血浆粘附分子GMP－140测定在肾移植中的意义

随机选择６４例肾移植患者采用酶联免疫吸附法检测其血浆粘附分子ＧＭＰ－１４０水平，以探讨肾移植患者血浆ＧＭＰ－１４０水平的变化及意义。结果环孢素肾中毒组的血浆ＧＭＰ－１４０水平中度升高（２９２±９９μｇ／Ｌ），与移植肾功能稳定组比较（１１４±３０μｇ／Ｌ）差异显著（Ｐ＜０．０１）；排斥组（５１５±１８７μｇ／Ｌ）与稳定组及环孢素肾中毒组比较，差异显著（Ｐ＜０．０１）；肾功能稳定但并发感染者血浆ＧＭＰ－１４０水平（５３５±１７２μｇ／Ｌ）与急性排斥组比较差异不显著。结果提示测定血浆ＧＭＰ－１４０的变化对肾移植术后的监测具有一定的意义。     

移植肾急性排斥时血栓素A2、前列环素代谢改变及其对肾小球滤过率的影响

用放射免疫法检测２１例移植肾急性排斥时，肾移植患者尿液以及血浆血栓素Ｂ２（ＴＸＢ２）和６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ－ＰＧＦ１α）浓度，并检测４例不可逆急性排斥和７例慢性排斥移植肾切除后肾组织ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１α含量。发现急性排斥出现时，尿中ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１α含量均明显升高，ＴＸＢ２增多出现较早；血浆ＴＸＢ２浓度也显著增加，６－ｋｅｔｏ－ＰＧＦ１α浓度下降。尿液和血浆中ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值增大。正常肾组织标本中，肾髓质ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１α含量为皮质的４～５倍，皮髓质中ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值水平相同。不可逆急性排斥肾组织中，肾皮质ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值明显高于髓质。急性排斥时，尿液中ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１α比值变化与肾皮质平行。分析表明，急性排斥时，尿液ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值增大和移植肾肾小球滤过率负相关。     

同种异体肾移植患者血清SIL－2R水平变化及其临床意义

作者采用双抗体夹心酶联免疫吸附法（ＥＬＩＳＡ）对２０例同种异体尸肾移植患者进行了８９例次可溶性白介素２受体（ＳＩＬ－２Ｒ）检查。结果表明：移植前明显高于正常对照组，Ｐ＜０．００１。移植后随着肾功能的恢复而接近正常，但仍轻度高于正常对照组，Ｐ＜０．０１。发生急性排斥反应时较稳定期明显升高，Ｐ＜０．００１，且其上升时间早于血肌酐上升２～７天。而发生环孢素Ａ肾中毒或急性肾小管坏死时，血清ＳＩＬ－２Ｒ水平则变化不明显，Ｐ＜０．０５。因此，ＳＩＬ－２Ｒ的测定可作为移植肾排斥反应诊断和鉴别诊断的重要非创伤性指标。     

移植肾急性排斥时血栓素A2,前列环素代谢改变及其对肾小球？…

用放射免疫法检测２１例移植肾急性排斥时，肾移植患者尿液以及血浆血栓素Ｂ２和６－酮－前列腺素Ｆ１α浓度，并检测４例不可逆急性排斥和７例慢性排斥移植肾切除后肾组织ＴＸＢ２和Ｙ－ｋｅｔｏ－ＰＧＦ１α含量。发现急性排斥出现时，尿中ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１α含量均明显升高，ＴＸＢ２增多出现较早；血浆ＴＸＢ２浓度也显著增加，６－ｋｅｔｏｐ－ＰＧＦ１α深度下降。     

肾移植患者术后早期血浆内皮素的变化

对３２例尸体肾移植患者术前及术后早期３个月的血浆内皮素－１（ＥＴ－１）浓度进行了动态观察，同时行前列腺素Ｅ－２（ＰＧＥ－２）、血栓素Ｂ－２（ＴＸＢ－２）与环孢素Ａ（ＣｓＡ）血浓度的测定及移植肾功能与血压的监测。ＥＴ－１、ＰＧＥ－２及ＴＸＢ－２均采用放射免疫法测定，ＣｓＡ血浓度采用多克隆抗体偏振免疫荧光法（ＴＤＸ）进行。结果显示：移植前患者的血浆ＥＴ－１平均浓度为１０．２７±０．５７ｐｇ／ｍｌ，移植后３个月各阶段的ＥＴ－１值均显著降低，平均浓度为４．６２±０．１４ｐｇ／ｍｌ。与此同时，血浆Ｃｒ和ＢＵＮ值以及收缩压、舒张压也呈现相似的变化，与移植前相比有非常显著性差异（Ｐ＜０．０１），且血浆ＥＴ－１浓度的变化与移植肾功能及血压密切相关。血浆ＥＴ－１浓度可作为肾移植术后的一项监测参考指标。     

