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1.
Circulating adhesion molecules during kidney allograft reperfusion   总被引:3,自引:0,他引:3  
Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant recipients, including 13 cases of delayed graft function (DGF) and 11 cases of acute graft rejection (AR). Plasma concentrations of E-selectin, VCAM-1 and ICAM-1 after 3 min of reperfusion were significantly higher than in the iliac vein before reperfusion. There was no statistically significant difference between patients with and without DGF as regards E-selectin, VCAM-1 and ICAM-1 concentrations in the iliac vein before and in the renal vein after 3 min of reperfusion. Concentrations of adhesion molecules in the iliac vein before reperfusion and in the renal vein after 3 min of reperfusion did not differ significantly between patients with and without AR except for ICAM-1 iliac vein concentration which was significantly increased in AR patients. Plasma levels of E-selectin, ICAM-1 and VCAM-1 were increased after kidney allograft reperfusion. Moreover, elevated serum levels of ICAM-1 before transplantation correlated with subsequent acute kidney allograft rejection. The results suggest that elevated ICAM-1 levels may be implicated in acute graft rejection.  相似文献   

2.
BACKGROUND: Renal allograft rejection is associated with the expression of adhesion molecules on vascular endothelial and tubular epithelial cells. METHODS: To assess whether the number of cell adhesion molecules expressed in donor kidneys can predict early rejection or delayed graft function, kidney biopsies from 20 living and 53 cadaveric kidney donors were obtained before engraftment into the recipients and the expression of the cell adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule (E-selectin) were determined by immunohistochemistry. RESULTS: All biopsies from living donors showed significantly lower expression of ICAM-1 and VCAM-1 compared to biopsies from cadaveric donors. There was no difference in the expression of adhesion molecules on tubular cells between transplants with primary function compared to allografts with early rejection in living donated kidneys (ICAM-1: 2+/-8 vs. 3+/-8%; VCAM-1: 9+/-7 vs. 1+/-1%), as well as in cadaveric kidneys (ICAM-1: 38+/-29 vs. 39+/-38%; VCAM-1: 55+/-27 vs. 48+/-29%). The expression of ICAM-1 molecules on tubular cells was determined to be a predictor for the occurrence of delayed graft function in cadaveric kidneys (ICAM-1: 65+/-24* vs. 38+/-29% delayed graft versus primary graft function). No delayed graft function occurred in recipients of living donated kidneys. CONCLUSIONS: These data suggest that adhesion molecule expression in donor biopsies is not a predictor for early allograft rejection, but can be used as a marker for the development of postischemic acute renal allograft failure.  相似文献   

3.
Delayed graft function (DGF) after kidney transplantation is associated with an increased risk of graft failure. We studied the histologic findings among adult kidney transplant recipients transplanted between January 2000 and June 2015 who had DGF and had a kidney biopsy within 14 days of transplant. Death censored graft failure (DCGF) and death at 1 and 3 years after transplant were examined. A total of 269 transplant recipients fulfilled our selection criteria, of which 152 (56.51%) had acute tubular necrosis (ATN), 44 (16.4%) had acute rejection (AR), mainly T-cell mediated rejection (n = 31), 35 (13%) had ATN with AR (mainly T-cell mediated rejection, n = 26), and 38 (14.1%) had other pathology. Compared with those with ATN alone, kidney transplant recipients with AR alone had a significantly higher risk of DCGF at 1 year post transplant (adjusted hazard ratio = 3.70; 95% confidence interval 1.5-9.5; P = .006). Those with AR alone had an increased risk of DCGF at 3 years post transplant (hazard ratio = 3.10; 95% confidence interval 1.3-8.5; P = .01) in crude analyses. There was no association between DGF etiology and mortality. Early renal biopsy can be used to distinguish AR, which has protocolized treatments, from other etiologies. This could potentially alter allograft survival within 1 year of transplant complicated by DGF.  相似文献   

