Rejection Rates In Patients Research Articles

Investigating Defects of Esophageal Motility in Lung Transplant Recipients.

BackgroundLung transplant patients are at risk of developing chronic lung allograft dysfunction (CLAD) of which bronchitis obliterans syndrome (BOS) is the most common. These patients also are noted to develop gastrointestinal (GI) disease. Gastroesophageal reflux disease (GERD) is implicated in BOS, and diagnosis and treatment of GERD may help to decrease incidence of BOS.MethodsA total of 131 lung transplant recipients with post-transplant evaluation between 2012 and 2019 were studied. Of 60 post-transplant evaluations with at least 6 months of post-transplant follow-up that included impedance testing, high-resolution manometry (HRM), and pH testing, procedures were performed according to recognized standards.ResultsOf 60 patients, 56 (93%) were alive at 1-year post-transplant. The patients were found to have high rates of GI motility diseases: 37 patients (62%) had abnormal impedance testing, 50 patients (83%) had abnormal HRM results, 22 patients (37%) had abnormal pH test results. There was associated high rejection rates in patients with abnormal esophageal motility. There were 37 patients that had abnormal impedance test results and of those 25 patients (67%) developed rejection. Fifty patients had abnormal post-transplant HRM studies, 33 (66%) had an acute cellular rejection episode. Twenty-two patients had abnormal pH results, with 14 (63%) having an acute cellular rejection.ConclusionsPatients undergoing lung transplantation were found to have increased incidence of abnormal GI motility studies of the esophagus. These patients were further found to have increased rejection rates and BOS which has been associated with worsened mortality. Developing a formalized pre- and post-transplant motility study process, using evolving technologies for these patients, may provide guidance of at-risk patients for CLAD and early treatment to prevent CLAD.

CYP3A4 Polymorphisms and Acute Cellular Rejection in Lung Transplant Patients

Purpose Tacrolimus is the main component of the immunosuppressive regimen used in patients with solid organ transplants. Genetic polymorphism in CYP3A4 and CYP3A5 enzyme expression contributes to differences in tacrolimus metabolism with potential impact on allograft function. Although genetic factors influencing immunosuppressive response have been studied in kidney, heart and liver transplant patients, data regarding lung transplant patients are more limited. The aim of our study was to determine the relationship between CYP3A4 and CYP3A5 polymorphisms and acute rejection. Methods 41 lung transplant recipients were included. We retrospectively reviewed clinical and pathology data of patients. CYP3A5 polymorphisms were defined as intermediate, normal, or poor metabolizers. CYP3A4 polymorphisms were defined as rapid, intermediate, normal, or poor metabolizers. The diagnosis of acute cellular rejection was based on histopathology results. Chi-square statistic was used to compare categorical continuous variables (CYP3A5, CYP3A4 and acute rejection). Results The mean age of the patients was 59±13 years (mean ± SD) with an age range between 21 to 75 years. Among patients included in the analysis there were 51% males . There was a statistically significant increased rate of rejection in patients with normal CYP3A4 polymorphisms (68%) as compared to patients with poor and intermediate CYP3A4 polymorphisms (20%) (p 0.036). There was no association between CYP3A5 phenotype and acute rejection (p= 0.33). Conclusion Although this was a small study, our data suggest that CYP3A4 phenotype may influence the occurrence of acute rejection. Patients with normal CYP3A4 phenotype might require closer monitoring and higher tacrolimus concentrations to avoid rejection. Additional studies are needed to confirm these results and determine whether genotype-based tacrolimus dosing could improve outcomes in lung transplant recipients.

