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1.
Mycophenolate mofetil (MMF) is increasingly used to prevent acute and chronic rejection following kidney transplantation and in autoimmune diseases. Here, we report on a patient after kidney transplantation, who developed an acute inflammatory syndrome characterized by fever and oligoarthritis within 1 week after increasing the MMF dosage. MMF was discontinued resulting in a complete resolution of the syndrome within 48 h. We demonstrated in vitro that the patient's phorbol myristate acetate (PMA-) and formyl Met-Leu-Phe (fMLP-) stimulated polymorphonuclear neutrophils (PMNs) developed increased oxidative burst when incubated with MMF. This report demonstrates that MMF can also induce acute inflammatory syndrome in patients following kidney transplantation and that this syndrome might be due to a paradox, pro-inflammatory reaction of PMNs.  相似文献   

2.
The advent of novel immunosuppressive strategies in renal transplantation, with immunomodulatory properties, might facilitate long‐term allograft survival. T‐cell depletion, costimulation‐blockade and mTor inhibition have been shown to favour anti‐donor hyporesponsiveness. Recently, the combination of rATG, belatacept (Bela) and sirolimus (SRL) has been used in kidney transplantation, showing very low incidence of acute rejection and excellent 12‐month graft and patient survival. Herein, we have analysed the 1‐year evolution of memory/effector and regulatory T cells and assessed the donor‐specific T‐cell alloimmune response in a group of these patients and compared with others treated with a calcineurin‐inhibitor(CNI)‐based (rATG/tacrolimus/MMF), and two other Bela‐based regimens (rATG/Bela/MMF and basiliximab/Bela/MMF/steroids). During the first year after transplantation, patients receiving rATG/Bela/SRL had significantly higher percentage of Tregs upon the memory T‐cell compartment and showed a potent anti‐donor suppressive activity. In an in vitro naive and memory/effector T‐cell co‐culture, the combination of costimulation‐blockade and SRL could abrogate both antigen‐specific T‐cell responses as efficiently as using a CNI drug. The combination of T‐cell depletion, costimulation‐blockade and mTor inhibition seems to be able to allow Treg survival and inhibit donor‐specific alloreactive effector immune responses after kidney transplantation in humans.  相似文献   

3.
The authors report the case of a newborn male with an exceptional type of anorectal atresia with a fistula that passes posterior to the muscle complex and exits at a site just to the tip of the coccyx. This anorectal malformation was associated with other abnormalities including agenesis of the right kidney, pyelic dilatation of the left kidney, duplicity, and left megaureter. There was no defect in the spine. The anorectal malformation was managed successfully by a posterior sagittal approach according to the Pena procedure.  相似文献   

4.
Mycophenolate mofetil (MMF) has been used successfully as an immunosuppressive agent after kidney and heart transplantation, but experience with MMF after liver transplantation is still limited. Between August 1995 and January 1996, we treated 20 patients with MMF after orthotopic liver transplantation in an open, prospective study. Five out of eight patients with acute rejection and one patient with early chronic rejection showed a complete response after MMF was added to the immunosuppression. Three patients with chronic rejection did not improve, one died, and two have stable graft function at present. In eight patients who suffered from toxicity, a reduction in the dosage of tacrolimus was attempted with simultaneous MMF therapy. One patient died due to multiple organ failure. Liver function improved completely in one other patient, and partially in three patients after adding MMF. In the remaining three patients, a reduced dosage of tacrolimus or cyclosporin, together with MMF, reduced toxicity, not significantly. In conclusion, MMF appears to be a safe and potentially useful adjuvant immunosuppressive agent for rescue and maintenance therapy. Received: 15 August 1996 Accepted: 6 December 1996  相似文献   

