Steroid-free Immunosuppressive Regimen Research Articles

Long-term outcomes of two-dose alemtuzumab induction in pediatric kidney transplantation.

Alemtuzumab is a lymphocyte depleting agent used for induction in kidney transplant, but long-term information on its use in pediatric recipients remains sparse. We performed a single-center retrospective cohort study of 57 pediatric kidney transplant recipients receiving alemtuzumab 20 mg/m2/dose ×2 doses for induction immunosuppression. All patients underwent surveillance biopsies, and 91.3% underwent steroid withdrawal by day 4 post-transplant. Outcomes of interest included graft survival, development of donor specific antibodies (DSA), incidence of viremia and PTLD, and duration of lymphopenia. Median follow-up time was 7.9 years (IQR 5-13.6 years). Median graft survival was 16.5 years (95% CI 11.6-unknown). DSA developed in 36.5% at a median of 944 days (IQR 252-2113 days). Incidences of BK polyomavirus DNAemia (BKPyV-DNAemia), CMV DNAemia, and EBV DNAemia were 38.6%, 22.8%, and 14%, respectively; one patient developed PTLD at 13.3 years post-transplant. Median duration of lymphopenia was 365 days (IQR 168-713 days); 19.3% of patients remained lymphopenic at 3 years post-transplant. There was no association between duration of lymphopenia and graft survival, rejection, DSA detection, or viremia. A two-dose alemtuzumab induction protocol can have excellent outcomes with a steroid-free maintenance immunosuppression regimen. More comprehensive, multicenter, comparative studies of pediatric kidney transplant are needed to improve long-term outcomes.

COVID-19 Outcomes in Kidney Transplant Recipients in a German Transplant Center.

Kidney transplant recipients (KTRs) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTRs. Between 1 February 2020 and 1 July 2022, 578 KTRs were infected with SARS-CoV-2, with 25 (4%) recurrent infections. In total, 208 KTRs (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed that being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas a steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both virological changes in the Omicron variant and vaccination reduce the risk for morbidity and mortality from COVID-19 in KTRs. Our data extend the knowledge from the general population to KTRs and provide important insights into outcomes during the Omicron era.

Effects of Corticosteroid Treatment on Mycophenolic Acid Exposure in Renal Transplant Patients-Results From the SAILOR Study.

Background: Mycophenolic acid (MPA) is a potent immunosuppressive agent used in solid organ transplantation. MPA exhibits large interindividual variation in dose-normalized plasma concentrations but is nevertheless usually prescribed as a fixed dose without use of therapeutic drug monitoring (TDM). Data on the effect of corticosteroid (CS) treatment on MPA concentrations during concomitant tacrolimus treatment remains sparse.Methods: Data is based on TDM of MPA area under the concentration curve (AUC) in 210 renal transplant recipients participating in the prospective, randomized, controlled, multi-center trial (SAILOR) where a steroid-free immunosuppressive regimen with mycophenolate mofetil (MMF) and low-dose tacrolimus was compared with a conventional prednisolone-based treatment regimen. Multilevel mixed-effects linear regression post-hoc analyses of MPA AUC was performed.Results: Median MPA AUC at baseline (within the first 2 weeks post-transplant) in patients taking 2 g MMF daily was 53 mg*h/L (interquartile range: 43–69 mg*h/L, min: 24—max: 117 mg*h/L). Between-patient variation in MPA AUC was up to 5-fold on the same MMF dose. Patients in the steroid-free group had 12.5% lower (95% CI; 3.2–20.9%, p = 0.01) MPA AUC levels at baseline compared to the steroid treated group. During follow-up (14 days–2 years post-transplant) there were no significant differences in MPA AUC between the groups with MPA AUC being 4.2% lower (95% CI: −4.8%−12,5%, p = 0.35) in the steroid-free vs standard treatment group in restricted analysis after multivariate adjustment for tacrolimus trough level, body weight, time after transplantation and MMF dose. MMF dose was positively correlated with MPA AUC (p < 0.001) whereas body weight was negatively correlated with MPA AUC (p < 0.001). MPA AUC was 0.4% (95% CI: 0.2–0.6%, p < 0.001) lower per 1 kg increase in weight. Tacrolimus trough levels had no significant effect on MPA AUC.Conclusion: Immunosuppression with CS during concomitant tacrolimus treatment was shortly after transplantation associated with a significantly higher MPA exposure but the effect was small and not maintained during follow-up. Low body weight was associated with higher MPA exposure, which suggests a potential for weight adjusted MMF dosing.