11-year experience of kidney retransplantation in elderly recipients in Sklifosovsky Research Institute for Emergency Medicine

Introduction. In spite of improvements in quality of life and lifetime of kidney transplant recipients the limited time of kidney transplant survival dictate the need for returning back to dialysis or repeat kidney transplantation. In respect that the need of repeat kidney transplantation usually observed in elderly recipients we attach importance in the analysis of outcomes of kidney retransplantation in patients over 60-s. Aim: to analyse the early outcomes of kidney re-transplantations in middle-aged and elderly recipients. Material and methods : the retrospective analysis of outcomes of 124 repeat kidney transplantations was made (16 transplantations in elderly recipients -Group I; 108 transplantations in recipients aged 20-59 yrs - Group II). The recovery of kidney transplants, acute rejection rates, the causes and the rate of kidney transplant dysfunction and failure, early patient’s and kidney transplant’ survival rates were analyzed. We used clinical, laboratory, histological and instrumental diagnostics. Results : in both groups there were no differences in kidney transplant recovery rates (p = 0,546), kidney transplant function (normal function 81,2% vs 86,1%, dysfunction 6,3% vs 4,3%, graft failure 12,5% vs 9,3% (p = 0,876), recipient 100% vs 99,1% (p = 0,34) and graft survival rates 87,5% vs 90,7% (p = 0,30). There were no episodes of acute rejection in patients of group I (0% vs 30,6% (p = 0,006). The reason of graft failure in group I - the graft’s pathology (nephroangiosclerosis (12,5%), group II - intractable acute rejection (4,6%), graft’s pathology (3,7%), patient’s death with functioning graft (0,9%). Conclusion: there were similar recipient and graft survival rates in both groups. We observed lower acute rejection rate in patients of group I using sufficient immunosuppressive regimens.

Dosing of Enteric-Coated Mycophenolate Sodium Under Routine Conditions: An Observational, Multicenter Study in Kidney Transplantation.

BACKGROUND Dosing of enteric-coated mycophenolate sodium (EC-MPS) should be adjusted to reflect concomitant immunosuppression, but it is largely undocumented whether such modifications are carried out during routine clinical practice. MATERIAL AND METHODS MyLIFE was an observational study of adult kidney-only or kidney-pancreas transplant patients starting -EC-MPS at 33 French transplant centers. Data were collected at first EC-MPS dose and 6 months later. The primary objective was to describe initial EC-MPS dosing according to concomitant immunosuppression. RESULTS There were 461 patients analyzed (174 started EC-MPS by month 1 post-transplant ['de novo'] and 287 started EC-MPS >1 month post-transplant ['maintenance']), receiving cyclosporine (CsA) (n=76), tacrolimus (n=363), or a mammalian target of rapamycin (mTOR) inhibitor (n=22). Mean (SD) starting dose was 1130 (511) mg/day, 1006 (441) mg/day, and 769 (300) mg/day in the CsA, tacrolimus, and mTOR inhibitor groups, respectively (p=0.003). In the de novo subpopulation, the starting dose was 1440 mg/day in 66.7% (14/21) of CsA-treated patients and 71.9% (110/153) of tacrolimus-treated patients, with an intensified dose of 2160 mg/day in 28.6% (6/21) and 8.5% (13/153), respectively. There was a non-significant trend to a higher rate of biopsy-proven acute rejection in patients receiving CsA versus tacrolimus or an mTOR inhibitor (p=0.082). Adverse events with a suspected relation to EC-MPS occurred in 21.0%, 23.1%, and 9.1% of the CsA, tacrolimus, and mTOR inhibitor subpopulations, respectively. CONCLUSIONS EC-MPS is usually initiated at the dose recommended for de novo CsA-treated kidney transplant patients, then titrated downwards as required. An early intensified regimen is not used frequently. The EC-MPS dose is modified in <20% of de novo patients to account for concomitant tacrolimus therapy instead of CsA administration.

