Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Remarkable increases in cadaveric renal transplant survival rates have been seen following improvements in areas such as immunosuppression, organ preservation, HLA typing and cross-matching, and blood transfusion protocols. However, while these improvements have influenced survival in the early post-transplant period up to 6 months, the cumulative rate of graft loss beyond the 1st year has remained constant at about 9% a year over the past 25 years. Several factors that affect long-term survival have been identified through univariate and multivariate analyses. Chief among these is the detrimental effect of HLA-A and HLA-B antigen mismatching. Also important are the recipient's race, sex, and age, and presence of diabetes, as well as the donor's age, sex, and cause of death, and long cold ischemia times. Likewise, post-transplant events, including delayed graft function, early rejection episodes, and discharge serum creatinine levels strongly affect long-term graft survival. Chronic rejection should also be recognized as a major contributor to the long-term failure rate, but there is currently no reliable way to identify or classify it in the UNOS Scientific Renal Transplant Registry database. Characteristics that define chronic rejection must be identified to allow transplant centers to accurately report its incidence and to enable investigators to analyze and monitor its impact on transplant outcome.
 ...
PMID:Outcome statistics of renal transplants with an emphasis on long-term survival. 806 74

Equitable allocation of human cadaver kidneys is complex and challenging, both from the ethical and scientific points of view. It is based on the principles of distributive justice and medical utility. However, the optimal application of ethical principles will require further resolution of medical issues that currently focus on the number of transplants for a single patient, six antigen matches, lesser degrees of HLA matching, marginal recipients, various positive cross-match situations, and cold ischemia time. New HLA matching techniques and enhanced computer organ allocation systems have the potential to surmount racial differences and increase significantly the number of compatible renal allografts.
 ...
PMID:Allocation of cadaver kidneys: new pressures, new solutions. 807 82

We reviewed a series of 500 transplants and found 21 (4.1%) cases of graft rupture. All the renal grafts had been harvested from cadavers. Hemodialysis was required in 18 (85%), acute rejection developed in 12 and acute tubular necrosis in 12 (3 were related to percutaneous maneuvers for biopsy or PCN). All cases developed acute pain and oligoanuria. No significant difference was observed relative to ischemia time or HLA typing. Concerning immunosuppression and graft rupture, a significant difference was observed for the group that received low dose CsA combined with triple therapy (3 rupture grafts, 14.2%) versus the high dose CsA and steroid treated group (11 ruptured grafts, 52.3%), p < 0.01. Twenty grafts had ruptured within the first 15 days following transplantation and one at 8 months. Graft removal was warranted in 8 (38%) and conservative surgery in 12 (57%). Two grafts (16%) were lost and 1 patient (4.7%) died without undergoing surgery. Graft rupture is a severe complication that warrants immediate surgical management. Conservative surgery is a valid alternative in those cases with a viable graft.
 ...
PMID:[Spontaneous rupture of transplanted kidney. Experience with 500 transplants]. 833 69

We propose that tissue-specific alloantigens are of importance in interstitial and vascular rejection. To study this hypothesis we took the following approaches: multivariate analysis on our database (N = 482) was performed, the specificity of T cells cultured from kidneys with rejection was analyzed, and non-anti-HLA antibodies reactive with endothelium were studied. First we observed that in a cohort study of 482 patients receiving a cadaveric renal allograft 76 (15.8%) patients developed vascular rejection and 115 (23.9%) developed interstitial rejection. The incidence of vascular rejection was increased in patients with delayed graft function, HLA-DR mismatches, a prolonged cold ischemia period, and previous transplantations. Next we examined 40 graft infiltrating cell (GIC) lines cultured from renal biopsies taken during rejection episodes. Thirteen GIC lines reacted in a donor-specific fashion to proximal tubular cells (PTEC) but not to donor splenocytes. These GIC recognize polymorphic tissue-specific peptides in the context of allo-MHC Class I. Finally, we studied if non-conventional allo-antigen systems on endothelial cells could be the target of the humoral immune response during vascular rejection. We found the endothelial monocyte (EM) system, and another system that is present on endothelial cells and platelets, which can be tested in an antibody-dependent cellular cytotoxicity assay (ADCC).
 ...
PMID:Tissue antigens in tubulointerstitial and vascular rejection. 858 71