Association of HLA Typing and Alloimmunity With Posttransplantation Membranous Nephropathy: A Multicenter Case Series

Posttransplantation membranous nephropathy (MN) represents a rare complication of kidney transplantation that can be classified as recurrent or de novo. The clinical, pathologic, and immunogenetic characteristics of posttransplantation MN and the differences between de novo and recurrent MN are not well understood. Multicenter case series. We included 77 patients from 5 North American and European medical centers with post-kidney transplantation MN (27 de novo and 50 recurrent). Patients with MN in the native kidney who received kidney allografts but did not develop recurrent MN were used as nonrecurrent controls (n= 43). To improve understanding of posttransplantation MN, we compared de novo MN with recurrent MN and then contrasted recurrent MN with nonrecurrent controls. Compared with recurrent MN, de novo MN was less likely to be classified as primary MN (OR, 0.04; P< 0.001) and had more concurrent antibody-mediated rejection (OR, 12.0; P< 0.001) and inferior allograft survival (HR for allograft failure, 3.2; P= 0.007). HLA-DQ2 and HLA-DR17 antigens were more common in recipients with recurrent MN compared with those with de novo MN; however, the frequency of these recipient antigens in recurrent MN was similar to that in nonrecurrent MN controls. Among the 93 kidney transplant recipients with native kidney failure attributed to MN, older recipient age (HR per each year older, 1.03; P= 0.02), recipient HLA-A3 antigen (HR, 2.5; P= 0.003), steroid-free immunosuppressive regimens (HR, 2.84; P< 0.001), and living related allograft (HR, 1.94; P= 0.03) were predictors of MN recurrence. Retrospective case series, limited sample size due to rarity of the disease, nonstandardized nature of data collection and biopsies. De novo and recurrent MN likely represent separate diseases. De novo MN is associated with humoral alloimmunity and guarded outcome. Potential predisposing factors for recurrent MN include recipients who are older, recipient HLA-A3 antigen, steroid-free immunosuppressive regimen, and living related donor kidney.

Allo- and auto-percutaneous intra-portal pancreatic islet transplantation (PIPIT) for diabetes cure and prevention: the role of imaging and interventional radiology.

Although the life expectancy of patients with type 1 diabetes mellitus (T1DM) has improved since the introduction of insulin therapy, the acute life-threatening and long-term complications from diabetes mellitus are significant causes of both mortality and morbidity. Percutaneous intra-portal pancreatic islet transplantation (PIPIT) is a minimally invasive, repeatable procedure which allows a β-cell replacement therapy through a liver islet engraftment, leading to insulin release and glycaemic control restoration in patients with diabetes. Allo-PIPIT, in which isolated and purified islets from cadaveric donor are used, does not require major surgery, and is potentially less expensive for the recipient. In case of long-term T1DM, islet-after-kidney (IAK) transplantation can simultaneously cure diabetes and chronic renal failure, while islet-transplant-alone (ITA) is performed in brittle, short-term T1DM, based on the infusion of an adequate islet mass and on a steroid-free immunosuppressive regimen according to the Edmonton protocol. Results of the Collaborative Islet Transplant Registry (CITR) demonstrate that allo-PIPIT reduces episodes of hypoglycemia and diabetic complications, and improves quality of life of diabetic patients. Auto-PIPIT, in which the own patient's islets are used, has been investigated as a preventive treatment for pancreatogenic diabetes in patients who undergo extensive pancreatectomy for malignant and non-malignant disease. This Review outlines the role of imaging and interventional radiology in allo- and auto-PIPIT.

