移植肾慢性排斥反应患者治疗前后24h尿蛋白定量、血肌酐及血压水平变化研究

目的 探讨移植肾慢性排斥反应患者治疗前后24h尿蛋白定量、血肌酐及血压水平变化情况.方法 选取行肾移植术后发生移植肾慢性排斥反应的70例患者为实验组,并选取同期行肾移植术后不伴移植肾慢性排斥反应的正常患者70例为对照组.对于发生排斥反应的患者给予冲击治疗和调整免疫抑制剂的剂量逆转排斥反应.将两组患者行肾移植术后的和出院前的24h尿蛋白定量、血肌酐及血压进行研究比较.结果 经研究发现,治疗前实验组的24h尿蛋白定量、血肌酐及血压水平明显高于对照组,治疗后降低为基本正常,有显著性差异或有非常显著性差异(P＜0.01).结论 移植肾慢性排斥患者的24h尿蛋白定量、血肌酐及血压水平变化呈现一定的规律性,抗排斥反应治疗可大大改善其水平.研究证明24h尿蛋白定量、血肌酐及血压水平对移植肾慢性排斥反应的临床诊断和治疗具有重要价值.     

CD44在大鼠肾移植急性排斥反应中的表达

目的:探讨移植肾组织CD44的表达及血清中可溶性CD44的含量与急性排斥反应的关系。方法:雄性Wistar大鼠和SD大鼠分别作为供体和受体,共分为四组,采用改进的Blom法大鼠原位肾移植模型。免疫组织化学染色法检测移植肾组织CD44分子的表达;酶联免疫吸附试验测定术后血清中可溶性CD44水平的变化。结果:移植肾组织CD44分子的表达在同种异体移植组显著高于同品系移植组、手术对照组及药物治疗组(均P<0.05);移植肾组织CD44分子的表达与急性排斥反应呈正相关(皮质:r=0.734,髓质:r=0.670,均P<0.01);发生急性排斥反应的移植肾组织CD44分子的表达与Banff急性排斥反应指数无相关性(P>0.05);血清中可溶性CD44分子各组间差异无统计学意义,与急性排斥反应及Banff指数均无相关性(均P>0.05)。结论:CD44分子在肾移植急性排斥反应的发病机制中起着重要作用,为进一步提高移植排斥反应防治水平提供理论依据。     

排斥反应时血清可溶性白细胞相关免疫球蛋白样受体1的水平及意义

目的 探讨可溶性白细胞相关免疫球蛋白样受体1(sLAIR-1)与移植物排斥反应的相关性.方法 采用双抗体夹心酶联免疫吸附试验测定23例肝移植、139例肾移植患者的血清sLAIR-1水平,并以健康志愿者为对照.结果 健康志愿者的血清sLAIR-1水平为(4.3±2.3)μg/L,移植器官功能正常者(肝移植11例,肾移植87例)的sLAIR-1为(6.3±3.7)μg/L,二者比较,差异无统计学意义(P>0.05).肝移植后发生急性排斥反应的6例患者,其血清sLAIR-1水平为(47.2±25.9)μg/L;肾移植后后发生急性排斥反应的20例患者,其血清sLAIR-1水平(36.3±14.7)μg/L;移植肾功能丧失的5例患者,其血清sLAIR-1水平为(28.8±9.4)μg/L,上述三者的血清sLAIR-1水平均明显高于移植物功能正常者和健康志愿者(P<0.01).移植肝重度排斥反应的1例,其血清sLAIR-1高达117.3μg/L,为正常人的27倍.移植肝慢性排斥反应者(5例)和移植肾慢性排斥反应者(27例)的血清sLAIR-1水平分别为(16.1±6.4)μg/L和(13.1±5.5)μg/L,也明显高于移植物功能正常者和健康志愿者(P<0.05).结论 发生排斥反应者的血清sLAIR-1水平升高,其水平的升高可能是发生排斥反应的重要风险因素.     

