transplants (0.07 vs. 0.12, p < 0.01). Recipient diabetes, age, male gender, African American race, elevated peak panel reactive antibody and increased cold ischemia time were independent risk factors for delayed graft function. Specifically, diabetic recipients had increased risk of DGF on univariate analysis (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.23,1.42, p < 0.01). Multivariable analysis confirmed this association but the risk differed by recipient gender; with diabetes having a greater effect in women (OR 1.66, 95% CI 1.45,1.91, p < 0.01) compared to men (OR 1.28, 95% CI 1.15,1.43, p < 0.01). It is unknown whether the deleterious impact of recipient diabetes on graft function after renal transplantation results from perioperative hyperglycemia or the chronic sequelae of diabetes. [source] High Weight Differences between Donor and Recipient Affect Early Kidney Graft Function,A Role for Enhanced IL-6 SignalingAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009W. Gong The frequency of delayed function of kidney transplants varies greatly and is associated with quality of graft, donor age and the duration of cold ischemia time. Furthermore, body weight differences between donor and recipient can affect primary graft function, but the underlying mechanism is poorly understood. We transplanted kidney grafts from commensurate body weight (L-WD) or reduced body weight (H-WD) donor rats into syngeneic or allogeneic recipients. Twenty-four hours posttransplantation, serum creatinine levels in H-WD recipients were significantly higher compared to L-WD recipients indicating impaired primary graft function. This was accompanied by upregulation of IL-6 transcription and increased tubular destruction in grafts from H-WD recipients. Using DNA microarray analysis, we detected decreased expression of genes associated with kidney function and an upregulation of other genes such as Cyp3a13, FosL and Trib3. A single application of IL-6 into L-WD recipients is sufficient to impair primary graft function and cause tubular damage, whereas immediate neutralization of IL-6 receptor signaling in H-WD recipients rescued primary graft function with well-preserved kidney graft architecture and a normalized gene expression profile. These findings have strong clinical implication as anti-IL6R treatment of patients receiving grafts from lower-weight donors could be used to improve primary graft function. [source] Fate of the Mate: The Influence of Delayed Graft Function in Renal Transplantation on the Mate RecipientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009J. F. Johnson Delayed graft function (DGF) in a deceased-donor renal recipient is associated with allograft dysfunction 1-year posttransplant. There is limited research about the influence to allograft function on the mate of a DGF recipient over time. Using a retrospective cohort design, we studied 55 recipients from a single center. The primary outcome was the change in glomerular filtration rate (GFR) 1-year posttransplant. The secondary outcome was the GFR at baseline. We found that mates to DGF recipients had a mean change in GFR 1-year posttransplant of ,11.2 mL/min, while the control group had a mean change of ,0.4 mL/min. The difference in the primary outcome was significant (p = 0.025) in a multivariate analysis, adjusting for cold ischemic time, panel reactive antibody level, allograft loss, human leukocyte antibody (HLA)-B mismatches and HLA-DR mismatches. No significant difference between groups was found in baseline GFR. In conclusion, mates to DGF recipients had a significantly larger decline in allograft function 1-year posttransplant compared to controls with similar renal function at baseline. We believe strategies that may preserve allograft function in these,at-risk'recipients should be developed and tested. [source] 2202 Kidney Transplant Recipients with 10 Years of Graft Function: What Happens Next?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2008A. J. Matas The ultimate goal of clinical transplantation is for the recipients to achieve long-term survival, with continuing graft function, that is equivalent to that of the age-matched general population. We studied subsequent outcome in kidney transplant recipients with 10 years of graft function. In all, 2202 kidney transplant recipients survived with graft function >10 years. For 10-year survivors, the actuarial 25-year patient survival rate for primary transplant living donor (LD) recipients was 57%; graft survival, 43%. For primary transplant deceased donor (DD) recipients, the actuarial 25-year patient survival rate was 39%; graft survival, 27%. The two major causes of late graft loss were death (with graft function) and chronic allograft nephropathy (tubular atrophy and interstitial fibrosis). The two major causes of death with function were cardiovascular disease (CVD) and malignancy. For nondiabetic recipients, the mean age at death with function from CVD was 54 ± 13 years; for diabetic recipients, 53 ± 7 years. By 20 years posttransplant, morbidity was common: >40% recipients had skin cancer (mean age for nondiabetic recipients, 53 ± 13 years; for diabetics, 49 ± 8 years), >10% had non-skin cancer (mean age for nondiabetic recipients, 53 ± 16 years; for diabetics, 46 ± 9 years), and >30% had CVD (mean age for nondiabetic recipients, 53 ± 15 years; for diabetics, 47 ± 9 years). We conclude that long-term transplant recipients have a high rate of morbidity and early mortality. As short-term results have improved, more focus is needed on long-term outcome. [source] The Transcriptome of the Implant Biopsy Identifies Donor Kidneys at Increased Risk of Delayed Graft FunctionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2008T. F. Mueller Improved assessment of donor organ quality at time of transplantation would help in management of potentially usable organs. The transcriptome might correlate with risk of delayed graft function (DGF) better than conventional risk factors. Microarray results of 87 consecutive implantation biopsies taken postreperfusion in 42 deceased (DD) and 45 living (LD) donor kidneys were compared to clinical and histopathology-based scores. Unsupervised analysis separated the 87 kidneys into three groups: LD, DD1 and DD2. Kidneys in DD2 had a greater incidence of DGF (38.1 vs. 9.5%, p < 0.05) than those in DD1. Clinical and histopathological risk scores did not discriminate DD1 from DD2. A total of 1051 transcripts were differentially expressed between DD1 and DD2, but no transcripts separated DGF from immediate graft function (adjusted p < 0.01). Principal components analysis revealed a continuum from LD to DD1 to DD2, i.e. from best to poorest functioning kidneys. Within DD kidneys, the odds ratio for DGF was significantly increased with a transcriptome-based score and recipient age (p < 0.03) but not with clinical or histopathologic scores. The transcriptome reflects kidney quality and susceptibility to DGF better than available clinical and histopathological scoring systems. [source] Is Anemia a Predictor for Mortality and Loss of Graft Function in Kidney Transplant Recipients?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2007M. R. Weir The relationship of anemia to outcomes in kidney transplantation may not be the same as chronic kidney disease, and should be established in renal transplant population studies. See also article by Molnar et al in this issue on page 818. [source] Delayed Graft Function: Utility of Predictive ModelsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2006C. Kubal No abstract is available for this article. [source] Urine NGAL and IL-18 are Predictive Biomarkers for Delayed Graft Function Following Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2006C. R. Parikh Delayed graft function (DGF) due to tubule cell injury frequently complicates deceased donor kidney transplants. We tested whether urinary neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) represent early biomarkers for DGF (defined as dialysis requirement within the first week after transplantation). Urine samples collected on day 0 from recipients of living donor kidneys (n = 23), deceased donor kidneys with prompt graft function (n = 20) and deceased donor kidneys with DGF (n = 10) were analyzed in a double blind fashion by ELISA for NGAL and IL-18. In patients with DGF, peak postoperative serum creatinine requiring dialysis typically occurred 2,4 days after transplant. Urine NGAL and IL-18 values were significantly different in the three groups on day 0, with maximally elevated levels noted in the DGF group (p < 0.0001). The receiver,operating characteristic curve for prediction of DGF based on urine NGAL or IL-18 at day 0 showed an area under the curve of 0.9 for both biomarkers. By multivariate analysis, both urine NGAL and IL-18 on day 0 predicted the trend in serum creatinine in the posttransplant period after adjusting for effects of age, gender, race, urine output and cold ischemia time (p < 0.01). Our results indicate that urine NGAL and IL-18 represent early, predictive biomarkers of DGF. [source] Outcome of Nonheart-Beating Donor Kidneys with Prolonged Delayed Graft Function after TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2005Jeroen J. M. Renkens Nonheart-beating donor (NHBD) kidneys are frequently associated with delayed graft function (DGF), with a deleterious effect on kidney function and allograft survival. The influence and the duration of DGF on the outcome of NHBD kidneys are assessed. All recipients of an NHBD kidney in the period 1993,2003 were reviewed. Excluded from analysis were patients with primary nonfunction (PNF). One hundred and five patients with a functioning NHBD graft were reviewed: 23 (22%) had immediate function (group 1), 40 (38%) had DGF , 2 weeks (group 2), 31 (30%) had DGF 15 days to 4 weeks (group 3) and 11 (10%) had DGF for >4 weeks (group 4). Creatinine clearance at 3 months was higher in groups 1 and 2 versus group 4 (p = 0.015 and p = 0.006, respectively) and was higher in group 2 versus group 4, at 1 year (p = 0.01). Graft survival was 95%, 98%, 97% and 89%, respectively, at 1 year and 95%, 85%, 77% and 89%, respectively, at 5 years, which