Younger Donors (younger + donor)

Distribution by Scientific Domains

Selected Abstracts

Cellular senescence in pretransplant renal biopsies predicts postoperative organ function

AGING CELL, Issue 1 2009
Liane M. McGlynn
Summary Older and marginal donors have been used to meet the shortfall in available organs for renal transplantation. Post-transplant renal function and outcome from these donors are often poorer than chronologically younger donors. Some organs, however, function adequately for many years. We have hypothesized that such organs are biologically younger than poorer performing counterparts. We have tested this hypothesis in a cohort of pre-implantation human renal allograft biopsies (n = 75) that have been assayed by real-time polymerase chain reaction for the expression of known markers of cellular damage and biological aging, including CDKN2A, CDKN1A, SIRT2 and POT1. These have been investigated for any associations with traditional factors affecting transplant outcome (donor age, cold ischaemic time) and organ function post-transplant (serum creatinine levels). Linear regression analyses indicated a strong association for serum creatinine with pre-transplant CDKN2A levels (p = 0.001) and donor age (p = 0.004) at 6 months post-transplant. Both these markers correlated significantly with urinary protein to creatinine ratios (p = 0.002 and p = 0.005 respectively), an informative marker for subsequent graft dysfunction. POT1 expression also showed a significant association with this parameter (p = 0.05). Multiple linear regression analyses for CDKN2A and donor age accounted for 24.6% (p = 0.001) of observed variability in serum creatinine levels at 6 months and 23.7% (p = 0.001) at 1 year post-transplant. Thus, these data indicate that allograft biological age is an important novel prognostic determinant for renal transplant outcome. [source]

Aging stimulates cyclooxygenase-2 expression and prostaglandin E2 production in human periodontal ligament cells after the application of compressive force

Kotoe Mayahara
Background and Objectives:, Some clinical studies show that alveolar crestal bone loss is higher in adults than in young patients during orthodontic treatment, but the causes of such a phenomenon have not been elucidated. It is known that prostaglandin E2 (PGE2) is a proinflammatory agent and one of the potent osteoclast-inducing factors, and is produced by human periodontal ligament cells in response to orthodontic force. The aim of this study was to investigate age-related change in the biosynthetic capacity of PGE2 and its regulatory gene, cyclooxygenase 2 (COX-2) from periodontal ligament cells in response to mechanical stress. Methods:, Compressive force of 2 g/cm2 was applied for 3,48 h to periodontal ligament cells obtained from human donors aged 9,50 years, and COX-2 mRNA expression in and PGE2 production by the periodontal ligament cells in response to the compressive force were examined. Results:, Application of a compressive force of 2 g/cm2 for 3,48 h significantly stimulated these factors in both time- and age-dependent manners. Furthermore, these increases were dramatically larger in periodontal ligament cells obtained from donors over the age of 35. Conclusions:, Periodontal ligament cells obtained from old donors have significantly greater COX-2 expression and PGE2 production in response to compressive force than those from younger donors. The turning point of aging, where significantly larger amounts of theses factors begin production, appears to be around the age of 35. These results may be positively related to the acceleration of alveolar crestal bone loss during orthodontic treatment in adult patients. [source]

Liver grafts from donors with central nervous system tumors: A single-center perspective