异种肾移植超急性排斥反应时血液流变学的变化

采用猪-犬肾移植建立超急性排斥反应模型，以研究此时的血液流变学变化。分别在移植前、移植肾超急性排斥发生时和排斥肾切除后10～15分钟检测外周血的血液流变学参数变化。结果异种肾移植发生超急性排斥时，血小板聚集显著增高，移植肾切除后血中的血小板数和纤维蛋白原明显下降，血小板聚集也恢复原有水平。提示血小板、纤维蛋白原参与了异种移植超急性排斥反应的发生过程，而血小板聚集可能是诊断异种移植超急性排斥反应一个有价值的指标。     

丙型肝炎病毒感染对肾移植受者排斥反应及人/肾存活率的影响

目的 研究丙型肝炎病毒(HCV)感染是否影响移植肾急性和慢性排斥反应的发生率,以及受者和移植肾的存活率.方法 对1992年6月至2004年6月所行肾移植的495例受者进行了随访,其中术前HCV抗体阳性受者27例(HCV阳性组),随机抽取HCV抗体阴性受者27例作为对照组,行组间配对研究,分析HCV感染状态对肾移植受者急性和慢性排斥反应发生率以及人/肾存活率的影响.结果 HCV阳性组受者急性排斥反应的发生率显著高于对照组(19.14%和6.38%,P<0.01),HCV阳性组慢性排斥反应的发生率也明显高于对照组(23.40%和12.76%,P<0.01),对照组肾移植后1、3、5年人/肾存活率显著高于HCV阳性组,差异有统计学意义(P<0.01).结论 HCV感染可以明显增加肾移植受者急性和慢性排斥反应的发生率,降低人/肾存活率.     

抑制性受体CD305表达在移植肾排斥反应监测中的意义

目的 探讨抑制性受体CD205的表达在移植肾排斥反应中的意义.方法 应用双单克隆抗体夹心ELISA法检测153例肾移植术后患者血清中可,溶型CD305(sCD305)的表达水平,20例健康志愿者标本作为对照组.结果 对照组和98例移植肾功能正常患者血清sCD305表达分别为(4.3±2.3)和(6.3±3.7)μg/L.20例移植肾急性排斥及5例移植肾失功患者血清sCD205表达明显增加,分别为(36.3±14.7)和(28.8土9.4)μg/L,显著高于对照组和移植物功能正常组(P＜0.01).30例移植.肾慢性排斥及6例尿毒症透析患者血清sCD205分别为(13.1±5.5)和(11.2±4.6)μg/L,亦明显高于对照组和移植肾功能正常组(P=0.00).结论 发生移植肾排斥反应的患者血清sCD3205有较高水平的表达,可望作为移植肾排斥反应的监测指标之一.     

肾移植排斥反应移植物中基因表达的研究

移植肾急性排斥是同种异体肾脏移植主要的临床问题 ,是慢性移植肾失功能的主要危险因素。监测血清肌酐水平、应用免疫组织化学方法或病理检查来诊断急性排斥、预测慢性排斥的发生不是很敏感 ,也不是很可靠。目前 ,人们应用分子生物学的技术方法来研究试验动物移植物和临床病理组织标本中与排斥有关的基因及其表达产物来筛选标志性基因 ,有望对肾移植排斥反应做出早期诊断并预测其发生 ,进而为阐明移植物排斥的机理以及基因治疗指明方向     

血清可溶性血管细胞粘附分子-1测定在肾移植急性排斥反应中的临床意义

目的:探讨血清可溶性血管.细胞粘附分子-1(sVCAM-1)测定在肾移植术后免疫学监测中的价值.方法:采用酶联免疫吸附法(ELISA)动态监测56例肾移植患者术后sVCAM-1水平的变化.结果:肾移植患者术后sVCAM-1水平呈规律性变化,急性排斥反应组sVCAM-1水平明显高于移植肾功能稳定组和CsA肾中毒组,差异有非常显著意义(P＜0.01).对激素治疗敏感的排斥反应患者,sVCAM-1逐渐降至正常水平;耐激素的排斥反应患者应用ATG治疗后,sVCAM-1在排斥反应后1个月内仍维持在较高水平.CsA肾中毒组sVCAM-1水平无明显变化.结论:肾移植术后动态监测sVCAM-1水平的变化,有助于急性排斥反应的诊断、鉴别诊断及指导临床治疗.sVCAM-1可以作为肾移植术后急性排斥反应的免疫学监测指标.     