Clinical efficacy of steroid-free immunosuppressive regimen after liver transplantation for patients with primary liver cancer

Objective To study the clinical efficacy of steroid-free immunosuppressive therapy after liver transplantation in patients with primary liver cancer. Methods A retrospective study was conducted on the clinical data from January 2010 to October 2016 on 112 patients with primary liver cancer. There were 59 patients who had no steroid immunosuppressive regimen after operation, and 53 patients were in the steroid group. The immunosuppressive regimen used in the postoperative steroid-free group was tacrolimus + mycophenolate mofetil + basiliximab. For the steroid group it was: tacrolimus + mycophenolate moxibustion. The steroid was reduced daily in the first day after transplantation and was discontinued 3 months after transplantation. Follow-up observation of the differences between the two groups of patients on rejection, infection, tumor recurrence, hepatitis B virus recurrence and survival were compared. Results The infection rate was 18.6% in the postoperative steroid-free group, which was significantly lower than that in the steroid group (37.7%, P 0.05). Conclusions The use of the steroid-free immunosuppressive regimen in patients with hepatocellular carcinoma after transplantation was safe and did not increase the incidence of acute rejection. The regimen reduced the incidences of postoperative infection and hepatitis B virus recurrence, especially in patients who exceeded the Milan Criteria. It reduced the risk of tumor recurrence and improved patient survival. Key words: Primary liver cancer; Liver transplantation; Basiliximab; Glucocorticoid

Liver transplantation for biliary atresia: A nationwide investigation from 1996 to 2013 in mainland China.

We investigated the overall situation of LT for BA in mainland China and analyzed their survival outcomes based on data from CLTR. Between January 1996 and December 2013, 509 liver transplants for BA were performed in mainland China and were included in this study. Patients' median age was 9.6 months (range: 4.8-175.2 months). KP was previously performed in 194 cases (38.1%). Grafts from living donors were used in 380 cases (74.7%). Era I (1996.1-2010.12) and era II (2011.1-2013.12) comprised 151 cases (29.7%) and 358 cases (70.3%), respectively. Twenty-five centers had performed at least one liver transplant for children with BA. Centers from Shanghai (197 cases), Tianjin (143 cases) and Beijing (81 cases) involved 82.7% of the 509 cases. One- and five-yr graft survival rates were 84.7% and 72.6%, respectively. Split grafts, center volume <20, GRWR ≥4.0%, and steroid-free immunosuppression regimen were independent risk factors for graft survival. In conclusion, the dramatic expansion of pediatric liver transplant programs in mainland China has enabled improved survival for those children affected by this devastating disease. However, screening of BA in neonates should be emphasized throughout the country to enhance early referrals for KP.

Validation of Steroid-Free Immunosuppression Regimen after Liver Transplantation

C l i n M e d International Library Citation: Fukumitsu K, Hammad A, Kaido T, Ogawa K, Fujimoto Y, et al. (2015) Validation of Steroid-Free Immunosuppression Regimen after Liver Transplantation. J Clin Gastroenterol Treat 1:008 Received: October 15, 2015: Accepted: November 25, 2015: Published: November 27, 2015 Copyright: © 2015 Fukumitsu K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Fukumitsu et al. J Clin Gastroenterol Treat 2015, 1:2

Long-Term Study of Steroid Avoidance in Renal Transplant Patients: A Single-Center Experience

ObjectivesSteroids have played a major role in renal transplantation for more than 4 decades. However, chronic use of steroids is associated with many comorbidities. This study aimed to assess the costs and benefits of a steroid-free immunosuppression regimen in a prospective randomized controlled study of living-donor renal transplantation, which was lacking in the literature. Materials and MethodsIn our study, 428 patients were enrolled to receive tacrolimus (Tac), mycophenolic acid (MPA), basiliximab (Simulect, Novartis, Basel, Switzerland) induction and steroids only for 3 days (214 patients, study group) and steroid maintenance (214 patients, control group). Median follow-up was 66 ± 41 months. ResultsWe found that both groups showed comparable graft and patient survival, rejection episodes, and graft function. Posttransplantation hypertension was detected in 40% of the steroid-free group and 80% of the steroid maintenance group (P = .05), whereas posttransplantation diabetes mellitus was detected in 5% and 15% of these 2 groups, respectively (P = .3). ConclusionsAmong low-immunological-risk recipients of living-donor renal transplants, steroid avoidance was feasible, safe, and had less morbidity outcome using Simulect induction, then Tac and MPA as maintenance immunosuppression. Steroid avoidance was associated with a lower total cost despite comparable immunosuppression cost, which was attributed to the lower cost of associated morbidities.

Kidney transplantation in HIV-positive patients treated with a steroid-free immunosuppressive regimen.