Resultados funcionales de la procuración corneal con fines de trasplante realizado por un licenciado en Optometría

IntroductionIn Mexico, availability of donated corneas is very low. In recent years there has been a decrease in corneal tissue importation creating a need in tissue harvesting among public hospitals. Due to a shortage of available ophthalmologists, trained optometrist could cover adequately this rising need. AimsTo analyze quality of corneal tissue harvested by a trained optometrist and to identify long term functional results in visual acuity and graft rejection rate in patients receiving those corneal tissues. MethodsPatients who received corneal tissues harvested by a single optometrist from January 2011 to November 2012 were included. Endothelial density was measured with specular microscopy. Initial and final visual acuity was measured using Snellen chart. Graft rejection presence was identified in all transplanted patients. Descriptive statistics was performed with Stata 10.0 Results25 corneas were harvested. 4 non-viable corneal tissues were discarded. 21 patients underwent corneal transplantation Mean preoperative endothelial cell count was 2834.76 cel/mm2 (SD±186.91). Three patients (3 tissues) (14.28%) had graft rejection. Mean preoperative visual acuity was 1.24 LogMar (SD±0.2923). All patients had visual acuity improvement in their last eye examination (p<.001) with a mean visual acuity of 0.52 LogMar (SD±0.3792). Mean follow-up was 34.85 months (SD±3.6). ConclusionsAll patients in this study had improvement in their final visual acuity. Corneal graft rejection rate was similar to frequency reported elsewhere. Trained optometrist could be ideal health professional to harvest donor corneas.

A COMPARATIVE ANALYSIS OF BIOEQUIVALENCE, CLINICAL EFFICACY AND SAFETY OF GENERIC VERSUS ORIGINAL CYCLOSPORINE AFTER KIDNEY TRANSPLANTATION

The aim of the study was the evaluation of pharmacokinetic parameters and clinical efficacy of generic cyclosporine (Ecoral) and Sandimmune Neoral. Materials and methods’ . The pharmacokinetic parameters of different cyclosporine formulations. In 197 kidney graft recipients 319 comprehensive pharmacokinetic studies were performed. In 42 patients received in consecutive order original and generic Cyclosporine in the same dosage the complete pharmacokinetic study was perforfomed. AUC calculations based on dosing interval concentration values were fulfilled using linear trapezoidal rule. To evaluate clinical efficacy 235 short pharmacokinetic studies with concentration examination at 0, 1, 2 and 3 hours after taking Cyclosporine (Co, C1 C2 and C3) were performed in patients treated with Neoral (n = 75) or generic cyclosporine (n = 160). Clinical efficacy of generic cyclosporine was estimated by the prevalence of allograft dysfunction and biopsy proved acute rejection episodes as well as by one-years graft survival and events-free survival. The graft survival rate was calculated by Kaplan–Meyer method. Results . At 100–200 ng/ml maintenance concentration (estimated by C0 concentration) pharmacokinetic parameters did not significantly differ according to Cyclosporine formulation in both complete or short pharmacokinetic studies: AUC-4265 vs. 4204 and 3834 vs. 3670 ng/ml/h respectively; (p &gt; 0.05), Cmax (1036 vs 931 and 813 vs 741 ng/ml respectively; (p &gt; 0.05). Allograft dysfunction occurred in 5% of patients subjected to Neoral immunosuppression and in 8% of Equoral recipients (p &gt; 0.05). However biopsy-proven acute rejection as a cause of graft dysfunction was seen only in patients receiving Ecoral (7% vs 0; p &lt; 0.05). One-years graft survival rate did not differ between groups (99% and 94% in generic CyA and Neoral respectively; p &gt; 0.05), whereas events-free graft survival was significantly lower in patients, receiving generic CyA than in Neoral group (88 vs 94% respectively; p = 0,03). Conclusion . Pharmacokinetic studies have shown the absorption profile of generic formulations Equoral do not differ significantly from that of Neoral. Prospective pilot trial demonstrated no difference between one-year graft survival or graft dysfunction rate, but lower eventsfree one-year graft survival as well as the tendency to higher acute rejection rate in patients treated with generics in comparison with those receiving Neoral should be noted. This issue is to be studied further.

Sirolimus in Intestinal Transplantation: Single Center Experience Over a Decade.