4.
OBJECTIVE: To examine whether purine and pyrimidine nucleoside concentrations as well as oxypurine concentrations in renal and peripheral veins during reperfusion correlate with graft function parameters. MATERIAL AND METHODS: The study population comprised 25 recipients of cadaver kidney transplant. A first blood sample was taken from the recipient's peripheral vein before anastomosing the kidney allograft vessels with the recipient's iliac vessels. Subsequent samples were taken from the allograft renal vein and the recipient's peripheral vein 5 min after beginning reperfusion. High-performance liquid chromatography was done to measure plasma concentrations of the oxypurines hypoxanthine (Hyp), xanthine (Xan) and uric acid and the nucleosides guanosine, inosine (Ino) and uridine (Urd). RESULTS: Concentrations of Hyp, Xan and Ino were significantly higher in the renal than the peripheral vein. The differences between the Xan, Hyp, Ino and Urd plasma concentrations in the renal and peripheral veins before and 5 min after reperfusion correlated positively and significantly with serum creatinine concentrations 24 and 72 h after graft transplantation. Moreover, the concentrations of Hyp were significantly increased in renal transplant recipients with delayed graft function. CONCLUSION: The results of this study suggest that the concentration of Hyp in the kidney allograft vein can be a useful predictor of early graft function.  相似文献   

5.
目的探讨黏附分子ICAM-1、P-selectin、E-selectin、L-selectin、PECAM-1和VCAM-1在肝脏移植中的表达及意义。方法用免疫组织化学方法和原位杂交法,检测大鼠肝脏移植后不同时间(1、3、5、7d)、不同模型中ICAM-1、P-selectin、L-selectin、E-selectin蛋白、VCAM-1 mRNA、PECAM-1 mRNA的表达情况。结果肝急性排斥组与自发耐受组相比,黏附分子ICAM-1、VCAM-1、PECAM-1、E-selectin表达高;子代组与肝急性排斥组各指标表达类似,而ICAM-1的表达高于肝急性排斥组;半肝组与自发耐受组各指标表达类似,但ICAM-1、VCAM-1表达水平较自发耐受组高。P-selectin、L-selectin表达变化不明显。而正常大鼠肝脏未见黏附分子的表达。结论肝排斥反应可能与黏附分子ICAM-1、VCAM-1、PECAM-1、E-selectin的高表达有关。  相似文献   

6.
7.
The impairment of organ function due to ischemia-reperfusion injury is still an important problem in solid organ transplantation. Numerous experimental and clinical studies of native organs have shown that ischemia-reperfusion constitutes an acute inflammatory process involving cell surface adhesion molecule expression. These markers are crucial for the recruitment and infiltration of effector cells into the postischemic tissue. Purines released by the postischemic tissue as the products of the degradation of high-energy nucleotides can be regarded as markers of disturbed energy metabolism. The aim of this study was to examine the correlation between circulating adhesion molecules and purine metabolites in graft renal vein plasma during 49 cases of kidney reperfusion. E-selectin, ICAM-1, and VCAM-1 concentrations correlated positively with hypoxanthine concentrations during reperfusion, whereas the concentrations of ICAM-1 correlated negatively with xanthine concentrations. The results of the present study suggested that the concentrations of adhesion molecules in the renal vein during reperfusion correlated with purine metabolites, reflecting metabolic changes in renal tissue.  相似文献   

