Current use of immunosuppressive agents in inflammatory bowel disease patients in East China

AIM:To investigate immunosuppressive agents used to treat inflammatory bowel disease(IBD)in East China. METHODS:A retrospective review was conducted, involving 227 patients with IBD admitted to Sir Run Run Shaw Hospital,College of Medicine,Zhejiang University from June 2000 to December 2007.Data regarding demographic,clinical characteristics and immunosuppressants usage were analyzed. RESULTS:A total of 227 eligible patients were evaluated in this study,including 104 patients with Crohn’s disease and 123 with ulcerative colitis.Among the patients,61 had indications for immunosuppressive agents use.However,only 21 (34.4%)received immunosuppressive agents.Among the 21 patients,6(37.5%)received a subtherapeutic dose of azathioprine with no attempt to increase the dosage.Of the 20 patients that received immunosuppressive agent treatment longer than 6 mo,15 patients went into remission,four patients were not affected and one relapsed.Among these 20 patients,four patients suffered from myelotoxicity and one suffered from hepatotoxicity.CONCLUSION:Immunosuppressive agents are used less frequently to treat IBD patients from East China compared with Western countries.Monitoring immunosuppressive agent use is recommended to optimize dispensation of drugs for IBD in China.

Systematic Review and Meta-analysis:Immunosuppressive Agents for the Treatment of Primary Biliary Cholangitis

Background and aim:There are still no clinically satisfactory therapy for PBC.This study was performed to assess the safety and efficacy of IAs for the therapy of PBC.Methods:Relevant studies were identified and selected by searching PubMed,Web of Science and Cochrane Library databases.The primary outcome was defined as the need for mortality or liver transplantation.Adverse effects and liver biochemical variables were a secondary outcome.Results:Nine randomized controlled trials,involving six different treatment regimens with a total of 996 patients,were included in the analysis.On meta-analysis,IAs was not associated with a reduction in risk of mortality or liver transplantation(risk ratio[RR]:0.92,95% confidence interval[CI]:0.69-1.22,P=0.57,P=0%),and have resulted in more adverse effects(RR:1.44,95%CI:1.08-1.92,P=0.01,P=19%).Subgroup analysis showed that IAs monotherapy caused adverse effects such as diarrthea,abdominal pain,and renal insufficiency(RR:1.36,95% CI:1.01-1.82,P=0.04,P=48%).IAs therapy did not prominently improve markers of liver function except for alkaline phosphatases(weighted mean difference[WMD]:-0.38,95% CI:-0.62 to-0.14,P=0.002).Conclusions:IAs cannot reduce the risk of mortality or liver transplantation,whether in IAs monotherapy or combination therapy,and even be associated with more adverse effects.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients

BACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019(COVID-19)but its full correlation with COVID-19 infection remains unknown.AIM To identify acute pancreatitis’occurrence,clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19.METHODS A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19.Data were obtained from hospital electronic medical records.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab.RESULTS Four hundred and eight out of 1432(28.49%)patients who received a renal allograft developed COVID-19 disease.The analyzed cohort included 321 patients(57%males).One hundred and fifty patients(46.7%)received at least one dose of the anti-SARS-CoV-2 vaccine before the infection.One hundred twenty-five(39.1%)patients required hospitalization,141(44.1%)developed pneumonia and four patients(1.3%)required mechanical ventilation.Treatment included immunosuppression modification in 233 patients(77.1%)and remdesivir in 53 patients(16.6%),besides the other supportive measures.In the study cohort,only one transplant recipient(0.3%)developed acute pancreatitis during acute COVID-19,presenting with abdominal pain and significantly elevated pancreatic enzymes.She survived without complications with a stable kidney allograft function.CONCLUSION Although rare,acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients.The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

Hepatitis C virus reinfection after liver transplantation: Is there a role for direct antiviral agents?