Background. Standard maintenance immunosuppression after intestinal transplantation (ITx) currently consists of tacrolimus-based regimens. We previous reported that adding sirolimus significantly reduces rejection rates and graft loss. We now present our decade-long experience with sirolimus in ITx. Patients. 160 patients (87M 73F, n=80 adults (median age 42 y [18-66], n=80 children (median age 1.6 y [6 mo-17.5 y] undergoing primary ITx (87 isolated small intestine, 44 liver-intestine, 24 multivisceral and 5 modified MV) between 2003 and 2013 with a follow-up ≥3 months were reviewed. Immunosuppression consisted of induction (depleting/ non-depleting) and maintenance with tacrolimus, sirolimus and steroids. Rejection was diagnosed on endoscopic biopsies according to standard histology criteria. Results. Overall 56 (35%) patients experienced a total of 82 rejection episodes (mild n=34, moderate n=14, severe n=34) at a median of 56 days (15-1801) after Itx. 121 (75%) patients were treated with sirolimus. Of those, 103 pts (85%) discontinued sirolimus (temporarily (n=17), or permanently (n=86) after a median of 50 days (2-1575) due to infection (45%) nephrotoxicity (33%) and other complications (22%). Regardless of the treatment duration, the rejection rate in patients treated with sirolimus was significantly lower than non-treated patients (29.9% vs.50.9% [p=0.0094]).Figure: No Caption available.Unconditional 1-year (88% vs.74% p=0.027) and 5-year (78% vs 67% p=0.061) patient survival was higher in subjects treated with sirolimus. Conclusion This is the first single center large series of ITx recipients treated with sirolimus over a decade. We confirm our prior report that adding sirolimus to tacrolimus significantly improves outcomes in ITx, leading the way to establish the combination of CNI and mTOR inhibitor as the new paradigm in immunosuppression after ITx.

Tacrolimus Induces Glomerular Injury via Endothelial Dysfunction Caused by Reactive Oxygen Species and Inflammatory Change

Background/Aims: The immunosuppressive drug tacrolimus (FK506) is used clinically to reduce the rejection rate in patients with kidney transplantation; however, the resultant nephrotoxicity remains a serious problem. In the present study we attempted to elucidate the mechanisms of glomerular injury induced by FK506 and the renoprotective effects of the angiotensin II receptor blocker telmisartan. Methods: Seven-week-old male Wistar rats were divided into three groups: vehicle group, FK506 group, and FK506 + telmisartan group. After 8 weeks, we assessed kidney function and renal morphological changes including oxidative stress. We also assessed the effect of FK506 in human glomerular endothelial cells (hGECs) with regard to reactive oxygen species (ROS). Results: FK506 induced ROS production via activation of NAD(P)H oxidase in the glomeruli. Expression of ICAM mRNA was increased in glomeruli from the FK506 group. These effects resulted in macrophage infiltration into the glomeruli. FK506 directly promoted NAD(P)H oxidase activity and accelerated production of ROS in hGECs. Conversely, cotreatment with telmisartan inhibited both NAD(P)H oxidase activity and production of ROS. Conclusion: These findings suggest that glomerular injury resulting from FK506 is caused by oxidative stress mediated by activation of NAD(P)H oxidase and that telmisartan exerts a renoprotective effect via antioxidative activity.

Lower tacrolimus daily dose requirements and acute rejection rates in the CYP3A5 nonexpressers than expressers