5.
Mycophenolate mofetil (MMF) is a potent immunosuppressive agent used to prevent acute and chronic rejection in kidney transplantation or for rescue therapy. One side effect of MMF is bone marrow toxicity, including leukopenia, which may necessitate drug withdrawal. We report 2 patients who underwent kidney transplantation and developed leukopenia while receiving MMF and safely switched to sirolimus. A 35-year-old woman underwent deceased donor kidney transplantation. She received basiliximab, tacrolimus, MMF, and a corticosteroid. On postoperative day (POD) 75, her white blood cell (WBC) count was 1800/μL. A 44-year-old women underwent deceased donor kidney transplantation and received basiliximab, tacrolimus, MMF, valganciclovir, and a corticosteroid. On POD 88, her WBC count was 1320/μL. MMF was switched to sirolimus, resulting in recovery of WBC count without rejection. Switch from MMF to sirolimus is safe and favorable in MMF-induced leukopenia in renal transplant recipient.  相似文献   

6.
BK virus infection in kidney transplant recipients   总被引:7,自引:0,他引:7  
INTRODUCTION: Nephropathy associated with the polyomavirus type BK virus (BKV) has emerged as a cause of allograft failure linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil (MMF). The outcome in BKV nephropathy is generally unfavorable, namely 50% of patients lose graft function. We herein report nine cases of BKV nephropathy after kidney transplantation. METHODS: From October 1998 to May 2003, 138 of 169 consecutive kidney transplant patients received tacrolimus-based immunosuppression, and 31 received cyclosporine-based immunosuppression. Additionally, 88.2% of the patients received mycophenolate mofetil (MMF). The diagnosis of BK infection was made by the presence of decoy cells in the urine and by allograft biopsy. RESULTS: There were nine cases of BKV nephropathy in kidney transplant recipients, an incidence of 5.3%. All patients with BKV nephropathy received tacrolimus, MMF, and steroids. The median time to diagnosis of BKV infection was 7.8 months after transplantation. All patients experienced an elevated serum creatinine, which stabilized or decreased in seven patients with altered or decreased immunosuppression. After a mean follow-up of 11.1 months, 2 (22.2%) of nine patients lost the graft. CONCLUSION: Because BKV nephropathy is a rare but serious complication after kidney transplantation, it should be included in the clinical differential of transplant dysfunction. In the absence of documented antiviral treatment, early diagnosis and judicious use of immunosuppressive agents is indicated to minimize the occurrence of BKV infection.  相似文献   

7.
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.  相似文献   

8.
Cytomegalovirus (CMV) disease typically occurs 1 to 4 months (median 35 days) after solid organ transplantation. Recent reports documented that the natural history of CMV disease associated with solid organ transplantation has been modified as a result of the widespread use of potent immunosuppressents and antiviral prophylaxis. We herein report three pretransplant CMV seropositive recipients (with unknown donor status) who were diagnosed recently to display late and atypical CMV disease. Two men and one woman included two patients who presented with allograft dysfunction at 12 years and at 3 years after transplantation. Both patients showed increased serum creatinine approximately from baseline 200 to >400 micromol/L over 3 months in the absence of features of rejection or cyclosporine toxicity. A renal biopsy was refused by both patients. Two of the three patients presented with symptoms of enterocolitis (diarrhea, nausea, weight loss), which had persisted for more than 6 months. Other symptoms and signs of overt CMV disease (fever, leukopenia) were absent. None had pulmonary, hepatic, or other major organ involvement. In all patients IgG antibodies and CMV DNA by polymerase chain reaction were positive with negative IgM antibodies. The immunosuppressive regimen consisted of mycophenolate mofetil (MMF), steroids, and calcineurin inhibitors. The kidney function significantly improved in both patients with renal dysfunction. Gastrointestinal symptoms resolved completely with gradual weight gain. The recognition and early diagnosis of late atypical CMV disease in kidney transplant patients presenting with allograft dysfunction and/or other organ systems is important. The MMF has a red herring effect in our cases due to its GI side effects.  相似文献   