Recurrence of hepatitis C virus(HCV)infection following liver transplantation(LT)is almost universal and can accelerate graft cirrhosis in up to 30%of patients.The development of effective strategies to treat or prevent HCV recurrence after LT remains a major challenge,considering the shortage of donor organs and the accelerated progression of HCV in LT recipients.Standard antiviral therapy with pegylated-interferon plus ribavirin is the current treatment of choice for HCV LT recipients,even though the combination is not as effective as it is in immunocompetent patients.A sustained virological response in the setting of LT improves patient and graft survival,but this is only achieved in 30%-45%of patients and the treatment is poorly tolerated.To improve the efficacy of pre-and post-transplant antiviral therapy,a new class of potent direct-acting antiviral agents (DAAs)has been developed.The aim of this review is to summarize the use of DAAs in LT HCV patients.PubMed,Cochrane Library,MEDLINE,EMBASE,Web of Science and clinical trial databases were searched for this purpose.To date,only three clinical studies on the topic have been published and most of the available data are in abstract form.Although a moderately successful early virological response has been reported,DAA treatment regimens were associated with severe toxicity mitigating their potential usefulness.Moreover,the ongoing nature of data,the lack of randomized studies,the small number of enrolled patients and the heterogeneity of these studies make the results largely anecdotal and questionable.In conclusion,large welldesigned clinical studies on DAAs in HCV LT patients are required before these drugs can be recommended after transplantation.

Protective effect of glucocorticoid-free immunosuppressive regimen in allogenic islet transplantation

BACKGROUND: The most common complication after allogenic islet transplantation is rejection. This study was to evaluate the effect of anti-rejection of glucocorticoid-free immunosuppressive regimen on allogenic islet transplantation. METHODS: Tacrolimus(FK506)+mycophenolate mofetil (MMF) and FK506+MMF+prednisone (Pred) were administered respectively for 2 weeks to inhibit rejection after allogenic islet transplantation in rats, which were compared with the control group. The concentrations of blood glucose, insulin and C-peptide were determined dynamically in recipients and the sites of transplantation were observed morphologically. RESULTS: As compared with the control group without immunosuppressive agents, FK506+MMF and FK506+MMF+Pred could prolong the survival time of grafts significantly. There were many morphologically intact islets in the liver of recipients 2 months after transplantation. Group FK506+MMF kept normal levels of blood glucose, insulin and C-peptide beyond 60 days after transplantation. In contrast, group FK506+MMF+Pred secreted less C-peptide(P<0.05) and maintained a higher level of blood glucose concentration (P<0.01) after the operation. There was no significant difference in insulin concentrations between the two groups. The level of blood glucose beyond the first 2 weeks after drug withdrawal in group FK506+MMF+Pred decreased obviously (P<0.05), and the secretion of insulin and C-peptide increased. These results were compared with those the first 2 weeks after transplantation and the first 2 weeks after drug withdrawal. CONCLUSIONS: Both regimens of FK506+MMF and FK506+MMF+Pred could provide effective immunosup-pression. Moreover the combined glucocorticoid-free immunosuppressive strategy of low-dose FK506 and MMF could protect islet grafts in islet transplantation without diabetogenic side-effects.

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’T cell ferroptosis

BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.

Integrated Chinese and Western medicine in the treatment of a patient with podocyte infolding glomerulopathy:A case report

BACKGROUND Podocyte infolding glomerulopathy(PIG)is a newly described and rare glomerular disease.To date,only approximately 40 cases have been reported globally.CASE SUMMARY A 26-year-old female patient presented to our hospital with a complaint of intermittent edema of both lower limbs over the past 2 years.The patient was diagnosed with PIG.She was prescribed corticosteroid therapy in other hospitals during the initial stage,to which she had responded poorly and had developed femoral head necrosis.Therefore,we administered immunosuppressants,reninangiotensin system inhibitors,combined with traditional Chinese medicine.The patient was followed for 1 year,during which her clinical condition improved.CONCLUSION Integrated Chinese and Western medicine may be effective for PIG treatment,which requires active intervention to improve prognosis.