was not significantly different. The duration of DGF in NHB kidneys has a negative effect on creatinine clearance, but no effect on graft survival. [source] Polyomavirus Allograft Nephropathy: Sequential Assessment of Histologic Viral Load, Tubulitis, and Graft Function Following Changes in ImmunosuppressionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2003Betul Celik Our initial cases of polyoma virus allograft nephropathy (PVAN) received pulse steroids due to anxiety about concomitant acute rejection triggered by the presence of tubulitis. However, our current policy is to reduce immunosuppression in all cases. The aim of this study was to determine whether clinical follow-up in these patient categories shows any differences in: (a) histologic viral load, (b) grade of tubulitis, and (c) graft function. Reduced viral load assessed within 8 weeks was seen in 4/20 (20.0%) biopsies treated initially by increased immunosuppression, compared to 15/19 (83.3%) biopsies treated with reduced immunosuppression (p = 0.001, Fisher's exact test). Yet, >70% reversal of the rise in serum creatinine occurred in only 3/19 (15.8%) and 1/19 (5.3%) patients, respectively, in these two groups. Improved tubulitis was seen in 11/20 (55%) of biopsies treated with steroids, despite the lack of beneficial effect on serum creatinine in 12/19 (63.1%) instances. In biopsies not treated with any change in immunosuppression, the serum creatinine remained stable in 1/5 (20%) and worsened in 4/5 (80%) biopsies. These data demonstrate that in biopsies with PVAN and tubulitis, reduced immunosuppression is more effective in lowering viral load than steroid therapy. Lack of parallelism between viral load, tubulitis grade, and serum creatinine illustrates a complex interplay of viral and alloimmune factors leading to graft injury. [source] Laparoscopic (vs. Open) Live Donor Nephrectomy: A UNOS Database Analysis of Early Graft Function and SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2003Christoph Troppmann The impact of laparoscopic (lap) live donor nephrectomy on early graft function and survival remains controversial. We compared 2734 kidney transplants (tx) from lap donors and 2576 tx from open donors reported to the U.S. United Network for Organ Sharing from 11/1999 to 12/2000. Early function quality (>40 mL urine and/or serum creatinine [creat] decline >25% during the first 24 h post-tx) and delayed function incidence were similar for both groups. Significantly more lap (vs. open) txs, however, had discharge creats greater than 1.4 mg/dL (49.2% vs. 44.9%, p = 0.002) and 2.0 mg/dL (21.8% vs. 19.5%, p = 0.04). But all later creats, early and late rejection, as well as graft survival at 1 year (94.4%, lap tx vs. 94.1%, open tx) were similar for lap and open recipients. Our data suggests that lap nephrectomy is associated with slower early graft function. Rejection rates and short-term graft survival, however, were similar for lap and open graft recipients. Further prospective studies with longer follow up are necessary to assess the potential impact of the laparoscopic procurement mode on early graft function and long-term outcome. [source] Electroporation-mediated interleukin-10 overexpression in skeletal muscle reduces acute rejection in rat cardiac allograftsTHE JOURNAL OF GENE MEDICINE, Issue 2 2006Reza Tavakoli Abstract Objectives Human interleukin 10 (hIL-10) may reduce acute rejection after organ transplantation. Our previous data shows that electroporation-mediated transfer of plasmid DNA to peripheral muscle enhances gene transduction dramatically. This study was designed to investigate the effect of electroporation-mediated overexpression of hIL-10 on acute rejection of cardiac allografts in the rat. Methods The study was designed to evaluate the effect of hIL-10 gene transfer on (a) early rejection pattern and (b) graft survival. Gene transfer was achieved by intramuscular (i.m.) injection into the tibialis anterior muscle of Fischer (F344) male recipients followed by electroporation 24 h prior to transplantation. Heterotopic cardiac transplantation was performed from male Brown Norway rat to F344. Four groups were studied (n = 6). Treated animals in groups B1 and B2 received 2.5 µg of pCIK hIL-10 and control animals in groups A1 and A2 distilled water. Graft function was assessed by daily palpation. Animals from group A1 were sacrificed at the cessation of the heart beat of the graft and those in group B1 were sacrificed at day 7; blood was taken for ELISA measurement of hIL-10 and tissue for myeloperoxidase (MPO) measurement and histological assessment. To evaluate graft survival, groups A2 and B2 were sacrificed at cessation of the heart beat of the graft. Results Histological examination revealed severe rejection (IIIB-IV) in group A1 in contrast to low to moderate rejection (IA-IIIA) in group B1 (p = 0.02). MPO activity was significantly lower in group B1 compared to group A1 (18 ± 7 vs. 32 ± 14 mU/mg protein, p = 0.05). Serum hIL-10 levels were 46 ± 13 pg/ml in group B1 vs. 0 pg/ml in group A1. At day 7 all heart allografts in the treated