9.
Fu YF  Liu GL 《Clinical nephrology》2001,55(4):318-321
We describe mycophenolate mofetil (MMF), a new immunosuppressive agent, to be a therapy of two children with lupus nephritis which were refractory to both cyclophosphamide (CyP) and cyclosporine (CsA). After 11- to 12-month course of MMF treatment, all clinical symptoms of lupus disappeared and serum antibodies became negative. MMF might be a promising curative for cyclophosphamide-resistant lupus nephritis in children. Cyclophosphamide intravenous bolus therapy is generally considered to be the treatment for patients with lupus nephritis. However, there is little guidance about what to do if such therapy fails. Recently, a new immunosuppressive agent, mycophenolate mofetil (MMF), has been used to treat cyclophosphamide-resistant lupus nephritis [Dooley et al. 1999, Gaubitz et al. 1999, Glicklich and Acharga 1998] in adults and has been recognized as a promising curative for lupus nephritis. Up to now, MMF has been adopted widely with solid organ transplantation to prevent or reverse acute rejection [Mathew 1998, Morris-Stiff and Jurewicz 1998] and has been used successfully to treat for rheumatoid arthritis refractory to a variety of other drugs. But there is no report about MMF treatment in children with cyclophosphamide-resistant lupus nephritis. We describe our experience with MMF treatment in two Chinese children with lupus nephritis that were refractory not only to cyclophosphamide but also to cyclosporine.  相似文献   

10.
Mycophenolate mofetil (MMF) is a safe and effective immunosuppressive agent in kidney and liver transplantation. Preliminary studies also support its use in heart transplantation. However, the cost of MMF is substantially greater than azathioprine (AZA), the current alternative. Since the majority of rejection episodes occur within the first few months of transplantation, using MMF early after transplantation and subsequently converting to AZA, after the risk of rejection has diminished, might be cost-effective. In order to evaluate the safety of such a strategy in heart transplant recipients, we reviewed the rejection profiles of a group of patients who were converted from MMF to AZA late after transplantation. Forty-three stable patients on chronic MMF therapy as part of an open-label, long-term safety study were converted to either commercially available MMF (CellCept) or AZA, at the conclusion of the study. Demographic variables, rejection histories before and after conversion, and immunosuppressive regimens were examined. Twenty-three patients were continued on commercial MMF and 20 were converted to AZA therapy. The average duration of MMF therapy prior to conversion was 41 months in each group. Baseline demographics were similar in the two groups. Treated allograft rejection occurred in 10 of 20 patients converting to AZA, as compared to only 1 of 23 patients remaining on MMF; p = 0.002. Additionally, mean scores (1-5 scale) for the three biopsies before and after conversion favored continued MMF therapy (1.5+/-0.6 before and 1.2+/-0.4 after conversion in MMF group vs. 1.3+/-0.5 before and 1.7+/-0.9 after conversion to AZA; p = 0.02). No allograft loss occurred as a result of conversion. These data suggest that conversion from MMF to AZA, even late after transplantation, can be associated with allograft rejection. The costs associated with these rejection episodes (the additional immunosuppressive agents, endomyocardial biopsies, and physician visits) may exceed the potential cost savings of converting stable heart transplant recipients from MMF to AZA.  相似文献   

11.
Mycophenolate mofetil (MMF) is an immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T and B lymphocytes. Standard primary immunosuppressive therapy after orthotopic liver transplantation (OLT) is based on a calcineurin-inhibitor (CNI): cyclosporine or tacrolimus. Renal failure with arterial hypertension, due to CNI side-effects, is a major cause of morbidity and mortality after OLT. Several studies have shown the efficacy of MMF to improve CNI-induced nephrotoxicity, blood pressure, and uric acid concentration in liver transplant patients with concomitant reduction or withdrawal of CNI. Predose plasma mycophenolic acid concentrations (MPA) are related to adverse events, drug dose, and clinical status. Blood level values outside the suggested MPA therapeutic range are associated with acute rejection episodes and side effects, which have been described in about half of the patients treated with MMF. Most authors have described gastrointestinal and hematological side-effects, whereas these appear usually dose related, responding quickly to reduction. MMF is potent and safe immunosuppressive agent, and replacement of CNI by MMF in liver transplant patients with renal dysfunction may improve not only kidney function but also other CNI-associated side-effects, such as hypertension and hyperuricemia, with a low risk of rejection.  相似文献   