Overlap syndromes among autoimmune liver diseases

The three major immune disorders of the liver are autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC) and primary sclerosing cholangitis(PSC).Variant forms of these diseases are generally called overlap syndromes,although there has been no standardised definition.Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC.The AIH-PBC overlap syndrome is the most common form,affecting almost 10% of adults with AIH or PBC.Single cases of AIH and autoimmune cholangitis(AMA-negative PBC) overlap syndrome have also been reported.The AIH-PSC overlap syndrome is predominantly found in children,adolescents and young adults with AIH or PSC.Interestingly,transitions from one autoimmune to another have also been reported in a minority of patients,especially transitions from PBC to AIH-PBC overlap syndrome.Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment.Therapy for overlap syndromes is empiric,since controlled trials are not available in these rare disorders.Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes.In end-stage disease,liver transplantation is the treatment of choice.

Protective effects of cyclosporine A on T-cell dependent ConA-induced liver injury in Kunming mice

INTRODUCTIONThe T-cell dependent specific liver injury in mice induced by concanavalin A(ConA) is a newly cstablished experimental liver injury model,which is considered more eligible for the study on pathophysiology of several human liver discascs,such as viral hepatitis and autommune hepatitis[1-9].T cell activation and several cytokines release had been proven to play a critical role in ConA -induced liver injury[10-19].Cyclosprine A(CsA),an effective inhibitor of activation of T lymphocytc,hes been used widely in clinical treatment,especially in autoimmune diseases and organ transplantation[20-25].In this study,we investigated the possible effect of CsA on ConA-induced liver injury in Kunning mice.

Expert consensus on management of metabolic disease in Chinese liver transplant recipients

Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and death.The development of metabolic disease is closely related to the side effects of immunosuppressants.Therefore,optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic disease.The Chinese Society of Organ Transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent studies.Emphasis is placed on the risk factors of metabolic diseases,the effect of immunosuppressants on metabolic disease,and the prevention and treatment of metabolic diseases.

Impact of non-oncological factors on tumor recurrence after liver transplantation in hepatocellular carcinoma patients

Hepatocellular carcinoma (HCC) is the most common primary neoplasm of the liver and is one of the leading causes of cancer-related death worldwide. Liver transplantation (LT) has become one of the best curative therapeutic options for patients with HCC, although tumor recurrence after LT is a major and unaddressed cause of mortality. Furthermore, the factors that are associated with recurrence are not fully understood, and most previous studies have focused on the biological properties of HCC, such as the number and size of the HCC nodules, the degree of differentiation, the presence of hepatic vascular invasion, elevated serum levels of alpha-fetoprotein, and the tumor stage outside of the Milan criteria. Thus, little attention has been given to factors that are not directly related to HCC (i.e., &#x0201c;non-oncological factors&#x0201d;), which have emerged as predictors of tumor recurrence. This review was performed to assess the effects of non-oncological factors on tumor recurrence after LT. The identification of these factors may provide new research directions and clinical strategies for the prophylaxis and surveillance of tumor recurrence after LT, which can help reduce recurrence and improve patient survival.

Initial steroid-free immunosuppression after liver transplantation in recipients with hepatitis c virus related cirrhosis