Randeep Kashyap
Traditionally, patients who die with a malignancy have been excluded from donation. However, it has become a common practice to accept organs from donors that have low-grade tumors or tumors with low metastatic potential. The aim of this study was to analyze our experience with the use of liver grafts from donors with central nervous system (CNS) tumors. A retrospective review of 1173 liver transplants performed between 1992 and 2006 identified 42 donors diagnosed with a CNS tumor. Thirty-two tumors were malignant, and 10 tumors were benign. Forty-two liver transplant recipients received livers from these donors. All patients were followed until May 2007 with a mean follow-up of 29 17 months. Among 42 donors, there were 28 males and 14 females. The mean donor risk index was 1.78 0.39. Twenty (47.6%) of the CNS tumors were glioblastoma multiforme (astrocytoma grade IV), 11 (26.2%) were other astrocytomas, and 1 (2.4%) was an anaplastic ependymoma. Twenty (62.5%) neoplasms were grade IV tumors, 8 (25%) were grade II tumors, and 4 (12.5%) were grade III tumors. Over 80% of the patients had at least 1 kind of invasive procedure violating the blood-brain barrier. The rate of recurrence for the entire group was 2.4% (all CNS tumors). There were 7 (7.2%) deaths in all. The most common cause of death was sepsis (n = 3, 7.2%). There was no difference in survival between recipients of grafts from donors with CNS tumors and recipients of grafts from donors without CNS tumors (1 year: 82% versus 83.3%, P = not significant; 3 years: 77.4% versus 72%, P = not significant). In conclusion, in our experience, despite violation of the blood-brain barrier and high-grade CNS tumors, recurrence was uncommon. Grafts from these donors are often an overlooked source of high-quality organs from younger donors and can be appropriately used, particularly in patients who, despite low Model for End-Stage Liver Disease scores, carry a high risk of mortality. Liver Transpl 15:1204,1208, 2009. 2009 AASLD. [source]

Mycophenolate mofetil without antibody induction in cadaver vs. living donor pediatric renal transplantation

O. Ojogho
Abstract: Mycophenolate mofetil (MMF) is a new immunosuppressive agent that blocks de novo purine synthesis in T and B lymphocytes via a potent selective inhibition of inosine monophosphate dehydrogenase. MMF has been shown to significantly reduce the incidence of acute rejection in both adult and pediatric renal transplantation. The impact of MMF on routine antibody induction therapy in pediatric renal transplantation has not been defined. Remarkably, a recent North American Pediatric Transplant Cooperative Study concluded that T-cell antibody induction therapy was deleterious for patients who received MMF. Our study examines the use of MMF in an evolving immunosuppressive strategy to avoid antibody induction in both living (LD) and cadaver (CAD) donor pediatric renal transplantation. We retrospectively analyzed the records of 43 pediatric renal transplants that received MMF-based triple therapy without antibody induction therapy between November 1996 and April 2000. We compared CAD (n = 17) with LD (n = 26). The two groups were similar demographically except that CAD had significantly younger donors than LD, 26.1 13.7 vs. 36.2 9.2 yr (p = 0.006). All the patients received MMF at 600 mg/m2/b.i.d. (maximum dose of 2 g/d) and prednisone with cyclosporine (86%) or tacrolimus (14%). Mean follow-up was >36 months for each group. Acute rejection rate at 6 months was 11.8% (CAD) vs. 15.4% (LD) (p = 0.999) and at 1 yr was 23.5% (CAD) vs. 26.9% (LD) (p = 0.999). Mean estimated glomerular filtration rate (ml/min/1.73 m2) at 6 months was 73.3 15.3 (CAD) vs. 87.6 24.2 (LD) (p = 0.068). Patient survival at 1, 2, and 3 yr was 100, 100, and 100% for CAD vs. 100, 96, and 96% for LD, respectively. Graft survival at 1, 2, and 3 yr was 100, 100, and 94% for CAD vs. 96, 88, and 71% for LD, respectively. Graft loss in CAD was because of chronic rejection (n = 2) while in LD it was because of non-compliance (n = 6), post-transplant lymphoproliferative disorder (n = 1), and sepsis (n = 1). In conclusion, MMF without antibody induction in both CAD and LD pediatric renal transplantation provides statistically similar and effective prophylaxis against acute rejection at 6 months and 1 yr post-transplant. The short-term patient and graft survival rates are excellent, however, non-compliance remains a serious challenge to long-term graft survival. Additional controlled studies are needed to define the role of MMF without antibody induction therapy in pediatric renal transplantation. [source]

Multicenter Analysis of Novel and Established Variables Associated with Successful Human Islet Isolation Outcomes