CYP3A5 genetic polymorphisms contribute to marked interindividual differences in the metabolism of and response to tacrolimus in humans. This study was aimed to clarify the impact of the CYP3A5*3 variant on tacrolimus dose requirements and acute rejection rates in patients with organ transplantation. A literature search was performed up to August 2009 by using the Cochrane library, PubMed, Medline, and EMBase. Twenty-three studies (a total of 1779 patients) were included in this meta-analysis. Eighteen studies (1443 patients) were involved in renal transplantation and five studies (336 patients) in liver transplantation. Results of meta-analysis demonstrated that, in renal transplant patients, despite the presence of significant heterogeneity, CYP3A5 expressers required higher mean tacrolimus daily doses by 0.045 mg/kg (95% confidence interval (CI), 0.033-0.056) than nonexpressers. Furthermore, sub-analysis of the time of posttransplantation showed that CYP3A5 expressers required higher daily doses than nonexpressers by 0.010, 0.084, 0.041, 0.037, and 0.044 mg/kg at week 2, and at month 1, 3, 6, and 12, respectively. Subset analysis of the ethnicity of organ recipients indicated that mean tacrolimus daily doses were 0.056, 0.037, and 0.077 mg/kg higher in CYP3A5 expressers than non- expressers for white, Chinese, and Japanese patients, respectively. In contrast, for liver transplant patients, higher tacrolimus daily doses were required not only in CYP3A5 expressers of the organ donors than nonexpressers by 0.024 mg/kg (95% CI, 0.019-0.028), but also in CYP3A5 expresser of the organ recipients than nonexpresser by 0.012 mg/kg (95% CI, 0.005-0.018). However, a significant difference in the acute organ rejection rate was observed only at one month (odds ratio, 3.27; 95% CI, 1.57-6.81; P=0.002). Tacrolimus daily dose requirements may vary with the presence of the CYP3A5*3 variant, ethnicity of the organ recipients, and the time of posttransplantation. In addition, the acute organ rejection rate may be higher in CYP3A5 expressers than nonexpressers over the first month after transplantation.

COMPARACIÓN DEL RECHAZO AGUDO DURANTE EL PRIMER AÑO DEL INJERTO EN PACIENTES TRASPLANTADOS RENALES QUE RECIBIERON BASILIXIMAB O DACLIZUMAB. HOSPITAL CALDERÓN GUARDIA. PERÍODO 2000-2008

Antecedentes El rechazo agudo del injerto es unacomplicacion importante en pacientes sometidosa trasplante renal. El presente estudio buscacomparar el porcentaje de rechazo agudo delinjerto en el primer ano del trasplante renal alhaber recibido daclizumab o basiliximab comoinductor de inmunosupresion. Metodos Es un estudio observacional de cohorteretrospectivo y comprende el periodo de enero de2000 hasta diciembre de 2008. Fue realizado enel Servicio de Nefrologia del Hospital Calderon Guardia. La poblacion fue aquellos pacientestrasplantados renales en el Hospital Calderon Guardia y que recibieron basiliximab o daclizumab como inductor de inmunosupresion. Resultados La presencia de rechazo agudo delinjerto se presento con mayor frecuencia en el grupo que recibio basiliximab comparado con elde daclizumab. Discusion La proporcion de rechazo agudo delinjerto renal durante el primer ano del trasplanteen el Hospital Calderon Guardia presento diferencias entre los pacientes tratados con daclizumab y los tratados con basiliximab. En esteultimo grupo hubo mas rechazo.

Corneal graft rejection in African Americans at Howard University Hospital

Purpose There is scarcity of data in the literature on cornel graft rejection rate in patients exclusively of African ancestry. The purpose of this study was to evaluate the rejection rate of corneal transplant surgery performed at Howard University Hospital on such patients over a 15 year period. Design A retrospective evaluation was performed of the cornea graft rejection and corneal graft failure rate in 125 penetrating keratoplasties (PKPs) done by one corneal specialist at Howard University Hospital from January 1, 1990 to August 31, 2005. Methods Of the 125 patients, 62 were eliminated from the study because of re-grafted eyes, non-African descent, primary graft failures, follow-up less than 1 month and lack of availability of charts. This study, therefore, studied and recorded data from 63 penetrating keratoplasties of 63 eyes from 60 patients. Results Episodes of graft rejection were documented in 23 eyes (36.5% of cases). Nine out of the 23 graft rejections manifested to secondary graft failure (39%). Overall, there were nine out of the 63 PKPs (14.3%) that resulted in secondary graft failure over the past 15 years. The major diagnostic categories were bullous keratopathy 24 (38%), keratoconus 10 (15.8%), Fuch’s dystrophy 4 (6.3%), other 20 (31.7%). Of the cases with episodes of rejection and failure, 4.3% and none were attributable to keratoconus, 30.4% and 22.2% for bullous keratopathy, and 8.7% and 22.2% for Fuch’s dystrophy, respectively. Also, best visual acuity was looked at in patients with rejection episodes. None of the patients had a pre-op visual acuity 20/40 or better; however, post-op PKP 2 (8.7%) of patients achieved 20/40 or better. Also, 4 (17.4%) of patients had a pre-op visual acuity between 20/50 and 20/150, but post-op PKP best visual acuity between 20/50 and 20/150 was increased to 9 (39.1%). Conclusion At 36% the prevalence of corneal graft rejection was one of the highest in the reported literature. But only 14% of those episodes resulted in graft failure which is one of the lowest in the published literature. This study demonstrates that patients of African ancestry may have a higher rejection rate which does not necessarily result in graft failure.