12.
Sun Q  Tang Z  Chen J  Chen H  Liu Z  Li L 《Transplantation proceedings》2005,37(10):4244-4245
In renal transplantation, C4d-positive acute humoral rejection (AHR) usually develops in the early stage posttransplantation. It is clear C4d can be detected late after the operation, when it is associated with chronic renal allograft rejection. We report a case of a renal allograft recipient who experienced C4d-positive acute renal allograft rejection associated with withdrawal of mycophenolate mofetil (MMF) at 10 months after transplantation. This 21-year-old single male patient received his first cadaveric renal allograft under immunosuppression with cyclosporine, MMF, and prednisolone. The serum creatinine recovered to the normal range within 4 days. A protocol biopsy performed at 1 month after transplantation revealed no signs of rejection. The graft function was stable until 10 months postoperation, when MMF was converted to mizoribin. Three days later a biopsy showed a C4d-positive rejection. Patient had no response to the MMF combined with tacrolimus and steroid bolus therapy, which generally improves 85% of AHR among Chinese. He finally returned to dialysis. Our report suggested that C4d positive AHR may occur late after transplantation. MMF is important to suppress the body's humoral response to allograft; when MMF was converted to a weaker immunosuppressant, the dose of the other immunosuppressants (cyclosporine for example) must be adjusted properly.  相似文献   

13.
Patient and graft survival following renal transplantation have improved markedly over the past decade, meaning that physician attention has turned more towards minimizing short- and long-term toxicities associated with immunosuppressive regimens. Gastrointestinal (GI) adverse events are common following renal transplantation and all immunosuppressive regimens have been associated with such events. Mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) are potential components of immunosuppression regimens, and are associated with the most successful outcomes in kidney transplantation. The effects of MMF and EC-MPS are likely mediated via the active metabolite mycophenolic acid (MPA). The GI events caused by both MMF and EC-MPS may, in part, be related to MPA, independent of the formulation or route of administration. MPA may produce GI events either through direct action or through the action of it metabolites. However, many other factors may cause GI events observed following renal transplantation. These include the surgery itself and concurrent diseases such as diabetes, and bacterial, viral, fungal and parasitical infections. Additionally, numerous concomitant non-immunosuppressive agents, including antibiotics hypoglycaemic and proton-pump inhibitors, can be associated with GI events. In a recent trial in renal transplant patients with severe diarrhoea, approximately 50% of patients achieved resolution of diarrhoea through methods other than altering their immunosuppressive regimens. Indeed altering of the immunosuppressive regimen may lead to the risk of acute rejection. Thus, in order to reduce the risk of rejection and subsequent damage to the graft, it is important to consider other causes of GI events in renal transplant patients before altering immunosuppressive regimens.  相似文献   

14.
BACKGROUND: Tapering of immunosuppressive medication is indicated to prevent long-term side effects. Recently, we have shown that renal transplant recipients can safely be converted from calcineurin inhibitors to MMF or AZA when their donor-specific cytotoxic T-lymphocyte precursor frequencies (CTLpf) are below 10/10(6) PBMC. We wondered whether a low CTLpf also had predictive value when immunosuppressive medication was reduced in patients only on MMF or AZA and steroid medication. METHODS: Renal transplant recipients with stable renal function at least 2 years after transplantation and with low (<10/10(6) PBMC) CTLpf were included. Their MMF or AZA dose was reduced to 75% and to 50% of the original dose at 4 months and 8 months after inclusion. Endpoint of the study was 12 months after inclusion or developing acute rejection. RESULTS: Forty-five patients have reached the 1-year follow up endpoint. Their median time after transplantation was 4.2 years (range 2.0-15.5 years). Acute rejection was seen in one patient only (who had discontinued all his medication). CONCLUSION: In patients with low CTLpf long after kidney transplantation, a 50% reduction of immunosuppression is safe and further decreasing their immunosuppressive load is the obvious next step.  相似文献   