8.
BACKGROUND: The authors studied the impact of neutrophil activation, detected in experimental models, on reperfusion injury in clinical renal transplantation. METHODS: Forty-five patients from a larger trial comparing three immunosuppressive protocols were recruited: perioperative antithymocyte globulin (ATG) with low initial cyclosporine A (CsA) triple therapy (group A, n=15); two-dose basiliximab with low initial CsA triple therapy (group B, n=16); and conventional triple therapy (group C, n=14). Blood samples were obtained preoperatively, before reperfusion, and at 1 and 5 min after reperfusion. During reperfusion, samples were collected from the iliac artery and the graft vein for calculation of transrenal differences (Delta) of study parameters. Leukocyte differential counts, plasma lactoferrin concentration, and neutrophil CD11b and L-selectin expressions were assessed. Graft blood flow was measured at 2 and 30 min after reperfusion. RESULTS: ATG induced neutrophil activation already before reperfusion. Thus, group A was excluded, but groups B and C were pooled for analysis of reperfusion-induced neutrophil activation. At 1 min after reperfusion, lactoferrin concentration was higher in graft vein than iliac artery, yielding Delta=15 microg/L (P<0.05). Concomitantly, Delta neutrophil count correlated with both Delta L-selectin expression (R=0.49, P=0.012) and graft blood flow at 2 min (R=0.51, P=0.007). At 5 min after reperfusion, 0.17 (-1.0-0.24)x10 cells/L neutrophils were sequestered in the graft (P<0.001). This sequestration correlated with graft blood flow at 30 min (R=0.53, P=0.005) and was stronger in patients with delayed graft function (DGF) (Delta = -0.38 [-1.45 to -0.2]) than those without (Delta = -0.12 [-0.41-0.24], P<0.001). In multiple regression analysis, sequestration was the most important parameter associated with DGF. CONCLUSIONS: Neutrophils are activated and sequestered in the reperfused graft during clinical renal transplantation. Neutrophil sequestration is a powerful independent factor explaining the incidence of DGF.  相似文献   

9.
10.
The effect of recipient hepatitis C virus (HCV) infection on renal allograft loss and acute rejection in kidney transplantation remains controversial. We studied 354 renal allograft recipients transplanted during 1996 to 2001 who had HCV antibodies (Ab) measured before transplantation. The primary outcome was death-censored allograft loss and the secondary outcome was acute humoral rejection (AHR). Compared with HCV Ab-negative patients, those with positive HCV Ab had longer time on dialysis before transplantation, higher percentage of panel-reactive antibodies (PRA), were more likely to receive a cadaveric transplant, and were more likely to develop delayed graft function (DGF). In univariate analyses, predictors of renal allograft loss included HCV, cadaveric graft, PRA >20%, HLA mismatch > or =5, retransplantation, DGF, induction therapy, and AHR. When adjusted for PRA >20%, HLA mismatch > or =5, and multiple transplant status, HCV was not a statistically significant predictor of allograft loss. HCV was also associated with AHR but lost significance when adjusted for PRA >20%. HCV Ab-positive patients were more likely to have longer duration of dialysis before transplantation prior to kidney transplants, higher PRA, and to receive cadaveric transplants. These characteristics likely resulted in more DGF and AHR after transplantation. After adjusting for these confounding factors, the association between HCV Ab positivity and renal allograft loss was notably attenuated and no longer statistically significant.  相似文献   

11.
Poor early graft function (EGF) after deceased donor kidney transplantation (DDKT) has been intensely studied. Much less is known about poor EGF after living donor kidney transplantation (LDKT). Data were collected on 469 LDKTs performed between 1/1/97 and 12/31/01 to determine risk factors for and outcomes associated with poor EGF, defined as either delayed or slow graft function (DGF or SGF). The incidence of DGF and SGF were 4.7% and 10.7%, respectively. Diabetic etiology (OR 2.22; p = 0.021) and warm ischemia time (WIT) (OR 1.05 per min increment; p = 0.0025) emerged as independently associated with poor EGF. Neither functional graft survival nor 1-year graft function differed among the EGF groups. However, DGF and SGF strongly predisposed to acute rejection (AR), which compromised functional graft survival (p = 0.0007) and 1-year graft function. Therefore, we conclude that diabetic etiology of renal disease and WIT are the dominant risk factors for poor EGF after LDKT. Poor EGF did not directly compromise functional graft survival but strongly predisposed to AR. We suggest that immunosuppression should be intensified in the poor EGF setting to maximize LDKT longevity, as AR does impair functional graft survival.  相似文献   