One of the main concerns associated with renal transplantation in HIV-infected patients is the high risk of acute rejection, which makes physicians reluctant to use steroid-free immunosuppressive therapy in this subset of patients. However, steroid therapy increases cardiovascular morbidity and mortality. The aim of this study was to define the efficacy of a steroid-sparing regimen in HIV-infected renal transplant recipients. Thirteen HIV-infected patients were consecutively transplanted. The induction therapy consisted of basiliximab and methylprednisolone for 5days followed by a calcineurin inhibitor plus mycophenolate acid. The mean follow-up was 50±22months. Eight patients (61.5%) experienced acute rejection, and 75% of the first episodes occurred within 2months after transplantation. The probability of first acute rejection was 58% after 1year and 69% after 4years. Seven of eight patients recovered or maintained their kidney function after antirejection therapy and steroid resumption. At the last follow-up, seven of 13 patients (54%) had resumed steroid therapy. The 4-year patient and graft survivals were 100% and 88.9%, respectively. The benefits of this steroid-free regimen in HIV-infected renal recipients must be reconsidered because of the high rate of acute rejection. New immunosuppressive steroid-free strategies should be identi-fied in this set of patients.

Optimal use of corticosteroids in nephrology

Abstract The usage of corticosteroids is widespread in nephrology both in the treatment of patients with native kidney diseases and of patients who have received a kidney transplant. In glomerular diseases, steroids are part of most immunosuppressive regimens applied nowadays, and only few steroid-free immunosuppressive regimens have been reported on. It is my hope that - with the introduction of more targeted therapies - corticosteroid dosage can be reduced or eliminated completely in the future. Although corticosteroids have been the mainstay in the immunosuppressive treatment of patients who received a kidney transplant, there has been a long-standing interest in steroid avoidance and withdrawal (SAW). However, there is an ongoing debate whether SAW can be considered to be the standard of care in kidney transplantation at this moment.

Surgical Complications and Graft Survival in Pediatric Kidney Transplant Recipients Treated With a Steroid-Free Protocol: Experiences From a Danish University Hospital

BackgroundThe outcome of pediatric kidney transplantation depends on several factors, among these are the complications, which occur in relation to the surgical procedure. In this study, we present our experience with pediatric kidney transplantation in a steroid-free immunosuppression regimen, from a surgical point of view. MethodsPatient charts of pediatric kidney transplantations in the period 1998–2011 were reviewed. Surgical complications, acute rejection, and patient and graft survivals were recorded. ResultsSixty-one renal transplantations were performed in 58 patients. Thirty patients (49.1%) experienced a surgical complication, of which 11 (18%) required an explorative laparotomy. Overall the five-year Kaplan-Meier patient survival rate was 96.2% and the graft survival rate was 88.6%. Nine patients (14.7%) had an acute rejection episode within the first year after transplantation. No correlation was observed between surgical complications and acute rejection episodes or graft loss. ConclusionsThis study indicated a high incidence of surgical complications among pediatric kidney transplantations when using a steroid-free immunosuppression regimen. Despite this, we observed high overall patient and graft survival, supporting the trend toward steroids avoidance in pediatric kidney transplantation.

Longitudinal growth on an everolimus- versus an MMF-based steroid-free immunosuppressive regimen in paediatric renal transplant recipients

Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case-control study on longitudinal growth over 2 years in steroid-free pediatric renal transplant recipients. Fourteen patients on a steroid-free maintenance immunosuppressive regimen consisting of low-dose everolimus (EVR) in conjunction with low-dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid-free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch-up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid-free pediatric patients on low-dose EVR and CsA is not different to that of a matched steroid-free control group on an immunosuppressive regimen with standard-dose CNI and MMF. Hence, low-dose EVR does not appear to negatively impact short-term growth in pediatric renal transplant recipients.