AIM:Steroids can increase hepatitis C virus(HCV) replication.After liver transplantation(LTx),steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid dosages.Steroids can worsen the outcome of recurrent HCV infection.Therefore, we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free immunosuppression. METHODS:Thirty patients undergoing LTx received initial steroid-free immunosuppression.Indication for LTx included 7 patients with HCV related cirrhosis.Initial immunosuppression consisted of tacrolimus 2×0.05mg/kg.d po and mycophenolate mofetil(MMF)2×15mg/kg.d po.The tacrolimus dosage was adjusted to trough levels in the target range of 10-15μg/L during the first 3 mo and 5-10μg/L thereafter.Manifestations of acute rejection were verified histologically. RESULTS:Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 years.Acute rejection occurred in 8/30 patients, including 1 HCV infected recipient.All HCV-infected patients had HCV genotype Ⅱ(lb).HCV seropositivity occurred within the first 4 mo after LTx.The virus load was not remarkably increased during the first year after LTx.Histologically,grafts had no severe recurrent hepatitis. CONCLUSION:From our experience,initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver recipients.Furthermore,none of the HCV infected patients developed serious chronic liver diseases.It suggests that it may be beneficial to avoid steroids in this particular group of patients after LTx.

Conversion of twice-daily to once-daily tacrolimus is safe in stable adult living donor liver transplant recipients

Once-daily extended-release tacrolimus （Tac-OD） has been introduced as a useful therapeutic option to increase patient adherence to immunosuppressive therapy. This study aimed to evaluate the safety, efficacy and immunosuppressant adherence of conversion from twice-daily tacrolimus （Tac-BID） to Tac-OD in stable adult living donor liver transplant （LDLT） recipients in a single institution. METHODS： Between February and May 2013, Tac-BID was converted to Tac-OD in recipients followed up for at least 12 months after transplantation and without previous rejection episodes. The switching policy was based on a dose ratio of 1：1 with dose adjustment target trough levels at 3-5 ng/mL. Tacro- limus trough levels, laboratory parameters, metabolic disor- ders, and adverse events were assessed. RESULTS： A total of 229 patients were enrolled in the study. The median age at conversion was 53 years （range 31-73）. The median transplant duration was 35.3 months （range 12.0-95.4）. During a median follow-up of 13.5 months after conversion, 9 patients returned to Tac-BID because of adverse events. No acute rejection episodes were observed. Of 214 patients still on Tac-OD at 12 months, 12 （5.6%） received a reduced dose and 95 （44.4%） required an increased dose over baseline. Overall adherence was 82.2% at the end of follow-up. CONCLUSION： The conversion from Tac-BID to Tac-OD with similar target trough levels after conversion is safe and effec- tive for long-term stable LDLT patients.

Fertility and pregnancy in inflammatory bowel disease

INTRODUCTIONInflammatory bowel disease(IBD)is a chronic disorder affecting young adults in the reproductive years.It is comon for both female and male patients with IBD to ask questions about IBD's effect on their relationships,sexual and reproductive function,in particular fertility,the outcome of pregnancy and its possible effets on the disease.An open discussion of the social situation and education targeted at these issues therefore forms an essential part of the management of any young person with IBD.the questions that are most commonly asked are summarised in Table 1.In order to answer these questions we need evidence.There are few large prospective case controlled studies to provide the information which is required but the available data,some of it from small observational studies,will be summarised in this chapter.

Microscopic colitis

Microscopic colitis may be defined as a clinical syndrome, of unknown etiology, consisting of chronic watery diarrhea, with no alterations in the large bowel at the endoscopic and radiologic evaluation. Therefore, a definitive diagnosis is only possible by histological analysis. The epidemiological impact of this disease has become increasingly clear in the last years, with most data coming from Western countries. Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management. Collagenous colitis is characterized by a thickening of the subepithelial collagen layer that is absent in LC. The main feature of LC is an increase of the density of intra-epithelial lymphocytes in the surface epithelium. A number of pathogenetic theories have been proposed over the years, involving the role of luminal agents, autoimmunity, eosinophils, genetics (human leukocyte antigen), biliary acids, infections, alterations of pericryptal fibroblasts, and drug intake; drugs like ticlopidine, carbamazepine or ranitidine are especially associated with the development of LC, while CC is more frequently linked to cimetidine, non-steroidal antiinflammatory drugs and lansoprazole. Microscopic colitis typically presents as chronic or intermittent watery diarrhea, that may be accompanied by symptoms such as abdominal pain, weight loss and incontinence. Recent evidence has added new pharmacological options for the treatment of microscopic colitis:the role of steroidal therapy, especially oral budesonide, has gained relevance, as well as immunosuppressive agents such as azathioprine and 6-mercaptopurine. The use of anti-tumor necrosis factoragents, infliximab and adalimumab, constitutes a new, interesting tool for the treatment of microscopic colitis, but larger, adequately designed studies are needed to confirm existing data.

