肾移植预后影响因素的COX模型分析

目的探讨影响肾移植预后的主要因素.方法采用寿命表法和COX回归模型对249例肾移植患者以性别、年龄、治疗方案选择、并发症等因素作为分析因子,计算生存率,分析预后影响因素.结果249例肾移植患者术后存活满1、2、3年的生存概率分别为72.6%、56.0%、40.8%,4年和5年生存概率均为22.5%,中位生存时间34.9个月.随着治疗时间延长,霉酚酸酯方案治疗者生存状况优于硫唑嘌呤方案者,中位生存期分别为38.9个月和30.6个月;COX回归模型提示影响肾移植预后主要因素依次为治疗方案、移植后随访时间、药物依从性、急性排斥反应、性别及住院时间（P＜0.05）.结论应用寿命表和COX回归模型分析评价肾移植患者预后生存状况以及影响因素是一种较为理想的方法.     

Iranian model of renal allograft transplantation in 3028 recipients: survival and risk factors

BACKGROUND: Considering the organ shortage crisis for renal transplantation worldwide, assessing the risk factors to establish better allocation strategies to improve graft survival seems to be crucial. OBJECTIVES: We aimed to evaluate the risk factors influencing graft and patient survival after renal transplantation to construct a model of prognostic factors for living renal transplantation (LRT), namely living unrelated renal transplantation (LURT). METHODS: We designed a retrospective multicenter survey including medical record review of 3028 patients who received renal transplants at 2 hospitals between July 1984 and December 2005. We assessed the impact on graft survival of recipient/donor relationship, recipient age and gender, donor age and gender, and viral hepatitis B and C infections. RESULTS: Among 3028 recipients, including 94.8% primary grafts, 63.4% were men, mean +/- SE of age 36.4 +/- 0.3 years, with mostly end-stage renal disease due to diabetes mellitus, hypertension, or glomerulonephritis. One-, 5-, 10- and 15-year graft survival rates were 85.4%, 68.3%, 46.4%, and 23.8%, respectively. Patient survival rates were 93.4%, 87.5%, 79.4%, and 66.4% at the above intervals, respectively. Donor age (relative hazard [RH], 1.024; P<.001), unrelated donors (RH, 1.7; P<.001), and hepatitis C virus (HCV) infection (RH, 2.65; P<.001) were the only significant factors affecting graft survival. CONCLUSION: Increased donor age, unrelated donor, and HCV infection were significant factors negatively impacting graft survival; thus, proper management of these factors may lead to better graft and patient survival.     

Impact of cadaveric renal transplantation on survival in patients listed for transplantation

The aim of this study was to assess the magnitude of the survival benefit of renal transplantation compared with dialysis in patients selected for transplantation in Scotland. Longitudinal study of survival and mortality risk in all adult patients (1732) listed for a first transplant between January 1, 1989, and December 31, 1989, in Scotland. A time-dependent Cox regression analysis adjusted for comorbidity, sociodemographic and geographic factors, primary renal disease, time on dialysis, and year of listing compared the risk of death for patients receiving a first cadaveric transplant versus all patients on dialysis listed for transplantation. After adjustment for the covariates, the relative risk (RR) of death during the first 30 days after transplantation was 1.35 (95% confidence interval [CI], 0.63 to 2.86) compared with patients on dialysis (RR = 1). The long-term RR (at 18 mo) for the transplant recipients was 0.18 (95% CI, 0.08 to 0.42) when compared with patients on dialysis (RR = 1). This lower long-term risk of death was present in all patients undergoing transplantation, irrespective of their age group or primary renal disease. Similar results were seen when survival with a transplant was censored for graft failure. The projected life expectancy with a transplant was 17.19 yr compared with only 5.84 yr on dialysis. Despite an initial higher risk of death, long-term survival for patients who undergo transplantation is significantly better compared with patients who are listed but remain on dialysis. A successful transplant triples the life expectancy of a listed renal failure patient.     

Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation.

