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Long-term Graft Function (long-term + graft_function)
Selected AbstractsLong-term graft function with tacrolimus and cyclosporine in renal transplantation: Paired kidney analysisNEPHROLOGY, Issue 8 2009CHI YUEN CHEUNG SUMMARY: Aim: The first prospective, randomized trial with paired kidney analysis was conducted to compare the efficacy and safety of tacrolimus with cyclosporine-based immunosuppressive therapy in renal transplant recipients. This paper reports the long-term follow-up results of the authors' previously published study, with the main focus on graft survival and renal function. Methods: Chinese patients transplanted in our centre between June 1998 and June 2005 with their first deceased renal transplant were included. Patients were included if both kidneys were received by the authors' centre, thus allowing a paired analysis. Patients were randomized to receive triple immunosuppressive therapy with either tacrolimus or Neoral cyclosporine, concomitantly with prednisolone and azathioprine therapy. Results: Seventy-six patients received cadaveric kidneys from 38 donors. Each pair of kidneys was randomly assigned to a separate group (38 subjects/group). The mean follow-up duration was 6.1 ± 1.8 years. The mean calculated creatinine clearance was significantly higher in patients receiving tacrolimus-based therapy. The rate of biopsy-proven acute rejection was lower in the tacrolimus group (18.4% vs 42.1%, P = 0.03). The patient and graft survival were comparable in both treatment arms. Significantly fewer patients on tacrolimus-based therapy developed hypercholesterolaemia (P = 0.05). However, there was no significant difference in the development of post-transplant diabetes mellitus, hypertension, opportunistic infection and malignancy between both groups. Conclusion: Using the immunosuppressive regimen, tacrolimus-based therapy provided adequate immunosuppression with better renal function and less acute rejection, as compared with cyclosporine-based therapy. [source] Long-term outcomes in pediatric liver transplantationLIVER TRANSPLANTATION, Issue S2 2009John Bucuvalas Key Points 1. Critical clinical outcomes for pediatric liver transplantation (LT) recipients include (1) patient and graft survival, (2) complications (immune and nonimmune) of chronic immunosuppressive medications, and (3) long-term graft function. 2. Recurrence of malignancy, sepsis, and posttransplant lymphoproliferative disorder account for more than 65% of deaths occurring more than 1 year after LT. 3. Chronic rejection, late hepatic artery thrombosis, and biliary strictures account for 70% of graft loss occurring more than 1 year after LT. 4. Late histological changes in the allograft are emerging as a common problem in patients more than 5 years after LT. The pathogenesis of these findings and the impact on graft survival remain to be determined. Liver Transpl 15:S6,S11, 2009. © 2009 AASLD. [source] Increased expression of cytotoxic effector molecules: Different interpretations for steroid-based and steroid-free immunosuppressionPEDIATRIC TRANSPLANTATION, Issue 1 2003Thomas Satterwhite Abstract: Cytotoxic T lymphocyte (CTL) effector molecules have been studied as markers of acute rejection in renal allograft recipients on steroid-based immunosuppression. We hypothesized that basal CTL gene expression may vary with time post-transplantation as well as with different immunosuppression protocols (steroid-based or steroid-free). Variations in CTL gene expression may thus impact on the ability to predict acute allograft rejection. We used the non-invasive method of quantitative competitive-reverse transcription-polymerase chain reaction (QC-RT-PCR) to quantify the amounts of CTL effector molecules (granulysin, GL; perforin, P; granzyme B, GB) in serial peripheral blood lymphocyte (PBL) samples from steroid-free and steroid-based adult and pediatric renal allograft recipients. Patients on both protocols were clinically monitored by protocol biopsies at 1, 3, 6, and 12 months post-transplantation and for graft function at 1 yr post-transplantation in a separate clinical study. Steroid-free patients with stable graft function showed an increase in GL, P, and GB gene expression over time post-transplantation with the increase being seen largely by the first post-transplant month. A further increase in GL expression was noted at the end of the first post-transplant year in the absence of acute rejection, whereas GB and P levels were unchanged. At comparative time-points post-transplantation, CTL genes were found to be higher in steroid-free patients with stable graft function, compared to steroid-based recipients with either clinically stable graft function or acute rejection. This study suggests that levels of CTL gene expression, although important in a steroid-based regimen to monitor the risk of acute rejection, may not be similarly applied in patients on steroid-free immunosuppression. The early increase in levels seen in steroid-free patients appears to correlate with the total absence of steroids. As steroid-free patients seem to have a lower incidence of acute rejection and better long-term graft function at 1 yr, the early increase in CTL genes in the absence of acute rejection may suggest an early adaptive immune activation response, promoting early graft acceptance in this protocol. [source] The Detrimental Effect of Poor Early Graft Function After Laparoscopic Live Donor Nephrectomy on Graft OutcomesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2009J. M. Nogueira We undertook this study to assess the rate of poor early graft function (EGF) after laparoscopic live donor nephrectomy (lapNx) and to determine whether poor EGF is associated with diminished long-term graft survival. The study population consisted of 946 consecutive lapNx donors/recipient pairs at our center. Poor EGF was defined as receiving hemodialysis on postoperative day (POD) 1 through POD 7 (delayed graft function [DGF]) or serum creatinine , 3.0 mg/dL at POD 5 without need for hemodialysis (slow graft function [SGF]). The incidence of poor EGF was 16.3% (DGF 5.8%, SGF 10.5%), and it was stable in chronologic tertiles. Poor EGF was independently associated with worse death-censored graft survival (adjusted hazard ratio (HR) 2.15, 95% confidence interval (CI) 1.34,3.47, p = 0.001), worse overall graft survival (HR 1.62, 95% CI 1.10,2.37, p = 0.014), worse acute rejection-free survival (HR 2.75, 95% CI 1.92,3.94, p < 0.001) and worse 1-year renal function (p = 0.002). Even SGF independently predicted worse renal allograft survival (HR 2.54, 95% CI 1.44,4.44, p = 0.001). Risk factors for poor DGF included advanced donor age, high recipient BMI, sirolimus use and prolonged warm ischemia time. In conclusion, poor EGF following lapNx has a deleterious effect on long-term graft function and survival. [source] Pretransplant HLA Antibodies Are Associated with Reduced Graft Survival After Clinical Islet TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2007P. M. Campbell Despite significant improvements in islet transplantation, long-term graft function is still not optimal. It is likely that both immune and nonimmune factors are involved in the deterioration of islet function over time. Historically, the pretransplant T-cell crossmatch and antibody screening were done by anti-human globulin,complement-dependent cytotoxicity (AHG-CDC). Class II antibodies were not evaluated. In 2003, we introduced solid-phase antibody screening using flow-based beads and flow crossmatching. We were interested to know whether pretransplant human leukocyte antigen (HLA) antibodies or a positive flow crossmatch impacted islet function post-transplant. A total of 152 islet transplants was performed in 81 patients. Islet function was determined by a positive C-peptide. Results were analyzed by procedure. Class I and class II panel reactive antibody (PRA) > 15% and donor-specific antibodies (DSA) were associated with a reduced C-peptide survival (p < 0.0001 and p < 0.0001, respectively). A positive T- and or B-cell crossmatch alone was not. Pretransplant HLA antibodies detectable by flow beads are associated with reduced graft survival. This suggests that the sirolimus and low-dose tacrolimus-based immunosuppression may not control the alloimmune response in this presensitized population and individuals with a PRA > 15% may require more aggressive inductive and maintenance immunosuppression, or represent a group that may not benefit from islet transplantation. [source] Heightened Expression of the Cytotoxicity Receptor NKG2D Correlates with Acute and Chronic Nephropathy After Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2007M. Seiler The activating cytotoxicity receptor NKG2D binds to stress-regulated molecules encoded by the major histocompatibility complex class I chain-related (MIC) and UL-16-binding protein (ULBP)/retinoic acid early transcript (RAET) gene family. To assess whether acute allograft rejection leads to an induction of these inducible ligands and their receptor NKG2D, we examined the mRNA profiles in kidney transplant biopsies. Expression levels were correlated with the incidence of acute rejection (aRx) episodes and chronic allograft nephropathy (CAN) proven by histology. Whereas MICA, ULBP1/3 and RAET1-E did not display heightened gene expression, elevated levels of NKG2D mRNA could be associated with aRx (p < 0.001). Immunohistology of kidney biopsies diagnosed with aRx revealed NKG2D+ cells in tubulointerstitial areas positive for CD8+ cells. Most importantly, elevated levels of NKG2D mRNA were associated with restricted long-term graft function assessed by the glomerular filtration rate at 6, 12 and 18 months posttransplantation. Induced NKG2D mRNA expression was still observable in biopsies diagnosed with CAN (p < 0.001), demonstrating a higher sensitivity and specificity compared to CD3, granzyme B and granulysin mRNA measurement. Significant elevated levels of NKG2D mRNA could be further detected in urine sediment prior to aRx, suggesting this receptor as a new candidate marker for the diagnosis of acute and chronic allograft rejection. [source] In vivo IL-10 and TGF-, production by PBMC from long-term kidney transplant recipients with excellent graft function: a possible feedback mechanism participating in immunological stabilityCLINICAL TRANSPLANTATION, Issue 2 2004Josefina Alberú Abstract:, Background:, Interleukin-10 (IL-10) and transforming growth factor-, (TGF-,) are Th2-derived multifunctional cytokines that exhibit potent immunoregulatory and anti-inflammatory properties which might prolong graft survival. The aim of this study was to explore whether spontaneous production of IL-10 and TGF-, by blood mononuclear cells correlates with excellent long-term graft function. Methods:, A cross-sectional study was carried out in 32 kidney transplant recipients, without albuminuria, treated with azathioprine and prednisone. Spontaneous IL-10 and TGF-, were measured by enzyme-linked immunosorbent assay in supernatants from 24 h cultured unstimulated peripheral blood mononuclear cells. Both cytokines were also determined in 10 healthy kidney donors. Results:, There was no correlation between IL-10 or TGF-, with any variable tested, namely age, SCr, histocompatibility, and post-transplant follow-up. In vivo IL-10 production displayed a statistical trend to be higher in transplant recipients than in controls (362.3 ± 465, range 12.5,1929.3 pg/ml, and 189 ± 170, range 4.17,485.7 pg/ml, respectively; p = 0.08), whereas no difference was observed in TGF-, among the same groups (134.7 ± 79.2, range 68,421 pg/ml, and 121.4 ± 25.8, range 75,151 pg/ml, respectively). Interestingly, a statistically significant inverse correlation was observed between IL-10 and TGF-, in kidney transplant recipients (p = 0.03). Conclusions:, The higher IL-10 production observed in long-term kidney transplant recipients supports the notion that this cytokine contributes in decreasing allogenic immune responses and allows prolongation of allograft survival. The balance between TGF-, and IL-10 may be of paramount importance in graft acceptance. [source] | ||||||||||