groups B1 and B2 were beating, whereas they stopped beating at 5 ± 2 days in groups A1 and A2 vs. 14 ± 2 days in group B2 (p = 0.0012). Conclusions Electroporation-mediated intramuscular overexpression of hIL-10 reduces acute rejection and improves survival of heterotopic heart allografts in rats. This study demonstrates that peripheral overexpression of specific genes in skeletal muscle may reduce acute rejection after whole organ transplantation. Copyright © 2006 John Wiley & Sons, Ltd. [source] Brief Communication: Successful Isolated Liver Transplantation in a Child with Atypical Hemolytic Uremic Syndrome and a Mutation in Complement Factor HAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010W. Haller A male infant was diagnosed with atypical hemolytic uremic syndrome (aHUS) at the age of 5.5 months. Sequencing of the gene (CFH) encoding complement factor H revealed a heterozygous mutation (c.3644G>A, p.Arg1215Gln). Despite maintenance plasmapheresis he developed recurrent episodes of aHUS and vascular access complications while maintaining stable renal function. At the age of 5 years he received an isolated split liver graft following a previously established protocol using pretransplant plasma exchange (PE) and intratransplant plasma infusion. Graft function, renal function and disease remission are preserved 2 years after transplantation. Preemptive liver transplantation prior to the development of end stage renal disease is a valuable option in the management of aHUS associated with CFH mutations. [source] Successful Urgent Transplantation of an Adult Kidney into a Child with Inferior Vena Cava ThrombosisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009R. B. Stevens Poor venous drainage options following inferior vena cava (IVC) thrombosis have been considered to complicate or preclude renal transplantation of adult kidneys into pediatric patients. We describe urgent renal transplantation in a 5-year-old (15.3 kg) male with IVC thrombosis using an adult living donor. Preoperative magnetic resonance venography revealed a patent infrahepatic/suprarenal vena cava and portal system. In surgery, the right liver lobe was mobilized sufficiently to anastomose the graft renal vein to the native IVC at the confluence of the native left renal vein and proximal vena cava. Graft function has remained excellent with serum creatinine of 0.5 mg/dL at 36 months. IVC thrombosis need not preclude successful transplantation of adult-sized kidneys into children. [source] Lymphatic Neoangiogenesis in Human Renal Allografts: Results from Sequential Protocol BiopsiesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2007S. Stuht Neoangiogenesis of lymphatic vessels may be important for the cellular immune response in renal transplants. To determine the prevalence and chronology of lymph vessel proliferation and its relation to cellular infiltrates and allograft function, we analyzed sequential protocol biopsies (n = 162), taken at 6, 12 and 26 weeks after transplantation. Biopsies were stained with an antibody against podoplanin and lymphatic vessel density was quantified per square millimeter. The prevalence of lymph vessel-positive biopsies and the lymph vessel density were similar at 6, 12 and 26 weeks after transplantation. Biopsies with acute cellular rejection showed no significantly different lymph vessel density compared to those below the threshold for acute rejection or chronic allograft nephropathy. While lymphatic neoangiogenesis was equally prevalent in biopsies with and without infiltrates, the lymph vessel density was significantly higher in areas with cellular infiltrates than in areas without. Graft function at 1 year after transplantation was better in cases with lymph vessels in their infiltrates compared to cases with lymph vessel-free infiltrates. In conclusion, lymphangiogenesis not only shows a clear association with cellular infiltrates but might also have an impact on the pathogenicity of these cellular infiltrates. [source] Hand-Assisted Laparoscopic Living-Donor Nephrectomy as an Alternative to Traditional Laparoscopic Living-Donor NephrectomyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2002Joseph F. Buell The benefits of laparoscopic living-donor nephrectomy (LDN) are well described, while similar data on hand-assisted laparoscopic living-donor nephrectomy (HALDN) are lacking. We compare hand-assisted laparoscopic living-donor nephrectomy with open donor nephrectomy. One hundred consecutive hand-assisted laparoscopic living-donor nephrectomy (10/98,8/01) donor/recipient pairs were compared to 50 open donor nephrectomy pairs (8/97, 1/00). Mean donor weights were similar (179.6 ± 40.8 vs. 167.4 ± 30.3 lb; p =,NS), while donor age was greater among hand-assisted laparoscopic living-donor nephrectomy (38.2 ± 9.5 vs. 31.2 ± 7.8 year; p <,0.01). Right nephrectomies was fewer in hand-assisted laparoscopic living-donor nephrectomy [17/100 (17%) vs. 22/50 (44%); p <,0.05]. Operative time for hand-assisted laparoscopic living-donor nephrectomy (3.9 ± 0.7 vs. 2.9 ± 0.5 h; p <,0.01) was longer; however, return to