BACKGROUND: Epidemiological data implicate that renal transplants from living unrelated donors result in superior survival rates as compared with cadaveric grafts, despite a higher degree of human lymphocyte antigen (HLA) mismatching. We undertook a center-based case control study to identify donor-specific determinants affecting early outcome in cadaveric transplantation. METHODS: The study database consisted of 152 consecutive cadaveric renal transplants performed at our center between June 1989 and September 1998. Of these, 24 patients received a retransplant. Donor kidneys were allocated on the basis of prospective HLA matching according to the Eurotransplant rules of organ sharing. Immunosuppressive therapy consisted of a cyclosporine-based triple-drug regimen. In 67 recipients, at least one acute rejection episode occurred during the first month after transplantation. They were taken as cases, and the remaining 85 patients were the controls. Stepwise logistic regression was done on donor-specific explanatory variables obtained from standardized Eurotransplant Necrokidney reports. In a secondary evaluation, the impact on graft survival in long-term follow-up was further measured by applying a Cox regression model. The mean follow-up of all transplant recipients was 3.8 years (SD 2.7 years). RESULTS: Donor age [odds ratio (OR) 1.05; 95% CI, 1.02 to 1.08], traumatic brain injury as cause of death (OR 2.75; 95% CI, 1.16 to 6. 52), and mismatch on HLA-DR (OR 3.0; 95% CI, 1.47 to 6.12) were associated with an increased risk of acute rejection, whereas donor use of dopamine (OR 0.22; 95% CI, 0.09 to 0.51) and/or noradrenaline (OR 0.24; 95% CI, 0.10 to 0.60) independently resulted in a significant beneficial effect. In the multivariate Cox regression analysis, both donor treatment with dopamine (HR 0.44; 95% CI, 0.22 to 0.84) and noradrenaline (HR 0.30; 95% CI, 0.10 to 0.87) remained a significant predictor of superior graft survival in long-term follow-up. CONCLUSIONS: Our data strongly suggest that the use of catecholamines in postmortal organ donors during intensive care results in immunomodulating effects and improves graft survival in long-term follow-up. These findings may at least partially be explained by down-regulating effects of adrenergic substances on the expression of adhesion molecules (VCAM, E-selectin) in the vessel walls of the graft.     

Effect of the shipment of cadaveric renal allografts on allograft survival.

BACKGROUND: Since 1996, the allocation of grafts in France has been based on a hierarchical three-level system: national, regional and local. The objective of this study was to determine whether the shipment of cadaveric kidneys according to these new exchange rules affects allograft outcome in the Eastern region of France. METHODS: This retrospective study analysed all renal transplants performed in the four centres of the French Eastern region during 3 years (1996 to 1998). All patients were followed up until death, return to dialysis, last information date or the end of June 2003. Information regarding the donors, recipients and treatments, as well as patient and graft outcome, was recorded. Factors associated with graft loss were analysed using Cox proportional hazard methods. RESULTS: 542 transplants were analysed, 287 (53%) kidneys were transplanted locally, 229 (42.2%) kidneys coming from exchanges within the region and 26 (4.8%) from another region. There were statistically significant differences between the four centres for donors' and recipient' characteristics and for immunosuppressive treatment, but there was no difference between centres regarding patient survival (94.4% at 5 years), graft survival (83.7% at 5 years) or death-censored graft survival (87.8% at 5 years). Compared to locally transplanted grafts, shipped grafts had significantly better human leukocyte antigen (HLA) matching (2.5 +/- 1.3 versus 2.1 +/- 1.0 matches, P = 0.0005 but a longer cold ischaemia time (23.2 +/- 7.9 versus 19.2 +/- 7.8 h, P < 0.0001). Three independent factors were associated with a reduced graft survival: at least one acute rejection, delayed graft function and a shipped graft. CONCLUSION: The results of this study suggest that the shipment of cadaveric renal allografts in a regional distribution system is associated with better HLA matching but is a significant predictor of graft loss at 5 years. It would be advisable to restrict graft sharing to patients whose access to transplantation is limited, taking special care to avoid any additional factors having a detrimental effect on the outcome.     