15.
BACKGROUND: Recipients of simultaneous kidney-pancreas transplantation receive a combination of polyclonal antithymocyte globulin (ATG), cyclosporin or tacrolimus, mycophenolate mofetil (MMF) and corticosteroids (Cs). To avoid the side effects and adverse events associated with Cs, we investigated a new immunosuppressive regimen without Cs after simultaneous kidney-pancreas transplantation. METHODS: A total of 28 consecutive patients who underwent simultaneous kidney-pancreas transplantation were included in this study. All patients received ATG, cyclosporin, and MMF. RESULTS: All patients but one tolerated the ATG course well. MMF was definitively discontinued in three patients because of leukopenia. Cytomegalovirus infection was diagnosed in eight patients (28.5%). Only two patients (7%) required an antirejection treatment. Patient, kidney, and pancreas survival is currently 96.4, 96.4, and 75%, respectively. CONCLUSIONS: The combination of ATG, cyclosporin, and MMF, without Cs, was well tolerated. The unexpectedly low (7%) incidence of acute kidney rejection observed suggests that Cs may partially interfere with the immunosuppressive effect of ATG.  相似文献   

16.
BACKGROUND: Mycophenolate mofetil (MMF) has been shown to decrease acute rejection episodes after kidney transplantation, and has been associated with better graft and patient survival vs azathioprine (AZA). Previous studies reported a higher risk of death due to infection in elderly recipients treated with MMF-based immunosuppression. METHODS: We analysed 5069 elderly ( > 65 years of age) primary renal allograft recipients treated with either MMF or AZA reported to the Scientific Registry of Transplant Recipients between 1988 and 2000, and compared rates of acute rejection, late acute rejection, graft survival, death-censored graft survival, patient survival and death with a functioning graft. RESULTS: In Cox proportional hazard models, MMF was associated with lower rates of late acute rejection with 12 (RR = 0.72, P = 0.11) and 24 months (RR = 0.50, P = 0.028) of continuous therapy. In univariate analysis (Kaplan-Meier), MMF was associated with improved patient (P = 0.0003) and graft (P<0.0001) survival vs AZA, and trends toward improved patient and graft survival in multivariate analyses. CONCLUSIONS: These findings demonstrate the efficacy of MMF-based immunosuppression in elderly transplant recipients and do not suggest an increased risk of death compared to treatment with AZA.  相似文献   

17.
BACKGROUND: Aiming at reducing cyclosporine toxicity, we investigated safety and efficacy of mycophenolate mofetil (MMF) as an immunosuppressive drug in pediatric kidney transplantation compared with cyclosporine (CsA), both in combination with corticosteroids. METHODS: One year after kidney transplantation, children on triple immunosuppression, having experienced no more than one, steroid-sensitive, acute rejection episode, were randomized to withdrawal of either CsA or MMF and were followed for 2 yr. RESULTS: In each group, two patients had an acute rejection episode during withdrawal. Treatment failure occurred in 3 of 21 MMF and 5 of 23 CsA patients. Final analysis was for 18 patients in either group. A larger than 10 mL/min 1.73 m decrease in glomerular filtration rate was observed in more patients on CsA than on MMF (73% vs. 29%, P=0.019). No differences in blood pressure or nightly decrease of blood pressure were noted. Hypercholesterolism improved in the MMF (-16%), but not the CsA group (+5%, P<0.05), over the first, but not over both study years. Differences in triglycerid levels between groups were not shown. At study end, MMF patients tended to have lower hemoglobin levels than patients on CsA. Two MMF patients experienced a first acute rejection episode during the second study year, resulting in chronic transplant glomerulopathy with graft loss in one and deterioration of kidney function in the other. CONCLUSION: In pediatric kidney transplantation, maintenance immunosuppression with MMF together with corticosteroids has short-term benefits for kidney function and lipid pattern compared with CsA but is not without risk of complications.  相似文献   