diet (6.9 ± 2.8 vs. 25.6 ± 6.1 h; p <,0.01), narcotics requirement (17.9 ± 6.3 vs. 56.3 ± 6.4 h; p <,0.01) and length of stay (51.7 ± 22.2 vs. 129.6 ± 65.7 h; p <,0.01) were less than open donor nephrectomy. Costs were similar ($11 072 vs. 10 840). Graft function and 1-week Cr of 1.4 ± 0.9 vs. 1.6 ± 1.1 g/dL (p =,NS) were similar. With the introduction of HALDN, our laparoscopic living-donor nephrectomy program has increased by 20%. Thus, similar to traditional laparoscopic donor nephrectomy, hand-assisted laparoscopic living-donor nephrectomy provides advantages over open donor nephrectomy without increasing costs. [source] Efficacy and safety of preemptive anti-CMV therapy with valganciclovir after kidney transplantationCLINICAL TRANSPLANTATION, Issue 1 2007Kai Lopau Abstract:, Background:, CMV infections still pose a potentially serious threat to kidney transplant recipients and have a significant impact on graft as well as patient survival. The antiviral agent valganciclovir (VGCV) has a greater bioavailability after oral administration than oral ganciclovir (GCV) and can be considered a substitute for GCV. The substance is approved in North America and Europe for anti-CMV prophylaxis after organ transplantation. In this pilot study, we examined if VGCV could also be administered in preemptive treatment of CMV infections. Methods:, Twenty-eight renal transplant recipients suffering from 32 asymptomatic episodes of CMV infection were treated with VGCV and followed up. CMV infection was diagnosed by routine controls of pp65-antigenemia in pre-defined intervals. All patients received sequential quadruple immunosuppression. VGCV was given for up to 12 wk in a dosage adapted to renal graft function. Efficacy and safety parameters were monitored for 16 wk. Results:, Twenty-seven episodes of CMV antigenemia, two patients progressing to CMV syndrome and three patients progressing to CMV disease were treated. Primary efficiency was 79%, Four patients relapsed and were treated with a second course resulting in serological recovery. Two patients did not respond to oral VCGV and were switched to another antiviral agent. Graft function remained stable during and after treatment. Serious side effects were seen in seven patients, four patients complained of diarrhea and gastrointestinal pain, three patients suffered from leucopenia, in one of these treatment had to be temporary paused. Fifty-nine percent of all episodes were treated in a completely ambulatory setting. Conclusions:, VGCV can be considered as an option also for preemptive treatment of CMV infections after renal transplantation. The antiviral potency seems to be adequate, potential side effects are comparable with IV GCV. Because of the improved pharmacokinetics of VGCV the substance can be used to abbreviate or even completely avoid in-hospital care of CMV infections. [source] Cryopreservation of vascularized ovary: An evaluation of histology and function in ratsMICROSURGERY, Issue 5 2008Shijie Qi M.D. Cryopreservation of organs has been investigated to sustain the reproductive function of patients undergoing sterilizing chemotherapy and radiotherapy or reproductive surgery. A modified protocol for whole organ cryopreservation was described and the outcome of cryopreservative ovaries was evaluated, and apoptosis of cryopreservative cells stored for different time period and the viability of cryopreserved cells stored at different temperature was examined in rats. Lewis rat ovarian grafts were perfused for 30 min at 0.35 ml/min with M2 medium containing 0.1M fructose and increasing concentrations of 0,1.5M dimethylsulfoxide, cooled to ,140°C controlled by a computerized program, and stored in liquid nitrogen (,196°C) for 24 hours. After being thawed, ovaries were transplanted to syngeneic recipients after bilateral oophorectomy. Graft functions were monitored postoperatively. The major findings were that: 1) A 100% survival rate of rat ovaries was achieved in this study. Ovarian hormone secretion recovered in 80% rats which had received cryopreservative ovarian grafts. Postoperative serum estradiol levels in the cryopreservative graft group were lower than in the sham surgery control, but much higher than in the bilateral oophorectomy group. 2) Histological examination of cryopreservative ovarian grafts showed preantral and antral follicles. Two gestations were obtained. 