New protocol reduces acute renal allograft rejection rate in patients with HIV

New protocol reduces acute renal allograft rejection rate in patients with HIV

Short-term versus long-term induction therapy with antithymocyte globulin in orthotopic liver transplantation

T-cell depletion is an essential aspect of clinical immunosuppression. The aim of the present study was to compare the efficacy of two dosage regimens in this setting. We retrospectively compared 246 patients (group 1) who received a 10-day antithymocyte globulin (ATG) induction protocol with 226 patients (group 2) who received a 3-day protocol. The 6-month rejection rate was 22.3% in group 1 and 12.7% in group 2 (P = 0.03). The sub-analysis showed a higher rejection rate in patients with cholestatic disease (P = 0.01), who were more numerous in group 1. This resulted in an overall difference between the groups. Rates of de novo malignancies and recurrent hepatocellular carcinoma were identical. Viral infection rates were 16% and 18%, respectively (P > 0.5). The rates of bacterial and fungal infection were also similar (37% vs. 42%, P > 0.1). However, infection and ATG administration are independent risk factors for survival. A lower rate of fatal infection was observed in group 2 (P = 0.01), while the 10-day ATG regimen had a detrimental effect on patients who had infection (P < 0.0001). Our results strongly support the application of 3-day ATG induction therapy regimen after orthotopic liver transplantation, as it is associated with the same rejection rate as long-term ATG induction therapy, without the negative survival effect of the latter due to lethal infection.

Long-Term Graft Outcome with Mycophenolate Mofetil and Azathioprine: A Paired Kidney Analysis

Randomized controlled trials and U.S. Registry data have demonstrated that mycophenolate mofetil (MMF) reduces acute rejection rates and improves graft survival. We undertook the first paired kidney analysis comparing the effects of MMF and azathioprine on graft outcome in the United Kingdom. In all, 238 deceased donors from 1999 to 2002 who donated one kidney to a patient treated with MMF and the other kidney to a patient treated with azathioprine were identified from the national transplant database held by U.K. Transplant. Graft function and rates of change of graft function were compared using multiple linear regression analyses adjusting for covariates on an intention-to-treat basis. Incidence of acute rejection and delayed graft function were studied using logistic regression. Patient and graft survival censored for death were evaluated with Cox regression analyses. The MMF-treated patients exhibited a nonsignificant trend towards improved graft function but with increased rejection rates (44% versus 31%, P < 0.01). Treatment with MMF did not reduce delayed graft function rates. Univariate analysis showed that graft survival was inferior in MMF-treated patients (90% versus 95%, log-rank, P = 0.02) but in multivariate Cox regression models, MMF treatment was not a significant factor. Surprisingly, in the first year 32% of patients achieved daily doses of less than 2 g of MMF compared to 18% of patients who received less than 100 mg of azathioprine (P < 0.01). In this real-life study, there was no difference in patient or graft outcome between MMF and azathioprine treated groups despite increased rejection rates in patients receiving MMF therapy.