肾移植患者血清α_1－微球蛋白和β_2－微球蛋白测定的临床价值

测定了４５例肾移植患者术后血清α１－微球蛋白（α１－ＭＧ）、β２－微球蛋白（β２－ＭＧ）的含量，结果表明，α１－ＭＧ与血清肌酐呈正相关，术后肾功能正常者α１－ＭＧ、β２－ＭＧ下降，但仍高于正常，术后排斥者及环孢素肾中毒者的α１－ＭＧ及β２－ＭＧ均明显升高。结果提示α１－ＭＧ是一项较β２－ＭＧ更为敏感的反映移植肾功能的指标。测定血清α１－ＭＧ对早期诊断肾移植后急性排斥及环孢素Ａ肾中毒具有一定的临床应用价值。     

抑肽酶抑制体外循环期间血小板激活反应

为研究体外循环期间抑肽酶对血小板激活的抑制，将４０例心脏手术病人随机分为对照组和观察组。观察组加抑肽酶于预充液中，取围术期５个时段检测血小板计数（ＰＴＣ）、血栓烷Ｂ２（ＴＸＢ２）、血小板表面α颗粒膜蛋白（ＧＭＰ１４０）、β血小板球蛋白（βＴＧ）、血小板第４因子（ＰＦ４）、５羟色胺（５ＨＴ）、术后出血量。结果表明对照组ＰＴＣ明显下降，ＴＸＢ２、ＧＭＰ１４０、βＴＧ、ＰＦ４、５ＨＴ均显著升高；观察组以上各项指标及术后出血量均较对照组明显好转（Ｐ＜０．０５或Ｐ＜０．０１）。作者认为，抑肽酶通过抗纤溶等作用可抑制体外循环期间血小板的激活，减少术后出血量。     

体外循环中止血芳酸对血小板的保护作用

目的：探讨止血芳酸在体外循环中对血小板的保护作用及其临床意义。方法：测定止血芳酸组和对照组血小板数量、出血量和输血量,及体外循环前后血浆α－颗粒膜蛋白（ＧＭＰ－１４０）,血栓烷Ｂ２（ＴＸＢ２）和６－酮－前列腺素Ｆ１a(6-k-PGF1a）的浓度变化。结果,体外循环术后血小板计数组明显高于对照组,出血量明显少于对照组。ＧＭＰ－１４０、ＴＸＢ２上升幅度小于对照组,二者相比差异显著（Ｐ＜０．０５）。结论：止血芳酸在体外循环术中可以起到保护血小板,减少术后出血的作用。     

肾移植后血清白细胞介素2、可溶性白细胞介素2受体和白细胞介素6的监测

动态监测６０例肾移植患者术后２个月内血清白细胞介素２（ＩＬ－２）、可溶性ＩＬ－２受体（ｓＩＬ－２Ｒ）和白细胞介素６（ＩＬ－６）的变化。结果发现发生急性排斥反应时，上述细胞因子的升高较临床诊断提早数天，并且显著高于环孢素Ａ肾中毒组；对甲泼尼龙敏感的排斥反应，抗排斥治疗数天后上述因子下降到排斥前水平。提示肾移植术后动态监测患者血清ＩＬ－２、ｓＩＬ－２Ｒ和ＩＬ－６有助于急性排斥反应的早期诊断、鉴别诊断、及时治疗和甲泼尼龙抗排斥的疗效评价。     

肾移植患者血内皮素和一氧化氮检测的临床意义

目的：探讨肾移植患者血中内皮素（ＥＴ）和一氧化氮（ＮＯ）的临床意义。方法：对３２例肾移植患者进行外周血ＥＴ－１和ＮＯ动态检测，将检测结果与对照组进行比较，并按移植肾状况和血压值再分别分组进行比较。结果：肾移植后ＥＴ－１值较对照组明显下降（Ｐ〈０．０５），ＮＯ值明显升高（Ｐ〈０．０１）；急性排斥反应发生时，ＮＯ值较正常和慢性排斥反应者升高（Ｐ〈０．０１），而发生慢性排斥反应时，ＥＴ－１值较肾功能正常     

Immunohistological analysis of renal allograft biopsies from cyclosporin-treated patients