3) Estradiol levels remained low in ovariectomized rats while in the oophorectomized rats given cryopreservative ovarian grafts levels started to rise after 14 ± 3 days. 4) The average viability in the cells from cryopreservative ovary organ (,196°C) was about 71 ± 18% compared to 90 ± 9% of fresh cells. This success should encourage further improvement of cryopreservative techniques for large organs. © 2008 Wiley-Liss, Inc. Microsurgery, 2008. [source] Gene delivery of Cu/Zn-superoxide dismutase improves graft function after transplantation of fatty livers in the ratHEPATOLOGY, Issue 6 2000Thorsten G. Lehmann Oxygen-derived free radicals play a central role in reperfusion injury after organ transplantation, and fatty livers are particularly susceptible. Endogenous radical scavengers such as superoxide dismutase (SOD) degrade these radicals; however, SOD is destroyed rapidly when given exogenously. Therefore, an adenoviral vector encoding the Cu/Zn-SOD gene (Ad.SOD1) was used here to test the hypothesis that organ injury would be reduced and survival increased in a rat model of transplantation of fatty livers. Donors received chow diet (untreated), high-fat diet, or ethanol-containing high-fat diet. Some of the ethanol-fed donors were infected either with the gene lacZ encoding bacterial ,-galactosidase (Ad.lacZ), or Ad.SOD1. After liver transplantation, SOD activity and protein expression in liver, survival, histopathology, release of transaminases, free radical adducts in bile, and activation of NF-,B, I,B kinase (IKK), Jun-N-terminal kinase (JNK), and TNF, were evaluated. Ad.SOD1 treatment increased survival dramatically, blunted transaminase release, and reduced necrosis and apoptosis significantly. Free radical adducts were increased two-fold in the ethanol group compared with untreated controls. Ad.SOD1 blunted this increase and reduced the activation of NF-,B. However, release of TNF, was not affected. Ad.SOD1 also blunted JNK activity after transplantation. This study shows that gene therapy with Ad.SOD1 protects marginal livers from failure after transplantation because of decreased oxygen radical production. Genetic modification of fatty livers using viral vectors represents a new approach to protect marginal grafts against primary nonfunction. [source] Recurrence of primary biliary cirrhosis and primary sclerosing cholangitis after liver transplantation in JapanHEPATOLOGY RESEARCH, Issue 2007Satoshi Yamagiwa Although there was some initial controversy, there is now a consensus that primary biliary cirrhosis (PBC) does indeed recur in both cadaveric and living donated allografts. Recurrence rate after deceased donor liver transplantation (LT) was reported to be 10.9,23% at 5 years. In the present study, we reviewed 221 PBC patients who underwent living-donor liver transplantation (LDLT) in Japan. The 5-year overall survival rate was 79%, and the rate of recurrence based on histological findings was 10% (7/70) after a median time of 36 months. Primary immunosuppression, withdrawal of corticosteroids and human leukocyte antigen matches were not associated with the recurrence. Recurrent PBC appears to have little impact on graft function and survival, but this may become a greater problem with longer follow up. It is noteworthy that the 10-year survival of primary sclerosing cholangitis (PSC) patients who underwent LDLT wasfound to be only 39.1% in Japan, whereas that of PBC was 72.9%. Factors associated with the poor prognosis include biliary strictures, hepatobiliary and colorectal malignancies, and recurrence of PSC. In our study, we reviewed 66 patients with PSC who underwent LDLT in Japan. The 5-year survival rate was 72%, and the rate of recurrence diagnosed on histological and cholangiographic findings was 25% (11/44). Well-defined diagnostic criteria and longer studies are required to characterize the nature of recurrent PSC and its impact on graft survival in more detail. [source] Liver transplantation for the sequelae of intra-operative bile duct injuryHPB, Issue 3 2002E De Santibañes Background Intra-operative bile duct injuries (IBDI) are potentially severe complications of the treatment of benign conditions, with unpredictable long-term results. Multiple procedures are frequently needed to correct these complications. In spite of the application of these procedures, patients with severe injuries can develop irreversible liver disease. Liver transplantation (LT) is currently the only treatment available for such patients, but little information has been published concerning the results of LT. Methods Eight patients with LT for end-stage liver disease for IBDI were studied retrospectively. They had failure of multiple previous treatments and experienced recurrent episodes of cholangitis, oesophageal variceal bleeding, severe pruritus, refractory ascites and spontaneous peritonitis. Results Mean recipient hepatectomy time was of 243 minutes (range 140,295 min), the complete procedure averages 545 minutes (260,720) and intraoperative red-blood-cells consumption was 6.5 units (1,7). One patient required reoperation due to perforation of a Roux-en-Y loop, and three developed minor complications (2 wound infections, 1 inguinal lymphocele). One patient died due to nosocomial pneumonia (mortality rate 12.5%). One patient required retransplantation due to delayed hepatic artery thrombosis. At follow-up 75% of patients are alive with normal graft function and an excellent quality of life. Conclusions LT represents a safe curative treatment for end-stage liver disease after IBDI, albeit a major undertaking in the context of a surgical complication in the treatment of benign disease. The complications of the surgical procedure and the long-standing immunosupression impart a high cost for resolutions of these sequelae but LT represents the only