肾移植慢性排斥反应的研究进展

肾移植术后的慢性排斥反应主要表现为肾小球滤过率渐进性下降,血肌酐缓慢上升,常伴有蛋白尿(>1.0g/24h)和高血压,症状继续加重,肾功能恶化,是移植肾丧失功能的重要原因。术后第1年开始,每年10%～15%的患者发生不可逆的移植肾功能丧失,术后5年内最终因慢性排斥反应导致移植...     

BNP及NT-proBNP在鉴别同种异体肾移植术后患者急性排斥反应中的早期辅助诊断价值

目的探讨同种异体肾移植术后患者发生急性排斥反应时血浆B型钠尿肽(BNP)、B型钠尿肽氨基末端前体(NT-proBNP)的浓度变化及早期的辅助诊断价值。方法选择在我院行首次同种异体肾移植术患者术后发生急性排斥反应12例为实验组(A组),并随机选择同期未发生急性排斥反应17例为对照组(B组)。回顾性分析两组患者血浆B型钠尿肽及其氨基末端前体浓度、血肌酐(SCr)水平、尿量及左心室舒张末期内径(LVDD)、舒张早期与心房收缩期二尖瓣血流峰速比值(E/A)、射血分数(LVEF)的变化,进行统计学比较。结果急性排斥反应组比较非急性排斥反应组同期BNP、NT-proBNP增高发生率高于尿量减少的发生率、SCr增高及左室结构及功能指标改变的发生率(P0.01),且急性排斥反应时BNP、NT-proBNP增高早于SCr,NT-proBNP与BNP比较增高幅度更大、发生更早。结论肾移植术后发生急性排斥反应时血BNP、NT-proBNP浓度早期显著增高,血BNP、NT-proBNP浓度变化可作为早期辅助诊断移植肾急性排斥反应发生的敏感指标,其中NT-proBNP更敏感。     

Prevalence and association of post-renal transplant anemia

In some renal allograft recipients, anemia persists or develops following transplantation. Anemia is associated with pre-operative blood loss and allograft dysfunction, including delayed graft function, acute rejection and chronic allograft dysfunction. To study the prevalence and association of post-renal transplant anemia, we studied 200 renal transplant recipients; 131 (65.5%) patients were males and 69 (34.5%) patients were females, and age ranged from 17 to 67 years, with a mean of 37.7 ± 10.8 years. All patients were receiving cyclosporine, prednisolone and mycophenolate mofetil (MMF). Complete blood count was done at two times: three and six months post-renal transplant. There were 74% anemic patients three months after renal transplantation and 45% anemic patients six months after renal transplantation. High creatinine value, female gender, delayed graft function, episodes of acute rejection, perioperative blood loss and infections were the only significant independent risk factors for prevalence of anemia post-renal transplant. In our study, we did not find an association between MMF and cyclosporine nor angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptors blocker (ARBs) with anemia. This study demonstrates that anemia is a common complication during the first six months after kidney transplantation, with several risk factors precipitating this complication.     

Long-term beneficial effect of tacrolimus conversion on renal transplant recipients