Differentiation of cyclosporin nephrotoxicity from renal allograft rejection is often difficult. Induction of tubular HLA-class II antigens and elevated levels of leucocyte infiltration are associated with allograft rejection but their association with cyclosporin nephrotoxicity is unclear. In order to determine these relationships, transplant biopsies (n=32) from patients considered to have cyclosporin nephrotoxicity, allograft rejection or stable graft function were stained with monoclonal antibodies specific for HLA-class II antigens and infiltrating leucocytes. Leucocyte infiltration was elevated during rejection but not in cyclosporin nephrotoxicity or stable graft function. While HLA-class II antigen expression was induced in 71% of the biopsies obtained during clinical rejection, no increased expression was found in the other 29%. Induced antigens were detected in five of the nine biopsies obtained in the presence of cyclosporin nephrotoxicity 90 days after transplantation. In four of these, induction was attributed to prolongation of increased class II expression following previous rejection episodes. Thus, the presence of induced class II antigens in the renal allograft does not exclude a diagnosis of cyclosporin nephrotoxicity.     

Immunohistological analysis of renal allograft biopsies from cyclosporin-treated patients: Induced HLA-class II antigen expression does not exclude a diagnosis of cyclosporin nephrotoxicity

Abstract. Differentiation of cyclosporin nephrotoxicity from renal allograft rejection is often difficult. Induction of tubular HLA-class II antigens and elevated levels of leucocyte infiltration are associated with allograft rejection but their association with cyclosporin nephrotoxicity is unclear. In order to determine these relationships, transplant biopsies ( n =32) from patients considered to have cyclosporin nephrotoxicity, allograft rejection or stable graft function were stained with monoclonal antibodies specific for HLA-class II antigens and infiltrating leucocytes. Leucocyte infiltration was elevated during rejection but not in cyclosporin nephrotoxicity or stable graft function. While HLA-class II antigen expression was induced in 71% of the biopsies obtained during clinical rejection, no increased expression was found in the other 29%. Induced antigens were detected in five of the nine biopsies obtained in the presence of cyclosporin nephrotoxicity 90 days after transplantation. In four of these, induction was attributed to prolongation of increased class II expression following previous rejection episodes. Thus, the presence of induced class II antigens in the renal allograft does not exclude a diagnosis of cyclosporin nephrotoxicity.     

Combination fine-needle aspiration cytology and intrarenal manometry at the onset of renal dysfunction

Twenty-three consecutive cadaveric renal allograft recipients immunosuppressed with cyclosporin have been monitored three times a week by fine-needle aspiration cytology and intrarenal manometry until discharge from hospital or until 30 days post-transplant. Standard criteria were used to determine the cause of allograft dysfunction. The onset of allograft rejection was marked by an elevation of the total corrected increment score by fine-needle aspiration cytology in 80 per cent of rejection episodes whereas intrarenal pressure was raised in only 46.6 per cent. However, intrarenal pressure was greater than 40 mmHg on a single occasion in 16 measurements performed on allografts showing evidence of cyclosporin nephrotoxicity. By combining fine-needle aspiration cytology and intrarenal manometry the sensitivity of these tests for allograft rejection was increased to 93.3 per cent at the onset of renal dysfunction. Our results demonstrate that fine-needle aspiration cytology is more sensitive than intrarenal manometry as a single investigation. However, the combined test may have an important role in the differentiation of allograft rejection and cyclosporin nephrotoxicity in the early management of renal allograft recipients.     

Monitoring of serum neopterin levels in renal transplant recipients: increased values during impaired renal function and cytomegalovirus infection

In 92 renal transplant recipients, serum or plasma levels of neopterin were significantly elevated during pretransplant uremia, rejection, cyclosporin A induced nephrotoxicity and cytomegalovirus (CMV) infections. In patients with normal serum creatinine (less than 115 mumol/l) 71% had elevated serum neopterin levels. None of 19 cyclosporin A treated patients with stable renal function had a normal level of neopterin compared to 50% for patients treated with azathioprine (p less than 0.05). Due to the dependency on renal function the serum levels of neopterin could not distinguish between rejection and cyclosporin A induced nephrotoxicity. Marked increases in neopterin levels were seen during infections and especially during CMV infection. Determination of neopterin levels may be helpful in the diagnosis of CMV infection.     

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.     