long-term effective treatment for these selected patients. [source] Clinical islet transplant: current and future directions towards toleranceIMMUNOLOGICAL REVIEWS, Issue 1 2003A. M. James Shapiro Summary:, The ultimate goal of islet transplantation is to completely correct the diabetic state from an unlimited donor source, without the need for chronic immunosuppressive drug therapy. Although islet transplantation provides an opportunity to develop innovative strategies for tolerance in the clinic, both alloimmune and autoimmune barriers must be controlled, if stable graft function is to be maintained long-term. After islet extraction from the pancreas, the cellular graft may be stored in tissue culture or cryopreserved for banking, providing an opportunity not only to optimally condition the recipient but also to allow in vitro immunologic manipulation of the graft before transplantation, unlike solid organ grafts. As such, islets may be considered a ,special case.' Remarkable progress has occurred in the last three years, with dramatic improvements in outcomes after clinical islet transplantation. The introduction of a steroid-free, sirolimus-based, anti-rejection protocol and islets prepared from two (or rarely three) donors led to high rates of insulin independence. The ,Edmonton Protocol' has been successfully replicated by other centers in an international multicenter trial. A number of key refinements in pancreas transportation, processing, purification on non-ficoll-based media, storage of islets in culture for two days and newer immunological conditioning and induction therapies have led to continued advancement through extensive collaboration between key centers. This review outlines the historical development of islet transplantation over the past 30 years, provides an update on current clinical outcomes, and summarizes a series of unique opportunities for development and early testing of tolerance protocols in patients. [source] BK virus nephropathy: Clinical experience in a university hospital in JapanINTERNATIONAL JOURNAL OF UROLOGY, Issue 12 2009Tatsuya Takayama Objectives: To review the medical records of patients with BK virus nephropathy (BKVN) following kidney transplantation in our institution. Methods: We screened patients for decoy cells using urine cytology, assessed serum creatinine levels, and conducted a graft biopsy, as well as assessed the presence of plasma BK virus DNA by quantitative real-time polymerase chain reaction. The treatment of BKVN was based on the decreased use of immunosuppressants. Results: Overall, six male patients were studied (mean age 40.8 years, range 18,58; mean donor age 45.2 years, range 15,67). A positive urine cytology screen led to the subsequent detection of plasma BK virus DNA in the five patients with urine cytology results positive for decoy cells. In the four patients in whom plasma BK virus DNA was detected, a maximum value of DNA of ,10 000 copies/mL was observed. Time elapsed from transplantation to BKVN diagnosis ranged from 3 to 62 months. Although the two cadaver grafts were lost, the loss was not due to any effects directly associated with BKVN. The other four grafts are still functioning with a mean creatinine level of 1.8 mg/dL. Most of the patients with BKVN were regarded as being in a state of heightened immunosuppression. BK virus transition to blood was prevented in one patient. Conclusions: Early diagnosis of BKV infection with reduction of immunosuppression may potentially counter BK viremia and retard progression of BKV nephropathy. Decoy cell screening by urine cytology as well as plasma BK virus DNA screening should be considered in addition to the required graft biopsy in kidney transplant recipients, particularly in those with impaired graft function. [source] Complete robotic-assistance during laparoscopic living donor nephrectomies: An evaluation of 38 procedures at a single siteINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2007Jacques Hubert Objective: To evaluate our initial experience with entirely robot-assisted laparoscopic live donor (RALD) nephrectomies. Methods: From January 2002 to April 2006, we carried out 38 RALD nephrectomies at our institution, using four ports (three for the robotic arms and one for the assistant). The collateral veins were ligated, and the renal arteries and veins clipped, after completion of ureteral and renal dissection. The kidney was removed via a suprapubic Pfannenstiel incision. A complementary running suture was carried out on the arterial stump to secure the hemostasis. Results: Mean donor age was 43 years. All nephrectomies were carried out entirely laparoscopically, without complications and with minimal blood loss. Mean surgery time was 181 min. Average warm ischemia and cold ischemia times were 5.84 min and 180 min, respectively. Average donor hospital stay was 5.5 days. None of the transplant recipients had delayed graft function. Conclusions: Robot-assisted laparoscopic live donor nephrectomy can be safely carried out. Robotics enhances the laparoscopist's skills, enables the surgeon to dissect meticulously