OBJECTIVE: Acute rejection, chronic allograft nephropathy, and cyclosporine (CsA) toxicity remain serious problems for renal transplant recipients and may lead to graft loss. We retrospectively analyzed 34 patients whose biopsies revealed acute and/or chronic allograft rejection, or CsA nephrotoxicity, and who converted from CsA to tacrolimus. PATIENTS AND METHODS: From July 1996 through September 2003, CsA was converted to tacrolimus in 34 renal transplant recipients (26 male, 8 female) with renal biopsy at our hospital. Blood pressure and serum creatinine levels were checked monthly and serum cholesterol, triglyceride, and glutamic-pyruvic transaminase (GPT) levels were checked every three months. RESULTS: A consistently stable and better function after conversion was obtained in a significant portion (24, 71%) of patients. A statistically significant decline in serum creatinine and an improvement in the glomerular filtration rate were found at 3 m, 6 m, 12 m, 36 m, and 72 m after tacrolimus conversion. In 85.7% (12/14) of patients with acute rejection and in 35.7% (5/14) of patients with chronic allograft nephropathy (concomitant with acute rejection in 5), improved or stabilized graft function was noted. In addition, the systolic blood pressure and diastolic BP dropped significantly (P<0.05), while there was no significant change in cholesterol, triglyceride, and GPT levels. CONCLUSION: The beneficial effect of tacrolimus conversion on patients with acute rejection, chronic allograft nephropathy, or CsA nephrotoxicity was demonstrated in long-term follow up. The improvement in both renal function and blood pressure may be of paramount importance in reducing long-term cardiovascular morbidity and mortality.     

The role of C-reactive protein in graft dysfunction after renal transplantation

PURPOSE: We investigated whether serial daily measurements of serum C-reactive protein could help differentiate episodes of transplant dysfunction due to rejection, infection, cyclosporin A nephrotoxicity or acute tubular necrosis in renal allograft recipients. MATERIALS AND METHODS: Morning serum was obtained daily from 134 patients during the first 30 days after renal transplantation. All episodes of graft dysfunction were recorded and compared to transplant biopsies. C-reactive protein concentrations were correlated with postoperative graft function and the various causes of graft dysfunction. RESULTS: All patients demonstrated an increase in C-reactive protein in response to surgery and a maximum level was reached on day 2 after transplantation. Mean C-reactive protein concentration was significantly increased for delayed (61.50 microg./ml.) compared to primary (mean 38.01) graft function (p = 0.001, Mann-Whitney U test). There were significant increases in C-reactive protein for bacterial infections other than asymptomatic bacteriuria (33.98 microg./ml), interstitial graft rejection (16.43) and acute tubular necrosis (30.50) compared to uneventful courses. C-reactive protein was unchanged for viral infections or cyclosporin A toxicity. CONCLUSIONS: Serial C-reactive protein measurements help to identify renal transplant dysfunction of different origins. However, rejection, infection and acute tubular necrosis show similar patterns of C-reactive protein increase. Thus, C-reactive protein is unable to discriminate the causes of renal graft dysfunction. Biopsy remains the gold standard for the differential diagnosis of renal allograft dysfunction.     

The safety and efficacy of early withdrawal of calcineurin inhibitors in kidney transplant recipients 6 months' posttransplant

INTRODUCTION: The introduction of calcineurin inhibitors (CNIs) in clinical transplantation has resulted in dramatic reduction in acute rejection rate and improvements in short-term allograft survival. However, CNI-induced chronic nephrotoxicity is a clinical concern since it is a major cause of chronic allograft failure. Recent studies suggest that withdrawal or reduction of CNI dosage results in improvement in graft function and survival. The aim of this study was to evaluate the safety and efficacy of substituting CNIs with mycophenolate mofetil (MMF) at 6 months' postkidney transplant. METHODS: Kidney transplant recipients of first or second grafts (n = 20) maintained on CNI-based therapy and with no history of irreversible acute or vascular rejection were included in the study. Primary end points were the incidence of biopsy-proven acute rejection or treatment failure. Secondary end points included changes in mean serum creatinine and estimated GFR (Cockroft and Gault, CG) over time, incidence of infection, cardiovascular risk factors (blood pressure, cholesterol), graft and patient survival rates, as well as incidence of biopsy-proven chronic allograft nephropathy (CAN). Study patients were compared to a matched control group (n = 20) who remained on CNI-based therapy at equivalent time points. RESULTS: Incidence of acute rejection following CNI withdrawal was 15%. All episodes reversed with steroid pulses. There was no significant difference in mean serum creatinine or estimated GFR during the follow-up period. No significant change occurred in blood pressure or antihypertensive agents between the groups; however, there was a trend toward lower cholesterol levels after CNI withdrawal. No graft or patient loss was seen during the study period. Biopsy-proven CAN was diagnosed in 2 control patients (10%) at 6 to 8 months' posttransplant. CONCLUSIONS: Withdrawal of CNI at 6 months following kidney transplantation is associated with an increased risk of rejection and a trend toward lower serum creatinine and cholesterol levels. Further follow-up is needed to establish the long-term results of CNI-sparing regimens on the development of CAN.     