Failure of B-cold lymphocytotoxins to enhance cadaveric renal allograft survival

In a three-year period between January 1980 and December 1982, 242 consecutive cadaver transplant recipients in one center were tested before transplantation by cytotoxicity against a random panel of T and B lymphocytes at 5 degrees C and 37 degrees C incubation. They were also tested for HLA-A, B, and DR antigens. Kidney transplants were carried out with the primary objective of achieving a two-DR match. Kidney transplants were carried out only in the absence of T-warm positive cross-matches. All patients were followed for a minimum period of one year after transplant. There have been no exclusions, and all causes of failure, including death, have been counted as graft losses. Patients were stratified according to HLA-A, B, and DR matches and were also divided into high-antibody and low-antibody groups. The recipients with no antibodies had the best one-year graft survival (66%). Recipients with B-cold antibodies did not have enhanced one-year graft survival (51%). Recipients with B-warm antibodies did indifferently (56%). The worst results were seen in recipients who had pretransplant T-warm antibodies (42%) though the number of patients in this group was small.     

环孢素新剂型Neoral在肾移植中的应用

对10例肾移植患者作山地明转换Neoral试验进行药效动力学对比研究，30例新移植患者应用Neoral进行临床观察。结果表明，Neoral最高血浓度（Cmax）较山地明高282±84ng／ml，达峰时间（Tmax）短0．79±0．29h，CSA暴露（AUC）大1533±169ng／（h·ml）（P＜0．05）。提示Neoral有较好地抗排斥反应作用，但由于吸收迅速，血药浓度易超过治疗窗水平而引起毒副反应。本组肝中毒达20％。认为Neoral与山地明转换比例应为1：0．8～1：0．9，以避免毒副作用发生；Neoral服药量可较山地明常规剂量减少25％。     

Influence of early function on long-term pediatric cadaveric renal allograft survival

The significance of early renal graft function on long-term transplant survival is controversial. From our pediatric renal transplant population we studied 151 children who had an initial cadaveric renal transplant, were dependent on dialysis before transplantation and were 5 to 19 years old at transplantation. We used dependence upon dialysis as the parameter for early graft function. There was a statistically significant difference in long-term graft survival between patients who were independent of and dependent on dialysis at 1 week and 1 month postoperatively. Our results show that early renal graft function is important for long-term graft survival. All efforts should be directed to obtaining early renal graft function by proper organ procurement, storage, operative technique and aggressive postoperative management.     

Immunologic factors: the major risk for decreased long-term renal allograft survival

BACKGROUND: Both antigen-dependent (immunologic) and non-antigen-dependent (nonimmunologic) factors have been implicated in long-term renal allograft loss. Differentiating between these two factors is important because prevention strategies differ. METHODS: To isolate the importance of these 2 factors, we studied long-term actuarial graft survival in a cohort of adult kidney recipients who underwent transplants at a single institution between January 1, 1984 and October 31, 1998. Excluded were recipients with graft loss as a result of death with function, technical failure, primary nonfunction, and recurrent disease, leaving 1587 recipients (757 cadaver [CAD], 830 living donor [LD]) who would be at risk for graft loss secondary to both immunologic and nonimmunologic factors. These recipients were analyzed in the following 2 groups: those treated for a previous episode of acute rejection (AR) (Group1; n = 588; 328 CAD, 260 LD) and those with no AR (Group 2: n = 999; 429 CAD, 570 LD). Actuarial graft survival and causes of graft loss were determined for each group. Presumably, graft loss in Group 1 would be caused by immunologic and nonimmunologic factors; graft loss in Group 2 would be caused primarily by nonimmunologic factors. RESULTS: The 10-year graft survival rate (censored for death with function, technical failure, primary nonfunction, and recurrent disease) in Group 2 was 91%. In contrast, the 10-year graft survival rate in Group 1 was 45% (P<0.001 vs. Group 2). Causes of graft loss in Group 2 were chronic rejection in 1.8% (3.0% CAD, 0.9% LD), de novo disease, 0.4%; sepsis, 0.2%; discontinuation of immunosuppressive therapy, 0.3%; and unknown, 0.6%. In contrast, 23.8% (29.9% CAD, 16.2% LD) of recipients in Group 1 had graft loss caused by chronic rejection (P = 0.001 vs. Group 2). CONCLUSIONS: This very low incidence of chronic rejection in recipients without previous AR suggests that immunologic factors are the main determinants of long-term kidney transplant outcome; nonimmunologic factors in isolation may have only a minimal impact on long-term graft survival.     