and to prevent problematic bleeding more easily. Donor morbidity and hospitalization are reduced by the laparoscopic approach and the use of robotics allows the surgeon to work under better ergonomic conditions. [source] Plasmapheresis as rescue therapy in accelerated acute humoral rejection,JOURNAL OF CLINICAL APHERESIS, Issue 3 2003Kottarathil A. Abraham Abstract Accelerated acute humoral rejection (AHR) continues to occur in renal transplantation despite improved crossmatching, with potentially devastating consequences. Between 1 June 1998 and 31 December 2000, 440 renal transplants were performed in our center. AHR was diagnosed by the demonstration of typical pathological features on renal histology and positive direct immunofluorescence or detection of anti-HLA antibodies in serum. AHR developed in 20 (4.5%) of our renal transplant recipients, nine male and eleven female at an average of 16.3 days post transplantation. All of these patients had a negative current cytotoxic crossmatch prior to transplantation. The median serum creatinine at diagnosis was 5.96 mg/dL, and 83% of these individuals developed oliguric renal failure requiring dialysis after having initially attained good graft function (median of best serum creatinine before AHR was 2.64 mg/dL). The 18 recipients who had not infarcted their grafts at the time of diagnosis of AHR received plasmapheresis in conjunction with intensification of their immunosuppressive regimen. This regimen was successful in reversing AHR in 78% of those treated with apheresis. In the 14 responders, graft survival at 6 months was 100% and at 12 months was 91%. Median serum creatinine at 6 and 12 months was 1.26 and 1.33 mg/dL, respectively. Patients received an average of 8.1 plasma exchanges. However, responders received a significantly higher frequency of plasmapheresis (P = .0053), despite undergoing a similar number of exchanges overall. Plasmapheresis appears to be an effective modality for reversing AHR and maintaining graft function. J. Clin. Apheresis 18:103,110, 2003. © 2003 Wiley-Liss, Inc. [source] Conservative management of an extensive renal graft subcapsular hematoma arising during living donor nephrectomy.JOURNAL OF CLINICAL ULTRASOUND, Issue 3 2010Role of Doppler sonographic posttransplant follow-up Abstract We report a case of subcapsular hematoma (SH) of a kidney graft arising during minimal-incision living-donor nephrectomy. SH covered at least two-thirds of the cortical surface. Capsulotomy was not done because it was deemed too risky. In the immediate postoperative period, a rapid deterioration of graft function was observed associated with Doppler sonographic evidence of graft compression. However, in the following days, spontaneous resolution of SH and progressive improvement of Doppler findings was observed, which preceded full recovery of graft function. Conservative management seemed a valid approach of this complication in this case where Doppler sonography proved essential for the follow-up. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2010 [source] The effects of immunosuppressive drugs on CD4+CD25+ regulatory T cells: a systematic review of clinical and basic researchJOURNAL OF EVIDENCE BASED MEDICINE, Issue 2 2010Chuntao Zhang Abstract Objective To review the effects of different immunosuppressive drugs on proliferation and function of regulatory T cells (Tregs). Methods We searched MEDLINE, Embase (from inception to September 2009), and the Cochrane Library (Issue 4, 2009) for clinical and basic research about the effects of various immunosuppressive drugs on Tregs. Data were extracted and methodological quality was assessed by two independent reviewers. Outcome measures for clinical research included blood Tregs levels, acute rejection episodes, and graft function. Outcomes for basic research included percentage of Tregs proliferation, function, Tregs phenotype, and evidence for possible mechanisms. We analyzed data qualitatively. Results Forty-two studies, including 19 clinical trials and 23 basic studies, were included. The immunosuppressive drugs studied were calcineurin inhibitors (CNIs), Rapa, anti-metabolism drugs, IL-2 receptor-blocking antibodies, T-cell depleting antibodies, and co-stimulation blockade antibodies. Most of the studies were on Rapa and CNIs. Eight basic studies on Rapa and CNIs showed that Rapa could promote the proliferation and function of Tregs, while CNIs could not. Five clinical trials involving a total of 158 patients showed that patients taking Rapa had higher blood concentration of Tregs than patients taking CNIs, but no difference was found in graft function (6,42 months follow-up). Conclusion There is substantial evidence that Rapa favors Tregs survival and function. However, the higher numbers of blood Tregs in patients treated with Rapa do not show any association with better graft function. Larger clinical studies with longer follow-up are needed to more thoroughly assess the efficacy of immunosuppressive drugs on Tregs, and reveal whether a relationship exists between Tregs and graft function. [source] | ||||||||||