Microchimerism and renal transplantation: doubt still persists

OBJECTIVE: We sought to study microchimerism in a group of kidney transplant recipients. MATERIALS AND METHODS: In this study, the peripheral blood microchimerism (PBM) after renal transplantation was retrospectively evaluated in 32 male-to-female recipients of living unrelated or cadaveric donor renal transplants. Using a nested polymerase chain reaction (PCR) amplification specific for SRY region of the Y chromosome, microchimerism was detected with a sensitivity of 1:1,000,000. Recipients were compared according to the presence of PBM, acute and chronic rejection episodes, type of allotransplant, recipient and donor age at transplantation, previous male labor or blood transfusion, allograft function (serum creatinine level), and body mass index. RESULTS: Among 32 recipients, 7 (21.9%) were positive for PBM upon multiple testing at various posttransplant times. All microchimeric recipients had received kidneys from living unrelated donors. No significant difference was observed with regard to other parameters. In addition the acute rejection rate in the microchimeric group was 3 (42%) versus 4 (16%) in the nonmicrochimeric recipients (not significant). CONCLUSION: Our results suggested better establishment of microchimerism after living donor kidney transplantation. However, doubt persists concerning the true effect of microchimerism after renal transplantation. It seems that microchimerism alone has no major protective role upon renal allograft survival.     

Stable kidney function in the second decade after kidney transplantation while on cyclosporine-based immunosuppression

BACKGROUND: Calcineurin inhibitors (CNIs) have been the mainstay of immunosuppressive protocols in kidney transplantation over the past 20 years. However, in some recipients, the adverse effects of CNIs contribute to chronic allograft nephropathy and death with function--the two leading causes of late graft loss. Other recipients maintain stable graft function. METHODS: We studied the impact of continuing CNI-based immunosuppression in the second decade after kidney transplantation. From 1984 through 1996, a total of 1,263 patients underwent a primary kidney transplant at the University of Minnesota and received cyclosporine-based immunosuppression. Antibody induction was used only in deceased donor recipients. RESULTS: The actuarial 20-year patient survival rate was 38%; graft survival, 30%; and death-censored graft survival, 60%. The annual mean serum creatinine level for recipients whose grafts survived > or =1 year remained stable, although recipients with a history of > or =1 acute rejection episode had a higher serum creatinine level vs. recipients who were rejection-free. The annual mean calculated creatinine clearance was also stable over time. In addition, for recipients who were acute rejection-free, chronic allograft nephropathy/chronic rejection was only responsible for 9% of graft losses. CONCLUSIONS: Our study suggests that some kidney transplant recipients tolerate long-term CNI-based immunosuppression with stable creatinine levels. Identifying certain recipients' predisposition to CNI toxicity and individualizing immunosuppressive therapy may be important in order to improve long-term kidney function, while simultaneously preserving low short-term acute rejection rates.     

Enzyme Linked Immunosorbent Spot (ELISPOT) Assay for Interferon-Gamma Independently Predicts Renal Function in Kidney Transplant Recipients

Post-transplant monitoring of cellular immunity might be useful in predicting long-term outcomes of kidney transplant recipients. We used an enzyme linked immunoabsorbent spot (ELISPOT) assay to serially measure the frequency of peripheral blood lymphocytes producing interferon-gamma in response to stimulator cells from donors or third parties in 55 primary kidney transplant recipients. Mean frequencies measured during the first 6 months after transplantation correlated significantly with the serum creatinine concentration at both 6 and 12 months following transplantation. The mean frequencies were higher in patients with acute rejection than in those without acute rejection. Multiple regression analyses indicated that the correlations between the early ELISPOT measurements of interferon-gamma and serum creatinine were independent of acute rejection, delayed graft function, or the presence of panel reactive antibodies before transplantation. Patients with low mean frequencies of interferon-producing cells in the early post-transplant period were generally free from acute rejection and exhibited excellent renal function at 6 and 12 months post-transplant. In conclusion, using the ELISPOT assay, we show an independent correlation between early cellular alloreactivity and long-term renal function. Increased levels of early alloreactivity measured with this assay may serve as a surrogate for chronic allograft dysfunction.     