18.
目的 探讨下尿路异常患者的肾移植手术治疗方案及方法。 方法  3例合并下尿路异常的肾移植患者均为男性。结核性膀胱挛缩 1例 ,4 5岁 ,行肾移植加移植肾输尿管皮肤造口术 ,免疫抑制方案为赛尼哌 (Zenapax) 他克莫司 (FK5 0 6 ) 霉酚酸酯 (MMF) 泼尼松 (Pred) ;神经原性膀胱2例 :例 1 ,2 4岁 ,同期行肾移植加回肠膀胱术 ,免疫抑制方案为Zenapax FK5 0 6 MMF Pred。例 2 ,34岁 ,分期行肾移植加回肠膀胱术 ,免疫抑制方案为Zenapax CsA MMF Pred。 结果 行移植肾输尿管皮肤造口术者术后恢复顺利。同期行肾移植加回肠膀胱术患者术后血便和尿瘘 ,积极治疗后好转 ;分期手术者无明显并发症。术后分别随访 2 3、5、4个月 ,移植肾功能正常 ,无严重并发症。 结论 合并下尿路异常的肾移植患者 ,应根据患者情况分期或同期完成肾移植术和尿流改道术 ,最大限度保障移植肾功能与输尿管引流通畅  相似文献   

19.
Steroid-induced adverse effects after transplantation include cosmetic, metabolic, and cardiovascular complications. Steroid withdrawal or avoidance with cyclosporine-based regimens have been hampered by an unacceptably high rate of acute rejections and increased rates of graft loss. Recently the results of several large, randomized trials of steroid withdrawal/avoidance with tacrolimus-based immunosuppression in renal transplant recipients became available. A review of these trials appeared to be of clinical interest. Data from the THOMAS trial clearly indicate that steroid withdrawal from a regimen of tacrolimus, mycophenolate mofetil (MMF), steroids after 3 months after transplantation is safe with regard to acute rejection rate and graft survival. If an induction therapy with daclizumab is used in combination with tacrolimus and MMF (CARMEN trial), even steroid avoidance is safe with regard to acute rejection rate and graft survival. Finally, in the ATLAS trial, steroid avoidance with basiliximab in combination with tacrolimus (resulting in tacrolimus monotherapy) or alternatively with tacrolimus and MMF both resulted in similar graft survival, but higher rates of acute rejection. In conclusion, steroid withdrawal is safe from a triple-drug regimen of tacrolimus, MMF, and steroids after 3 months after transplantation, and steroid use may completely be avoided with tacrolimus, and MMF combined with daclizumab induction. Tacrolimus monotherapy may be achieved using basiliximab induction at the price of higher rates of acute rejection, but with unaffected graft survival. Thus tacrolimus-based immunosuppression with or without interleukin-2 receptor antagonist induction has made steroid withdrawal or avoidance a realistic option in renal transplantation.  相似文献   

20.
The aim of this study was to assess the effects of 1 g of mycophenolate mofetil (MMF) on T-cell function and inosine monophosphate dehydrogenase (IMPDH) activity among patients undergoing kidney transplantation. Five patients undergoing renal transplantation from a living donor were enrolled in this study. Compared to baseline (before MMF intake), CD25 and CD71 expression were significantly decreased during the first hour following MMF intake. T-cell proliferation and IMPDH activity also decreased dramatically. Thereafter, all biomarker levels increased over time. At 4 hours, CD25 and CD71 levels, as well as IMPDH activity, returned to almost baseline values, whereas T-cell proliferation remained below baseline. Intracytoplasmic IL-2 expression remained unchanged after MMF ingestions. In conclusion, administration of 1 g of MMF was associated with a transient decrease in CD25 expression in addition to a temporary dramatic decrease in both T-cell proliferation and IMPDH activity.  相似文献   

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