肾移植术后血清IL—6水平的动态监测及临床意义

目的：观察肾移植术后发生急性排斥反应、感染、CsA中毒时血清IL-6的变化,以探讨IL-6在急性排斥反应的早期诊断、鉴别诊断中的意义。方法：采用双抗体夹心酶联免疫吸附法,对106例肾移植患者血清IL-6活性水平于肾移植手术前后进行动态监测。结果：肾移植术前,IL-6与对照组比较差别无显著性意义。术后第1天明显升高,2周左右基本降至术前水平。发生急性排斥反应前1-3天。血清IL-6即有升高,峰值出现在抗排斥反应治疗的当天,经甲基本降至术前水平,发生急性排斥反应前1-3天,血清IL-6即有升高,峰值出现在抗排斥反应治疗的当天,经甲基泼尼松尼（MP）冲击有效后迅速下降,治疗无效者,血清IL-6持续在高水平,并发感染时,IL-6也显著升高,与急性排斥反应组相比差别无显著性意义;而CsA中毒时,IL-6变化不明显。结论：动态监测IL-6可以作为急性排斥反应的早期诊断,鉴别诊断的免疫生物学指标。     

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.     

Increased serum beta 2 microglobulin during rejection, cyclosporine-induced nephrotoxicity, and cytomegalovirus infection in renal transplant recipients

In 83 renal transplant recipients, serum beta 2 microglobulin (beta 2m) levels were significantly elevated during pretransplant uremia, rejection, cyclosporine-induced nephrotoxicity, and infections. In patients with normal serum creatinine, 74% had elevated serum beta 2m levels. None of the cyclosporine-treated patients had normal levels of beta 2m. Patients with stable renal allograft function receiving cyclosporine showed significantly higher serum beta 2m (P less than 0.001) and serum creatinine (P less than 0.01) levels than azathioprine treated patients. Patients with an irreversible rejection showed significantly higher serum concentrations of beta 2m than patients experiencing a reversible rejection (P less than 0.001). During cytomegalovirus (CMV) infection the serum beta 2m levels were elevated compared with other infections (P less than 0.001), while the serum creatinine was not. However, infected patients had higher serum levels of beta 2m and creatinine than patients with stable renal allograft function (P less than 0.001). Serum beta 2m may therefore be useful in the early diagnosis of CMV infection. To conclude, serum beta 2m levels cannot distinguish between rejection, cyclosporine nephrotoxicity, or infection.     

Calcineurin inhibitor sparing in renal transplantation

Although calcineurin inhibitors (CNIs) are effective at preventing acute rejection, their long-term use is associated with nephrotoxicity that may compromise long-term renal allograft survival. Consequently, there is considerable interest in identifying immunosuppressive regimens that permit reduced exposure to CNIs while maintaining adequate immunosuppression. Introducing such strategies early after transplantation may mean that the development of CNI-associated nephrotoxicity could be minimized or prevented. Several CNI-sparing regimens have shown at least comparable efficacy with standard-dose CNI regimens. In particular, a regimen of mycophenolate mofetil (MMF), corticosteroids, interleukin-2 receptor antagonist induction, and low-dose tacrolimus from the time of transplantation provided superior renal function and a lower acute rejection rate than the same regimen but with low-dose cyclosporine or low-dose sirolimus, or standard-dose cyclosporine, MMF, and corticosteroids. The use of low-dose cyclosporine does not seem to eliminate nephrotoxicity in de novo renal transplant recipients. The early withdrawal of CNIs from MMF-based regimens generally improves renal function but has been associated with an increased risk of acute rejection, in particular when the levels of mycophenolic acid were not adjusted to maintain the same total level of immunosuppression. Research aiming to achieve the "best" balance of efficacy and toxicity of available immunosuppressive regimens continues.     

A randomized pilot study of cyclosporin G in renal transplantation

Animal studies have suggested that the analogue cyclosporin G (CyG) may be less nephrotoxic than cyclosporin A (CyA). A pilot study was therefore performed in 10 primary cadaveric renal allograft recipients who were randomized to receive posttransplant immuno-suppression with either CyA or CyG. The follow-up time was a minimum of 1 year. One graft was lost in each group. All patients in both groups experienced at least one acute rejection episode. Episodes of acute nephrotoxicity were observed in both groups. Renal function, as assessed by determinations of the serum creatinine level and chromium-ethylene diamine tetra-acetic acid (Cr-EDTA) clearance, did not differ between the two groups. Renal allograft biopsies showed a significantly higher degree of fibrosis in the CyG group than in the CyA group. All CyG-treated patients evidenced laboratory signs of acute liver toxicity, which was dose-dependent and reversible. Today, all CyG-treated patients have been switched to CyA. This study shows that immunosuppression after renal transplantation in man is possible with CyG; however, it does not seem to have any advantages over CyA.