Univariate and multivariate analyses have been performed on donor an d recipient variables to determine possible effects on the outcome of 516 primary cadaveric renal transplants performed in our single center from 1989 until 1993. The overall actuarial patient survival at 1 year and 5 years was 94.4% and 87.4%, respectively; the 1 year and 5 year graft survival rates were 88.3% and 77.8%, respectively. A total of 95 grafts were lost; death with function (35%) and chronic rejection (22%) were the major causes. Three variables (HLA-DR mismatch, delayed graft function, and prolonged cold ischemia time) had a significant detrimental effect on both short- and long-term graft survival. Zero HLA-DR mismatched grafts showed significantly enhanced survival over those with 1 HLA-DR mismatch both at 1 year (92.8% vs. 84.5%) and at 5 years (88.3% vs. 73.9%) only if cold ischemia time was less than 26 hours (P=0.0009). Occurrence of delayed graft function significantly lowered graft survival at both 1 year and 5 years (P=0.002), and the incidence was significantly associated with prolonged cold ischemia time (P<0.0001). HLA-A or HLA-B matching, percentage panel reactive antibodies (PRA), and anastomosis time showed no independent effect on long-term survival. The small number of 2 HLA-DR mismatched grafts (n=6) precluded separate analysis of this group. Acute rejection accounted for 12% of losses but had no statistically significant effect on graft survival, even though an increased frequency of rejection episodes was significantly associated with HLA-DR mismatch (P<0.0001). These results would suggest that significant survival benefits may be achieved by prospective HLA matching if cold ischemia times are limited. The efficiency of organ sharing must he improved to make optimal use of a limited resource.
 ...
PMID:Importance of minimizing HLA-DR mismatch and cold preservation time in cadaveric renal transplantation. 860 72

We previously reported that delayed graft function (DGF) in the absence of biopsy-proven acute rejection (Rej) had no effect on outcome of primary cadaver kidney transplantation (TX). By contrast, DGF in combination with Rej strongly predicted poor long-term graft survival. We asked whether this poor long-term outcome was due to early graft loss associated with DGF, or to an ongoing process leading to late graft loss. To answer this question, we studied a subset of 298 cadaver kidney transplant recipients who had not suffered early graft loss and had a serum creatinine level < or = 2.0 mg/dl at 1 year after TX. The incidence of DGF (defined by dialysis during the first week after TX) in this subset was 19%. DGF was associated with cold ischemia time >24 hr (P = 0.0003) and Rej (P = 0.06). For grafts with versus without DGF, the incidence of late acute Rej (>1 year after TX) was similar. Actuarial graft survival was similar for Rej-free recipients with versus without DGF (P = 0.9) and was worse for those with Rej and no DGF (P < 0.02). Importantly, however, in our recipients who all had a serum creatinine level < or = 2.0 mg/dl at 1 year after TX, the worst long-term outcome was noted in the subgroup with both DGF and Rej (P < 0.0001). By multivariate analysis, DGF was also only a risk factor in combination with Rej (P = 0.002, relative risk = 3.7), while a 0-antigen HLA mismatch had no impact. Patient survival decreased for recipients with both DGF and Rej by univariate (P = 0.009) and multivariate (P = 0.02, relative risk = 2.9) analyses. We conclude that DGF without Rej has no impact on long-term survival. However, our data for recipients with both DGF and Rej suggest that a chronic ongoing process leads to late graft failure. Further research is necessary to identify the exact pathophysiology of this process, which appears to be, at least in part, HLA antigen independent.
 ...
PMID:Delayed graft function in the absence of rejection has no long-term impact. A study of cadaver kidney recipients with good graft function at 1 year after transplantation. 862 92

Donor-recipient histocompatibility, as evaluated by the HLA matching results, plays an important role in the outcome of renal transplants, although much controversy surrounds the benefit of kidney allocation based on HLA typing. In this report HLA matching and survival data on 1,342 transplants performed at the University of California at San Francisco between 1984 and 1992 and treated uniformly by quadruple immunosuppression were analyzed in relation to the recipient's age. With respect to the influence of the increasing number of mismatches from 0 to 6, the analysis revealed decreasing 3-year graft survival rates as follows: 85.4%; 87.3%; 71.3%; 78.2%; 75.8%; 70.9% and 67.5%. Whereas the impact of cold ischemia time and histocompatibility was equally important during the 3-year postoperative period, the essential positive influence of good HLA matching on the long-term graft survival was demonstrated. The children aged between 5 and 18 years were identified as a high-risk group by the analysis, HLA-A incompatibility being attributed to poor graft survival in this age group. With respect to the effect of HLA-A histoincompatibility, the data provide evidence that HLA-A matching results seem to play an important role in graft survival in children, whereas transplants well matched in terms of HLA-B did well in adult recipients. No age difference in the impact of HLA-DR could be detected. In conclusion, HLA matching is still essential. It seems that there are differences in the impact of HLA loci in relation to the recipient's age.
 ...
PMID:[Effect of HLA compatibility on the transplanted kidney in relation to recipient age]. 865 Aug 46