J. S. Kaddis
Islet transplantation is a promising therapy used to achieve glycometabolic control in a select subgroup of individuals with type I diabetes. However, features that characterize human islet isolation success prior to transplantation are not standardized and lack validation. We conducted a retrospective analysis of 806 isolation records from 14 pancreas-processing laboratories, considering variables from relevant studies in the last 15 years. The outcome was defined as postpurification islet equivalent count, dichotomized into yields ,315 000 or ,220 000. Univariate analysis showed that donor cause of death and use of hormonal medications negatively influenced outcome. Conversely, pancreata from heavier donors and those containing elevated levels of surface fat positively influence outcome, as did heavier pancreata and donors with normal amylase levels. Multivariable logistic regression analysis identified the positive impact on outcome of surgically intact pancreata and donors with normal liver function, and confirmed that younger donors, increased body mass index, shorter cold ischemia times, no administration of fluid/electrolyte medications, absence of organ edema, use of University of Wisconsin preservation solution and a fatty pancreas improves outcome. In conclusion, this multicenter analysis highlights the importance of carefully reviewing all donor, pancreas and processing parameters prior to isolation and transplantation. [source]

Recipient Outcomes for Expanded Criteria Living Kidney Donors: The Disconnect Between Current Evidence and Practice

Y. Iordanous
Older individuals or those with medical complexities are undergoing living donor nephrectomy more than ever before. Transplant outcomes for recipients of kidneys from these living expanded criteria donors are largely uncertain. We systematically reviewed studies from 1980 to June 2008 that described transplant outcomes for recipients of kidneys from expanded criteria living donors. Results were organized by the following criteria: older age, obesity, hypertension, reduced glomerular filtration rate (GFR), proteinuria and hematuria. Pairs of reviewers independently evaluated each citation and abstracted data on study and donor characteristics, recipient survival, graft survival, serum creatinine and GFR. Transplant outcomes for recipients of kidneys from older donors (,60 years) were described in 31 studies. Recipients of kidneys from older donors had poorer 5-year patient and graft survival than recipients of kidneys from younger donors [meta-analysis of 12 studies, 72% vs. 80%, unadjusted relative risk (RR) of survival 0.89, 95% confidence interval (CI) 0.83,0.95]. In meta-regression, this association diminished over time (1980s RR 0.79, 95% CI 0.65,0.96 vs. 1990s RR 0.91, 95% CI 0.85,0.99). Few transplant outcomes were described for other expanded criteria. This disconnect between donor selection and a lack of knowledge of recipient outcomes should give transplant decision-makers pause and sets an agenda for future research. [source]

FOXP3 Expression in Human Kidney Transplant Biopsies Is Associated with Rejection and Time Post Transplant but Not with Favorable Outcomes

S. Bunnag
Expression of the transcription factor forkhead box P3 (FOXP3) in transplant biopsies is of interest due to its role in a population of regulatory T cells. We analyzed FOXP3 mRNA expression using RT-PCR in 83 renal transplant biopsies for cause in relationship to histopathology, clinical findings and expression of pathogenesis-based transcript sets assessed by microarrays. FOXP3 mRNA was higher in rejection (T-cell and antibody-mediated) than nonrejection. Surprisingly, some native kidney controls also expressed FOXP3 mRNA. Immunostaining for FOXP3 was consistent with RT-PCR, showing interstitial FOXP3+ lymphocytes, even in some native kidney controls. FOXP3 expression correlated with interstitial inflammation, tubulitis, interstitial fibrosis, tubular atrophy, C4d positivity, longer time posttransplant, younger donors, class II panel reactive antibody >20% and transcript sets reflecting inflammation and injury, but unlike these features was time dependent. In multivariate analysis, higher FOXP3 mRNA was independently associated with rejection, T-cell-associated transcripts, younger donor age and longer time posttransplant. FOXP3 expression did not correlate with favorable graft outcomes, even when the analysis was restricted to biopsies with rejection. Thus FOXP3 mRNA expression is a time-dependent feature of inflammatory infiltrates in renal tissue. We hypothesize that time-dependent entry of FOXP3-positive cells represents a mechanism for stabilizing inflammatory sites. [source]