ABO-Incompatible Kidney Transplantation with and without Splenectomy

The letter to the editor from Dr. Mitsuhata et al. raises interesting points with regard to the role of splenectomy in ABO-incompatible (ABOI) kidney transplants. The authors contend that the classification of ABOI kidney transplant recipients as “high risk” should not be made on the basis of baseline antibody titer. The association of humoral rejection with baseline antidonor blood group antibody titer in splenectomized ABOI recipients not undergoing posttransplant plasmapheresis has been reported by Shimmura et al., who found a 70% humoral rejection rate in patients with baseline titer ≥128 and 20% in those with titers ≤1:64 (1). These findings are similar to those of our report in which rejection occurred in 12% of patients with titers <1:64, while 83% of those with titers exceeding 1:64 rejected (2). Interestingly, Shimmura et al. have recently reported that posttransplant plasmapheresis to maintain a low titer in conjunction with splenectomy is effective in preventing humoral rejection in ABOI recipients with very high baseline titers (3). In their letter, Mitsuhata et al. refer to their Brief Communication describing their use of mycophenolate mofetil during four weeks preceding ABOI transplantation in 18 patients compared to 18 patients who did not receive pretransplant mycophenolate mofetil (4). In their report, all patients underwent antibody lowering therapy with plasmapheresis or plasma exchange. No comment was made as to whether or not recipients underwent splenectomy, although their current letter to the editor implies that they did. They report improved allograft survival six months after transplant in the pretreated group, although the humoral rejection rate was comparable. The causes for allograft loss in the pretreatment group were not reported, nor were baseline antidonor blood group antibody titers. The authors indicate that on the day of transplantation antidonor blood group antibody titers ranging from 1–128, although not specifically reported. Given our admittedly smaller experience in ABOI kidney transplantation, we would be very reluctant to proceed to transplantation at the time the recipient's titer exceeded 1:16, and our practice is to continue to perform plasmapheresis until achieving a titer ≤1:8 on the day of transplantation. An important point is that the antibody titer depends strongly on the method used to measure it. It is possible that the antibody measurement technique used by Mitsuhata et al. differs from the technique reported in our investigation. The authors present their opinion that the benefits of transplantation without splenectomy are outweighed by the psychological, physical, and economic burden posed by posttransplant plasmapheresis and/or anti-CD20 antibody therapy. Our opinion is that with aggressive posttransplant antibody monitoring and therapy to maintain low titer during the first two weeks after transplantation, humoral rejection is an unusual complication in the large majority of ABOI kidney transplants. We also feel that the life long advantage of avoiding splenectomy exceeds the disadvantage of posttransplant therapy during the first one to two weeks after transplantation. Finally, the authors refer to the important fact that other potentially injurious antibodies with donor reactivity may also complicate ABOI transplantation, similar to ABO compatible transplants, and we agree. James Gloor Department of Internal Medicine and Nephrology Mayo Clinic Rochester, MN Mark Stegall Division of Transplantation Surgery Mayo Clinic Rochester, MN

Treatment with atorvastatin alters the ratio of interleukin‐12/interleukin‐10 gene expression

BACKGROUND Statins have been shown to have pleiotropic effects extending beyond their ability to lower cholesterol. MATERIAL AND METHODS Seventeen patients with heterozygous familial hypercholesterolaemia participated in a single-blind placebo controlled study. The patients underwent three treatment regimens: placebo (4 weeks), atorvastatin 10 mg day(-1) (4 weeks) and atorvastatin 40 mg day(-1) (12 weeks). Following each treatment period, serum lipids and plasma mevalonic acid were measured, mononuclear leukocytes were isolated and total RNA was prepared. The content of mRNA for IL-12p35 and IL-10 was assayed, blinded, by real-time quantitative polymerase chain reactions. RESULTS Treatment of the subjects with atorvastatin decreased the abundance of IL-12p35 mRNA in mononuclear cells, but did not alter that of IL-10, so that the ratio of the IL-12p35 to IL-10 mRNA content was significantly reduced (P < 0.0026). The IL-12p35/IL-10 ratio correlated significantly with plasma mevalonic acid concentrations but not with serum LDL concentrations. CONCLUSIONS This study provides evidence that atorvastatin exerts an immunomodulatory effect in vivo, characterized by a decrease in the ratio of IL-12 mRNA to IL-10 mRNA in leukocytes. The immunomodulatory effect of statins, in addition to their cholesterol-lowering properties, may contribute to the rapid cardiovascular benefit observed during treatment with statins and reduced the rate of rejection in patients with solid organ transplantation.