12.
Qureshi F  Rabb H  Kasiske BL 《Transplantation》2002,74(10):1400-1404
BACKGROUND: The relationship between the effects of early, silent, acute rejection (AR) and delayed graft function (DGF) on kidney allograft survival remain controversial, and the role of protocol biopsies during DGF is unclear. We hypothesized that protocol biopsies during DGF would reveal a high incidence of silent AR that may adversely affect long-term allograft survival. METHODS: We routinely carried out protocol biopsies in patients requiring dialysis 7 to 10 days posttransplant. We retrospectively examined the extent to which silent AR, diagnosed by protocol biopsies during prolonged DGF, may mediate the adverse effects of DGF on graft survival in 410 consecutive transplants using Cox proportional hazards analysis. RESULTS: By 40 days posttransplant, the cumulative incidence of AR was 57.2% among 65 patients who had a protocol biopsies during DGF, while it was only 15.1% among the 345 who did not need a protocol biopsy. Mild DGF (n=30) requiring one or two dialysis treatments had no effect on graft survival, but the unadjusted risk ratio (and 95% confidence interval) associated with more prolonged DGF (n=104) was 3.08 (2.09-4.52, P<0.0001). The risk for graft failure from AR detected on protocol biopsy was 2.91 (1.60-5.27, P=0.0004) and was similar to the risk from early AR in patients without DGF, 2.95 (1.72-5.07, P<0.0001). After taking the effects of AR into account, the risk of graft failure attributable to prolonged DGF was reduced to 1.76 (1.06-2.94, P=0.0294), suggesting that much of the risk of DGF was because of the risk of AR. CONCLUSIONS: Silent AR is common during DGF. Prolonged DGF is associated with reduced graft survival after kidney transplantation, and much of this association can be explained by silent AR. In the absence of data from randomized trials, protocol biopsies and treatment of silent AR during prolonged DGF appear to be warranted.  相似文献   

13.
Delayed graft function (DGF) in kidney transplantation is associated with an increased risk of acute rejection. Myeloid dendritic cells (DCs) are involved in graft rejection, whereas plasmacytoid DCs may play a role in inducing tolerance. We evaluated the presence and phenotype of the DCs in renal graft biopsies of 15 patients with DGF collected before and 7-15 days after transplantation. Biopsies taken from normal patients and from transplant recipients with acute calcineurin inhibitors (CNIs) nephrotoxicity served as a control group. Specific markers of myeloid, plasmacytoid, and mature DCs were imaged by confocal microscopy and immunohistochemistry. In normal kidneys and pre-transplant biopsies, sparse niches of myeloid and plasmacytoid cells were found but these were significantly increased with few mature cells during DGF. This same pattern was seen in acute rejection but with overall higher cell numbers. In CNI nephrotoxicity, myeloid cells were slightly increased but plasmacytoid cells were significantly higher than in DGF. Using a pig model, we found that a short period of warm ischemia followed by reperfusion led to myeloid cell infiltration of the kidney. Our data suggest that ischemia-reperfusion injury may cause an imbalance between intragraft myeloid and plasmacytoid DCs, which might be related to DGF and acute rejection.  相似文献   

14.
目的 探讨凋亡及凋亡相关因子Fas/FasL、Bcl-2/Bax,粘附分子ICAM-1、P-selectin、E-selectin、L-Selectin、PECAM-1和VCAM-1在心脏移植中的表达及意义。方法 用免疫组织化学方法和原位杂交法,检测大鼠心脏移植后不同时间(1、3、5、7d)、Fas/FasL、ICAM-1、P-selectin、L-selectin、E-selectin蛋白、Bcl-2/Bax、VCAM-1、PECAM-1 mRNA的表达情况。结果 随着移植后天数的增加,细胞凋亡增多,Fas/FasL、Bax表达增加,粘附分子ICAM-1、VCAM-1、PECAM-1表达也增加,Selectin表达较少。正常大鼠肝脏未见细胞凋亡及粘附分子的表达。结论 细胞凋亡和粘附分子ICAM-1、VCAM-1、PECAM-1表达增加可能与心脏移植后急性排斥反应有关,而Fas/FasL、Bax可能促进了凋亡的发生。  相似文献   