Although successful simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia in the majority of diabetic recipients with end-stage renal disease, little is known about the factors that influence long-term endocrine function. In this prospective study of 48 bladder-drained SPK patients, 209 oral glucose tolerance tests were performed between 3 months and 6 years after transplantation. Normal fasting glucose levels and systemic hyperinsulinemia were stable for up to 6 years after SPK. Multivariate analysis revealed that increased area-under-curve (AUC) levels of C-peptide 3 months after transplantation were predicted by short surgical pancreas anastomosis time, greater recipient body weight, and total HLA mismatch score. Episodes of acute pancreas rejection were not associated with reduced allograft insulin output in the long term. Insulin output, stimulated by oral glucose tolerance tests and assessed by the ratio of AUC insulin to AUC glucose, fell gradually after transplantation and was decreased by an elevated serum calcium level and high cyclosporine dose. The ratio of fasting insulin to glucose, which acts as a marker of peripheral insulin resistance, fell with time after transplantation and was increased by greater body weight, higher prednisolone dose, and lower cyclosporine dose. The inhibitory effect of cyclosporine on both fasting and postprandial insulin output was, however, minor when quantified by multivariate analysis. Endocrine function of the transplanted pancreas was not correlated with its exocrine function measured by urinary amylase excretion, nor was there a correlation with change in renal function measured by isotopic glomerular filtration rate. In summary, simultaneous pancreas and kidney transplantation leads to excellent long-term glucose homeostasis maintained at the expense of systemic hyperinsulinemia. The key factors adversely affecting peripheral resistance in SPK were corticosteroid therapy, body weight, and time after transplantation. The susceptibility of islets to ischemia-reperfusion injury, as quantitated by surgical anastomosis time, may have implications for islet transplantation programs, as may the relative resistance of islets to allograft rejection. Glucose homeostasis after SPK, while remaining abnormal, may be used as the standard against which islet transplantation must be measured.
 ...
PMID:Clinical determinants of glucose homeostasis after pancreas transplantation. 868 47

Transplantation-related pathogenic factors such as ischemia or allograft-directed inflammation are associated with oxidative changes that might lead to cellular oxidative stress. The aim of this study was to investigate the impact of oxidative stress on: (1) CMV replication in cultured human endothelial cells and (2) the stimulation of endothelial cells by proinfiammatory cytokines. Both pathomechanisms are known to contribute to graft rejection crises in vivo. Oxidative stress was induced in endothelial cell cultures with 10-200 microM buthionine sulfoximine. Western blotting showed a significant increase in the production of CMV-specific immediate early and late proteins in buthionine sulfoximine-treated cultures. Immunocytochemical staining suggested that this effect was caused by increased numbers of CMV antigen expressing cells (66% immediate early; 78%, late). Quantitative polymerase chain reaction for CMV-specific DNA and virus titration revealed that enhanced viral replication levels correlated with increased virion production. As a measure for the endothelial cell activation status, the surface expression of HLA-ABC and HLA-DR and adhesion molecules (ICAM-1, ELAM-1, VCAM-1) was quantified by fluorometric methods. Whereas oxidative stress alone did not modulate any surface molecule expression, the IFN-gamma-mediated expression of HLA-ABC and HLA-DR and the IL-1-mediated expression of ICAM-1, but not of ELAM-1 and VCAM-1 (IL-1 + TNF-alpha), was amplified. Interestingly, the amplification of HLA molecule expression was even higher in CMV-infected endothelial cells. This study provides evidence that oxidative stress contributes to the regulation of CMV replication, virus shedding, and the activation of endothelial cells by proinflammatory cytokines as it is observed in transplant recipients.
 ...
PMID:Impact of oxidative stress on human cytomegalovirus replication and on cytokine-mediated stimulation of endothelial cells. 868 57

Post-transplant cure tubular necrosis (ATN) represents the most frequent cause of delayed graft function in the immediate post-transplant period. Several causes have been associated with the development of post-transplant ATN such as donor and recipient ages, cold-warm ischemia times, HLA mismatches, and postoperative hypotension. In the present study, we retrospectively evaluated the role of secondary hyperparathyroidism and high parathyroid hormone (PTHi) blood levels in the development of post-transplant ATN. One hundred patients submitted to cadaveric renal transplant between January 1992 and March 1993 in our unit were included. Twenty-seven patients (27%) developed post-transplant ATN and seventy-three (73%) did not. Post-transplant ATN was significantly associated with gender (p < 0.01), recipient age (p < 0.01), number of transplantations (p < 0.01), time on hemodialysis (p < 0.001), cold ischemic time (p < 0.05) and PTHi levels (p < 0.001). The bivariate and multivariate statistical analyses demonstrated that the development of post-transplant ATN was significantly more frequent in females; retransplanted patients, patients with a time on dialysis of more than 5 years, recipients over 60 years old, patients with a PTHi blood level higher than 240 pg/ml (4 times normal level) and a cold ischemia time of more than 18 h. Based on these results, we conclude that high PTHi blood levels in the renal transplant recipients represent a relevant factor in the development of post-transplant ATN. The administration of intravenous pulsed of 1,25(OH)2D3 and/or a calcium channel blocker in the perioperative period could be useful to decrease the incidence and severity of post-transplant ATN in these patients.
 ...
PMID:Role of secondary hyperparathyroidism in the development of post-transplant acute tubular necrosis. 874 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>