Identifying risk factors in renal allografts before transplant: machine-measured renal resistance and posttransplant allograft survival

Enhancement of renal allograft function and survival in an era where expanded criteria donors are increasingly used requires validated selection criteria. The goal of this retrospective study was to evaluate the significance of pretransplant donor and allograft parameters to identify risk factors that can be used in a model to predict 1-year allograft outcomes. Donor demographic factors, donor type, and allograft parameters such as biopsy results and machine-measured renal resistance were correlated with 1-year graft outcome. The Kaplan-Meier method was used to estimate graft survival using the categorical predictors of donor type, donor age, and machine measured renal resistance at 1.5, 3, and 5 hours. The log-rank test was used to test the difference in survival curves between cohorts. The Cox regression analysis was used to estimate hazard ratios for machine-measured renal resistance, donor age, donor terminal creatinine level, donor's estimated glomerular filtration rate, cold ischemia time, and percent glomerulosclerosis. The data show that machine-measured renal resistance at 3 and 5 hours has a statistically significant inverse relationship to 1-year graft survival. All other risk factors had no correlation with 1-year graft survival. The machine-measured renal resistance at 3 hours is the earliest significant predictor of 1-year allograft outcome.     

Analysis of prognostic factors affecting renal allograft survival

A total of 201 consecutive cadaveric kidney transplantations were performed in 188 patients at the Chinese Great Wall Hospital, Beijing, from October 1977 to May 1990. The overall 1-, 2-, 5-, and 10-year graft survival rates were 75.5%, 64.5%, 37.0%, and 32.9%, respecitively. In the last 5 years, these figures have risen to 83.7% at 1 year, 69.5% at 2 years, and 40.8% at 5 years, respectively. The 14 variables correlating to graft survival in the present study were analyzed using the log rank test for univariate analysis and the Cox proportional hazard model for multivariate analysis. The results show that immunosuppressive drug therapy, cold ischemia time, acute tubular necrosis, and infection were significant factors affecting the survival of cadaveric kidney grafts. Triple therapy with low-dose cyclosporin, as compared to conventional immunosuppressive drug therap, significantly increased the 1-year graft survival rate (90.3% vs 31.3%) but did not influence the long-term graft survival rate after 3 years. The incidence of acute tubular necrosis significantly correlated to the cold ischemia time and influenced the 1-year graft survival. Analysis showed that the lymphocytotoxic crossmatch affected graft survival after 3 years and that most late graft losses were due to chronic rejection, suggesting that histocompatibility is the strongest factor affecting long-term graft survival. A beneficial effect of pretransplant blood transfusions on long-term graft survival was seen in patients treated with conventional immunosuppressive drugs but not in cyclosporin-treated patients.     

Time dependency of factors affecting renal allograft survival

The function of renal transplants can deteriorate at any time posttransplant, but the risks and mechanisms may differ at different times posttransplant. Survival of 522 consecutive cadaveric renal transplant recipients followed for at least 6 mo were analyzed, with patient death censored. The overall risk factors in univariate analysis were acute rejection requiring antibody therapy (AR), delayed graft function, elevated serum creatinine at 6 mo, high panel-reactive antibodies, and donor age > or =55 yr, with borderline effects of recipient age and female gender. These risks were studied in each of three intervals posttransplantation: < or =6 mo, 6 mo to 5 yr, and >5 yr. Of the 135 graft failures, 53 occurred < or =6 mo, 61 between 6 mo and 5 yr, and 21 beyond 5 yr. By multivariate analysis. the risks for graft failure in interval < or =6 mo were AR (hazard ratio (HR) = 4.86, P < 0.001); delayed graft function (HR = 1.47, P = 0.06): and high panel-reactive antibodies (HR = 2.04, P = 0.0(3). Between 6 mo and 5 yr, the risks for graft loss were AR (HR = 2.87, P < 0.001) and serum creatinine at 6 mo > or =150 micromol/L (HR = 3.69, P < 0.001). Beyond 5 yr the risk factors were donor age > or =55 yr (HR = 5.87, P = 0.002), with a borderline effect of kidneys from female donors (HR = 2.28, P = 0.07). HLA-A, -B, and -DR matching and presensitization had most of their effect through early AR and impaired function. The results indicate that risks for graft loss are time-dependent: early losses correlate with injury and rejection, but late events correlate with donor age and possibly workload.