15.
BACKGROUND: T-cell activation through T-cell receptor engagement requires co-stimulatory molecules and also adhesion molecules such as ICAM-1. Moreover ICAM-1 mediates leukocyte invasion from the blood into tissue during inflammatory processes. In animal studies using mouse monoclonal antibodies against ICAM-1 (enlimomab), renal allograft survival has been improved and reperfusion damage from ischemia reduced. The European Anti-ICAM-1 Renal Transplant Study (EARTS) was a randomized, double-blind, parallel-group, placebo-controlled study lastingl year and performed in 10 transplant centers in Europe. METHODS: A total of 262 recipients of cadaveric kidneys were given either enlimomab or a placebo for 6 days and were given triple immunosuppressive therapy of cyclosporine, azathioprine, and prednisolone. The primary efficacy endpoint was the incidence of the first acute rejection within 3 months, and each event was assessed by a committee including investigators and independent pathologists. RESULTS: There was no significant difference in the incidences of first acute rejection at 3 months between the placebo and enlimomab groups (39% vs. 45%), and enlimomab did not reduce the risk of delayed onset of graft function (DGF) (26% vs. 31%). Neither was there a difference in patient survival (95% vs. 91%) or graft survival (89% vs. 84%) at 1 year. Fatal events occurred in 19 (7%) patients (7 placebo, 12 enlimomab). Clinically, the most important non-fatal adverse events were infections; however, there was no statistically significant difference between the incidences in the two groups (70% vs. 79%). CONCLUSION: Short term enlimomab induction therapy after renal transplantation did not reduce the rate of acute rejection or DGF.  相似文献   

16.
We report a case of living related renal transplantation that used the recipient's saphenous vein as a graft to extend the length of the right donor renal vein.A 41-year-old woman underwent ABO-incompatible living related renal transplantation from her 74-year-old mother in November 2014.A retroperitoneal laparoscopic right donor nephrectomy was performed, because the right kidney showed a cyst on preoperative computed tomography.As the right kidney after donor nephrectomy had a short renal vein and the kidney was large at 280 g, anastomosis with the external iliac vein was difficult. Therefore, we obtained the recipient's 15-cm-long right saphenous vein and created a 1 cm saphenous vein graft. We anastomosed 1 side of the saphenous vein graft to the allograft renal vein in bench surgery and performed end-to-side anastomosis of the other end to the recipient's external iliac vein. The allograft renal artery was used to perform end-to-end anastomosis to the recipient's internal iliac artery. Allograft kidney function was good after transplantation.When the longer axis of the renal graft vein is short, as in the right kidney, a saphenous vein graft may be useful.  相似文献   

17.
Delayed graft function (DGF) is a common complication of deceased donor kidney transplantation with negative impact on clinical outcomes. In a single‐center retrospective analysis, we compared patient and kidney survival, early renal function, and the incidence of acute rejection during the first year among all adult deceased donor kidney transplant patients without DGF, with DGF requiring one‐time and/or more than one‐time dialysis treatment between January 1, 2000, and December 31, 2008. Of 831 adult kidney transplant patients, 74 (8.9%) required one‐time and 134 (16.1%) more than one‐time dialysis treatment post‐transplantation, respectively. While DGF patients with one‐time dialysis treatment had comparable clinical outcomes to that of patients without DGF, patients with DGF requiring more than one‐time dialysis treatment had a 45% increased risk for death (HR 1.45, 95% CI 1.02, 2.05, p = 0.04) after adjustment for the differences in demographic and baseline characteristics. Furthermore, DGF patients with more than one‐time dialysis requirement displayed significantly lower renal function after recovery (OR 0.32, 95% CI 0.21, 0.49, p < 0.001, for eGFR ≥ 60 mL/min) and higher incidence of acute rejection during the first year (OR 1.66, 95% CI 1.11, 2.49, p = 0.015). Additional studies of therapeutic approaches to manage patients with prolonged DGF are needed.  相似文献   