Effect of steroid-free low concentration calcineurin inhibitor maintenance immunosuppression regimen on renal allograft histopathology and function

The most common cause of late kidney transplant failure is insidiously progressive renal dysfunction associated with organ scarring and fibrosis. Advanced donor age, delayed graft function, calcineurin toxicity and repeated acute rejection episodes are risk factors for this pathophysiology. We employed 3, 12 and 24 months surveillance renal biopsies, scored using the Chronic Allograft Damage Index (CADI), with periodic estimates of glomerular filtration rate (eGFR) to assess the effect of a steroid-free maintenance immunosuppression regimen on allograft histology and function. Ninety-one patients were induced with Alemtuzumab and then treated with mycophenolate sodium and low trough concentrations of tacrolimus. Fifty-six of 91 patients followed for 24 months showed no clinical rejection and in 16 more only minimal histological or borderline changes as defined by Banff criteria were observed. Histologically acute rejection was observed in 14 patients including two detected on surveillance biopsy. Five patients refused biopsies but showed stable eGFR for 24 months. Graft histopathology in the group with no rejection did not worsen. In contrast, nearly half the patients with acute rejection showed progression of CADI scores and a total of four grafts were lost over the 2 years. The 16 patients with borderline rejection changes exhibited stable glomerular filtration rate throughout, but 12.5% showed progression of CADI scores in the 12- to 24-month period. Following Alemtuzumab induction and in conjunction with low-dose tacrolimus and mycophenolate, continuous steroid therapy was not required to prevent progressive injury or preservation of graft function in patients without biopsy-proven acute rejection. Scored surveillance renal biopsies provide a useful tool to monitor transplanted kidneys.

Alterations of the Female Reproductive System in Islet Recipient Receiving Immunosuppression

Pancreatic islet allotransplantation is an option for patients with unstable type 1 diabetes mellitus (T1DM). Major improvements in islet isolation techniques and the implementation of steroid-free immunosuppressive regimens can maintain insulin independence in the majority of T1DM for at least 1 year after transplantation. Recent studies have emphasized the impact of sirolimus on female reproductive tract. In this communication we report on the alterations of the female reproductive tract in 18 chronically immunosuppressed patients with T1DM following allogenic islet transplantation. Previous research has shown development of ovarian cysts in islet transplant patients receiving sirolimus. We extensively reevaluated this and other possible side effects on the female reproductive system. These side effects have been underestimated, although they are significant, requiring surgical or intensive medical treatment. Pre- and posttransplant gynecological evaluation should be performed to address the development of complications secondary to sirolimus in order to intervene sooner with alternative therapies.

Steroid-free maintenance of islet allografts using mycophenolate mofetil and cyclosporine in the non-human primate

Islet transplantation continues to be a promising treatment for type 1 diabetes, however, numerous limitations still prevent its widespread use. Many immunosuppressive medications used for islet transplantation are known to be diabetogenic. The goal of this study is to evaluate the short-term follow-up (90 day) of a steroid-free maintenance immunosuppression protocol of mycophenolate mofetil (MMF) and cyclosporine (CSA) in non-human primate islet allotransplantation. Diabetes was induced in the primate Macaca fascicularis via total pancreatectomy. Freshly isolated islets were autotransplanted (n=5) or allotransplanted (n=5) into the portal vein. Immunosuppression consisted of induction with rabbit anti-thymocyte globulin (ATG) and prednisone. CSA (25 mg/daily) and MMF (250 mg daily) were used for maintenance and given orally once daily throughout the 90 day study period. Fasting blood glucose measurements were used to monitor graft function. Intravenous glucose tolerance tests (IVGTT) were performed prior to pancreatectomy and at the study endpoint. Average fasting blood glucose levels were elevated in diabetic controls (313.6 mg/dl ±51.8) and untreated allograft recipients (257 mg/dl ±61.0) post-transplant. Auto-transplanted animals and allograft recipients treated with immunosuppression, on the other hand, maintained normoglycemia (74.5 mg/dl ±20.9, 62.3 mg/dl ±4.40) throughout the follow-up period. Additionally, beta cell function and first phase insulin secretion did not differ significantly between auto-graft and immunosuppressed allo-graft recipients post-transplant. We conclude that this steroid-free maintenance immunosuppression regimen is effective in maintaining islet allograft survival in the non-human primate and offers comparable graft function to that of autografts for up to 3 months post-transplant.