Withdrawal of mycophenolate mofetil in stable renal transplant recipients

BACKGROUND: Mycophenolate mofetil (MMF) has been demonstrated to decrease episodes of acute rejection in renal transplant recipients during the first year after transplantation. The utility of MMF after 1 year is less clear. METHODS: Forty-five stable renal transplant recipients on maintenance therapy of cyclosporine microemulsion, MMF, and prednisone had MMF withdrawn at approximately 1 year after transplantation. A matching concurrent group of 45 stable renal transplant recipients served as the case control group. RESULTS: Two of 45 patients in the MMF withdrawal group suffered an acute rejection episode as opposed to 1 of 45 in the control group. Both patients who rejected in the withdrawal group had adequate cyclosporine levels and had no recent decrease in prednisone dose. There was no evidence of an increased incidence of proteinuria or increased creatinine levels in the MMF withdrawal group. CONCLUSION: In general, withdrawal of MMF in stable renal transplant recipients is well tolerated. No increased risk of rejection could be demonstrated in this patient group. A larger study will be needed to confirm our result.     

Comparison of transplanted kidney function in patients on two different doses of mycophenolate mofetil

INTRODUCTION: Mycophenolate mofetil (MMF), an immunosuppressant that is widely used in renal transplant recipients, is associated with several dose-dependent hematologic and gastrointestinal side effects that lead to drug dose reduction or even discontinuation. The aim of this study was to compare the renal function and acute rejection rates of kidney allograft recipients who were on two different mycophenolate mofetil doses. METHODS: In a prospective study, 59 allograft kidney recipients who were on MMF 2 g/d were randomly selected and followed for evidences of acute rejection or drug side effects. Four patients were excluded from the study due to noncompliance, graft loss, and patient loss from opportunistic infection. Of the remaining 55 patients, 22 patients (40%) underwent MMF dose reduction to 1.35 +/- 0.23 g/d due to perceived side effects or economic reasons (group 1). The mean time for this change was 4.2 +/- 2.1 months after the kidney transplantation. The remaining patients (group 2, n = 33, 60%) had no change in MMF 2 g/d drug dosage. All patients were followed for at least 30 months after transplantation. Renal function tests (blood urea and serum creatinine) were measured monthly. Statistical analysis was performed using SPSS 11.0 (Student t test). A P value < .05 was considered significant. RESULTS: The two groups were comparable regarding age, gender, other immunosuppressive medications, and the time after transplantation. There were no episodes of acute rejection in group 1 after MMF dose reduction. The renal function (blood urea or serum creatinine levels) was comparable between the two groups at the end of study (P = .846 and .610, respectively). CONCLUSION: MMF dose reduction was not associated with an increased risk of acute renal allograft rejection or impaired graft function.     

Delayed acute rejection episodes in cyclosporine-treated renal transplant recipients.

Of 109 cyclosporine-treated cadaveric renal allograft recipients, 45 were free of acute rejection in the first 4 weeks after transplantation. Eleven of 45 (24%) subsequently had delayed, biopsy-proven first rejection episodes 34-61 days after grafting, often after discharge from the hospital. Delayed rejectors had significantly higher plasma creatinine levels at all times during the first posttransplant month than 34 nonrejectors. Trough serum cyclosporine levels were similar in the two groups, although by the 4th week oral cyclosporine dose was significantly lower in the delayed rejection group. Two-thirds of those patients who had serum creatinine levels greater than or equal to 260 mumol/l at 2 weeks and greater than or equal to 225 mumol/l at 3 weeks had a delayed acute rejection episode. Renal transplant recipients treated with cyclosporine who have serum creatinine levels at or above these levels should be aggressively worked up and closely followed for the development of delayed acute rejection.