18.
BACKGROUND: There is mounting evidence from experimental and clinical studies that the quality of organs from cadaver donors may be influenced by events occurring around the time of brain death, and that these may affect transplant outcome. The aim of this study is to investigate the influence of donor factors on renal allograft outcome in a homogeneous cohort of 518 patients transplanted in a single centre over a 9 year period. METHODS: Endpoints of the study were delayed graft function (DGF), acute rejection (AR), 1 year graft survival and long-term survival of those grafts that reached 1 year. Multivariate analysis was performed to determine factors that may have influenced the graft outcome indicators. RESULTS: DGF was the major predictor of graft failure overall with cold ischaemia time (CIT) as an important independent factor. The level of histocompatibility did not influence graft survival. DGF was the major factor affecting 1 year graft survival (P<0.0005) with effects persisting beyond 1 year. DGF was significantly influenced by CIT, donor age, female kidney into male recipient and donor creatinine (P<0.05). Other donor factors and factors associated with donor management were not risk factors for DGF, rejection episodes or graft survival. The risk factors for a number of AR episodes were HLA-DR mismatch and DGF (P<0.005). When grafts surviving for 1 year were considered, only CIT, recipient age and creatinine at 1 year (P<0.05) were found to affect graft survival significantly. CONCLUSIONS: The results of this analysis of well-matched transplant recipients show that CIT and DGF are the most important predictors of poor short and long-term graft survival. Therefore, in order to improve the long-term survival of renal allografts efforts should focus on limiting CIT and the damage that occurs during this period and on improving our understanding of DGF.  相似文献   

19.
Perforin (P), Granzyme B (GB) and Fas-Ligand (FAS-L) are cytotoxic molecules involved in acute rejection (AR) after renal transplantation. A noninvasive diagnostic test to monitor AR and other complications could improve clinical management. We investigated the predictive and diagnostic interest of target mRNA measurements, with a quantitative PCR assay, in AR, as well as in other clinical complications recurrent in kidney transplantation. One hundred and sixty-two urine specimens from 37 allograft recipients were investigated. Clinical settings were AR, urinary tract infection (UTI), cytomegalovirus infection (CMVi) or disease (CMVd), chronic allograft nephropathy (CAN), delayed graft function (DGF) and stable graft course (controls). In the case of AR, mRNA levels of all three molecules were significantly higher than in recipients not showing any clinically evident signs of complication. Indeed, it was observed that expression levels of P, GB and Fas-L mRNA also increase in other clinical situations such as UTI, CMV and DGF. Finally, kinetic studies in three patients with AR revealed that increased P, GB and Fas-L mRNA levels could precede or were concomitant with increased serum creatinin levels. P, GB and Fas-L gene expression in urine specimens were upregulated in AR episodes but also in UTI, CMV infection and DGF. Therefore, this technique would appear to be of limited clinical value as a noninvasive method of diagnosing AR.  相似文献   

20.

Objective

Renal transplantation is the best options for treating end-stage renal disease. Better patient and allograft survival rates are provided by living donation, which has been safe, with minimal immediate and long-term risk for the donor. This study aims to investigate the life status and summarize the clinical experience in living-related kidney transplant (LRKT) before and after renal transplantation.

Methods

A total of 310 cases of LRKT have been performed in our center since 1998. Tissue matching and risk factors assessment in donors and recipients were performed before donation. Small lumbar incision was used in all cases for unilateral nephrectomy. Donors and recipients were followed up regularly after renal transplantation.

Results

All living donors were healthy, with normal renal function after unilateral nephrectomy. The 1- and 5-year patient/graft survival rates of LRKT were 98.3 %/97.6 % and 91.3 %/86.9 %, respectively. The cumulative incidence of delayed graft function (DGF) and acute rejection (AR) was 2.9 % (9 cases). Thirteen cases developed pulmonary infection (4.2 %) and eight cases were cured. The graft function in most cases returned to normal range soon after kidney transplant. Moreover, the creatinine and BUN levels of grafts donated by children or siblings of recipients were markedly lower than those donated by parents, at 1 month after transplant.

Conclusion

Adequate pretransplant assessment, better tissue matching, and reduced ischemia time may result in lower incidence of DGF, AR and higher patient/graft survival rates for LRKT. It is important to improve selection criteria and health assessment of donors. Long-term follow-up is essential to ensure a healthy life for donors and recipients after kidney transplant.  相似文献   

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