Cost–benefit of steroid avoidance in renal transplant patients: A prospective randomized study

Steroids have played a major role in renal transplantation for more than four decades. However, chronic use of steroids is associated with a lot of comorbidities. This study aimed to assess the cost-benefit of steroid-free immunosuppression regimen in a prospective randomized controlled study of live donor renal transplantation, which was lacking in the literature. One-hundred patients were randomized to receive tacrolimus (Tac), mycophenolate mofetil (MMF), basiliximab (Simulect) induction and steroids only for 3 days (50 patients, study group) or Tac, MMF, Simulect induction and steroid maintenance (50 patients, control group). Median follow-up was 12 months. Both groups showed comparable graft and patient survival, rejection episodes and graft function. Post-transplant hypertension was detected in 4% of the steroid-free group and 24% of the steroid maintenance group (p = 0.0009), while post-transplant diabetes mellitus was detected in 4% and 16% of these two groups, respectively (p = 0.037). By the end of the first year, the cost of managing post-transplant morbidities was significantly higher in the steroid maintenance group, despite the comparable cost of immunosuppression. Among low immunological risk recipients of live donor renal transplants, steroid avoidance was feasible, safe and with less morbidity, using Simulect induction, and tacrolimus and MMF as maintenance immunosuppression. Steroid avoidance was associated with a lower total cost despite comparable immunosuppression cost, which was attributed to the lower cost of associated morbidities.

Results of Gal-Knockout Porcine Thymokidney Xenografts

Clinical transplantation for the treatment of end-stage organ disease is limited by a shortage of donor organs. Successful xenotransplantation could immediately overcome this limitation. The development of homozygous alpha1,3-galactosyltransferase knockout (GalT-KO) pigs removed hyperacute rejection as the major immunologic hurdle to xenotransplantation. Nevertheless, GalT-KO organs stimulate robust immunologic responses that are not prevented by immunosuppressive drugs. Murine studies show that recipient thymopoiesis in thymic xenografts induces xenotolerance. We transplanted life-supporting composite thymokidneys (composite thymus and kidneys) prepared in GalT-KO miniature swine to baboons in an attempt to induce tolerance in a preclinical xenotransplant model. Here, we report the results of seven xenogenic thymokidney transplants using a steroid-free immunosuppressive regimen that eliminated whole-body irradiation in all but one recipient. The regimen resulted in average recipient survival of over 50 days. This was associated with donor-specific unresponsiveness in vitro and early baboon thymopoiesis in the porcine thymus tissue of these grafts, suggesting the development of T-cell tolerance. The kidney grafts had no signs of cellular infiltration or deposition of IgG, and no grafts were lost due to rejection. These results show that xenogeneic thymus transplantation can support early primate thymopoiesis, which in turn may induce T-cell tolerance to solid organ xenografts.

Pancreatic islet transplantation

BackgroundNo formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR) from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects.ConclusionHuman islet transplantation should be regarded as an intervention that can decrease the frequency of severe hypoglycemic episodes and improve glycemic control in selected patient for whom benefits of 4-5 years duration would be very valuable. Its limitations, however, indicate that the procedure in its current format is not suitable for all patients with type 1 diabetes.

Prevalence and risk factors for delayed adrenal insufficiency after liver transplantation

Liver transplantation (LT) recipients are at risk for early and delayed adrenal insufficiency for multiple reasons. Although early adrenal insufficiency is known to occur in a high proportion of recipients maintained on steroid-free immunosuppressive regimens, the prevalence and risk factors associated with delayed functional adrenal gland atrophy (FAGA) are unknown because routine evaluation for this condition is not standard practice among LT centers. We investigated a group of 87 patients (64 males) transplanted for end-stage liver disease related to different etiologies. All underwent a standard corticotropin stimulation test (CST) when, after gradual steroid tapering, they had been maintained for at least 1 week on oral prednisone at a daily dose of 5 mg. FAGA, defined by a serum cortisol concentration that, 60 minutes after corticotropin administration, did not double the baseline level and remained <20 mug/dL, was diagnosed in 23/87 patients (26.4%). Stepwise logistic regression analysis selected as significant predictors of FAGA the cumulative dosage of corticosteroids administered (P < 0.01), the increase in the body mass index after LT (P < 0.01), a low serum cholesterol concentration (P = 0.005), and a high adrenocorticotropin hormone (ACTH) serum level (P < 0.05) at the time CST was performed. In conclusion, FAGA is a common condition among LT recipients who are maintained on prolonged corticosteroid immunosuppressive treatment. Factors associated with FAGA include the cumulative steroid dose, weight changes after LT, and ACTH and cholesterol levels at the time of steroid withdrawal.