Successful outcome of orthotopic liver transplantation in patients with preexisting malignant states.

Preexisting malignancy is considered a relative contraindication to orthotopic liver transplantation (OLT) because of the risk of tumor recurrence. The purpose of this study is to assess the outcome of OLT in patients with a preexistent malignant state. Of 1,097 OLTs performed between 1989 and 1999 at King's College Hospital (London, UK), 18 patients had a pretransplantation malignant state, including 6 cases of myeloproliferative disorder (MPD) presenting as Budd-Chiari syndrome. Those patients with solid-organ malignancies had their tumor detected at an early stage and underwent curative treatment before or during OLT. Patients were followed up for a median of 71 months (range, 1 to 119 months) post-OLT, and the rates of rejection and malignancy were compared with those of transplant recipients without preexisting malignancy during the same period. One patient had a recurrence of his primary malignancy (non-Hodgkin's lymphoma) after 27 months, whereas another patient developed a de novo posttransplant lymphoproliferative disorder after 57 months. One patient with MPD developed acute leukemia 72 months after OLT. In comparison, of 1,079 OLTs performed in patients without preexisting malignancy during the same period, there were 34 cases of de novo malignancies. The rate of rejection in patients with and without preexisting malignancy was similar. Successful medium-term outcome after OLT can be achieved in carefully selected patients with preexisting malignancy providing the malignancy is amenable to curative treatment before or at OLT. Primary MPDs responsible for Budd-Chiari syndrome should not be considered a contraindication to OLT.

Daclizumab

The humanised monoclonal antibody daclizumab is an immunosuppressive agent that reduces acute rejection in renal transplant recipients. It is specific for the alpha subunit (Tac/CD25) of the interleukin-2 (IL-2) receptor on activated T cells and achieves immunosuppression by competitive antagonism of IL-2-induced T cell proliferation. Daclizumab has advantages over murine antibodies to the IL-2 receptor, including improved effector function, a low potential for immunogenicity and long elimination half-life. When added to standard cyclosporin-based immunosuppressive therapy with or without azathioprine, daclizumab (1 mg/kg prior to surgery and once every 2 weeks thereafter for a total of 5 doses) significantly reduced the 6-month rate of acute rejection compared with placebo in 2 phase III studies. The mean number of rejection episodes was significantly reduced and the time to first acute rejection significantly increased in daclizumab versus placebo recipients. Patient survival at 1 year after transplantation was significantly higher with daclizumab than placebo in 1 study and showed a trend in favour of the drug in the other study. The 1-year graft survival rate tended to be greater in daclizumab than in placebo recipients in both studies, In a phase II study, acute rejection rates in patients treated with both daclizumab and mycophenolate mofetil (plus standard cyclosporin-based immunosuppression) were lower than those achieved with mycophenolate mofetil alone. Preliminary results indicate that daclizumab is also a useful agent in paediatric renal transplant recipients. Further investigation of the efficacy and tolerability of the drug in this patient group is clearly warranted. Daclizumab does not increase the incidence of adverse events when added to standard cyclosporin-based therapy. The incidence of opportunistic infections, lymphoproliferative disorders and malignancies was not increased above that seen with placebo. Although the effects of daclizumab on long term graft and patient survival require further investigation, available data indicate that daclizumab is an important advance in renal transplant immunosuppression, reducing acute graft rejection without affecting the tolerability of standard cyclosporin-based immunosuppression.