Enhanced apoptosis in post-liver transplant hepatitis C:Effects of virus and immunosuppressants

Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an aggressive course.There is increasing evidence that in the non-transplant setting,induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis,and that HCV proteins directly promote apoptosis.Recent studies have shown that post-liver transplant,there is a link between high levels of HCV replication,enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver fibrosis.Although the responsible mechanisms remain unclear,it is likely that immunosuppressive drugs play an important role.It is well known that immunosuppressants impair immune control of HCV,thereby allowing increased viral replication.However there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV replication.Thus HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid fibrosis.These findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease.

Differential Treatment for Membranoproliferative Glomerulonephritis with TCM Prescriptions Plus Triptoryph Tablets A Report of 30 Cases

Membranoproliferative glomerulonephritis is aglomerulopathy,which accounts for about 30% of thechronic glomerulonephritis in adults.TCMmedication with addition of triptoryph tablets(Tripterygium Wilfordii polyglycosidium) on thebasis of syndrome differentiation had yieldedsatisfactory results in 30 cases of this disease treatedfrom Jan 1998 to Aug 2002.A report follows.

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma:A single-arm, multicenter, prospective study

Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.

HYPERTENSION IN RENAL ALLOGRAFT RECIPIENTS

Objective To further evaluate the effect of hypertension on renal graft function, and the relationship between hypertension, hyperlipoidemia and ischemic heart disease. Methods 102 renal transplant recipients with a functioning renal graft for more than 1 year were enrolled in this study. Renal function was followed for the further 24 months. Results The overall prevalence of hypertension was 89.2%(91/102) and 36.2%(33/91) hypertensive patients had uncontrolled blood pressure. After 24 months those with high blood pressure had significantly higher Scr levels than normotensive patients (P<0.05). The number of different antihypertensive classes required was related to Scr (P<0.05). Plasma cholesterol levels in hypertension patients especially in blood pressure uncontrolled group were significantly elevated (P<0.01). Ischemic heart disease was more common in hypertensive patients (P<0.05). Cyclosporine A was associated with hypertension more frequently than azathioprine and FK506, whereas low-dose prednisolone did not appear to influence blood pressure. Conclusion The data further confirmed that hypertension was associated with hyperlipidemia and ischemic heart disease, and emerged as a predictor of renal graft dysfunction. Whether cyclosporine A should be converted to new immunosuppressive agents and which class of antihypertensive medication is more effective in this population remain open questions.

Mycophenolate Mofetil with Low Dose CsA for Chronic Rejection in Primary Cadaveric Renal Recipients

Objective To investigate the clinical efficacy of mycophenolate mofetil(MMF) with low dose CsA for chronic rejection in primary cadaveric renal recipients. Methods A total of 8 renal recipients who were clinically diagnosed as chronic rejection were given triimmunosuppressive agents: MMF 1.5~2.0 g/d+ CsA 2 to 3 mg/kg·d -1 and pred 10 mg/d.Results Blood creatinine reduced to normal level and urine protein disappeared in five cases, blood creatinine and urine protein decreased obviously in two cases, and kidney function deteriorated in another patient 4 to 9 weeks after this strategy. No acute rejection episodes or liver damage occurred among these patients during treatment. White blood cells reduced in one case, but it improved after therapy. Conclusion MMF combined with low dose CsA can bring a considerable efficacy in reversing chronic rejection of renal recipients. This immunosuppressive strategy may be a useful routine in the treatment of chronic rejection.