Severity Of Acute Rejection Episodes Research Articles

Cardiac magnetic resonance imaging characterization of acute rejection in a porcine heterotopic heart transplantation model.

Preclinical disease models are important for the advancement of therapeutics towards human clinical trials. One of the difficult tasks of developing a well-characterized model is having a reliable modality with which to trend the progression of disease. Acute rejection is one of the most devastating complications that can occur following organ transplantation. Specifically in cardiac transplantation, approximately 12% of patients will experience at least one episode of moderate or severe acute rejection in the first year. Currently, the gold standard for monitoring rejection in the clinical setting is to perform serial endomyocardial biopsies for direct histological assessment. However, this is difficult to reproduce in a porcine model of acute rejection in cardiac transplantation where the heart is heterotopically transplanted in an abdominal position. Cardiac magnetic resonance imaging is arising as an alternative for serial screening for acute rejection in cardiac transplantation. This is an exploratory study to create and define a standardized cardiac magnetic resonance screening protocol for characterizing changes associated with the presence of acute rejection in this preclinical model of disease. Results demonstrate that increases in T1 mapping, T2 mapping, left ventricular mass, and in late gadolinium enhancement are significantly correlated with presence of acute rejection.

Conversion to belatacept after lung transplantation: Report of 10 cases.

Calcineurin inhibitors (CNIs) remain the cornerstone of maintenance immunosuppression (IS) after lung transplantation (LTx), although CNI-related life-threatening toxic effects may occur. Belatacept, a novel immunosuppressant that blocks a T-cell co-stimulation pathway, is a non-nephrotoxic drug indicated as an alternative to CNIs in kidney Tx. In LTx, there are only a few reports of belatacept conversion as a CNI-free or CNI-sparing IS treatment. We reviewed a series of 10 LTx recipients with conversion to a CNI-free belatacept IS regimen within the first year post-LTx (n = 7) or a belatacept/low-dose CNI combination after the first year (n = 3). Use of belatacept was triggered by severe renal failure in 9 patients and under-IS with previous other IS-related toxicities in 1 patient. Mean estimated glomerular filtration rate after starting belatacept significantly improved at 6 months after initiation and at the last-follow-up (p = 0.006, and p = 0.002 respectively). The incidence of recurrent and/or severe acute cellular rejection (ACR) episodes was high in patients with CNI-free belatacept-based IS (n = 4/7). Chronic graft allograft dysfunction developed in 2 of 9 recipients under belatacept IS. Belatacept was stopped in 6 patients because of recurrent/severe ACR (n = 3), recurrent opportunistic infections (n = 1), center modified policy (n = 1), or other cause (n = 1). Early conversion to CNI-free belatacept-based IS improved renal function in this series but was counterbalanced by a high incidence of recurrent ACR, including life-threatening episodes. Other studies are needed to better determine the indications for its use after LTx, possibly with lower immunological risk IS regimens, such as CNI-sparing belatacept.

Belatacept as salvage maintenance immunosuppression in a liver transplant recipient

Belatacept is a novel fusion protein that blocks signal two of T cell activation. Belatacept was approved in 2015 for the prevention of acute rejection in kidney transplant recipients. Results from a 2014 phase II clinical trial in liver transplant recipients was terminated early due to an increased risk of death and graft loss, leading to a black box warning for its use in liver transplant recipients. Here we describe the clinical course of a 55 year old male patient who underwent a liver transplant for cholestatic liver disease. His post-transplant course was complicated by multiple episodes of severe acute cellular rejection as well as multiple complications from maintenance immunosuppression including chronic kidney disease (CKD), steroid-induced diabetes, mycophenolate-associated colitis, and mammalian target of rapamycin (mTOR) inhibitor-induced lung injury. Belatacept was initiated 5 years post-transplant as a last-line option for maintenance immunosuppression. Six months post-initiation, the patient has had stabilization of his CKD, improvement in lung function, and remains without evidence of acute or chronic rejection.

3281 Management of Acute Rejection in Penile Allotransplantation

3281 Management of Acute Rejection in Penile Allotransplantation

Risk Factors and Expected Clinical Outcomes in Kidney Transplantation Based on 1 Year Serum Creatinine Levels

Background: This retrospective study delineates the variable risk factors associated with differences in renal function at 1 year post kidney transplantation. Materials and Methods:<b> </b>Two hundred and eighty four<b> </b>kidney transplant patients were reviewed and divided into 4 groups according to serum creatinine levels 1 year post kidney transplantation: serum creatinine levels < 1 mg/dl (Group I; 65 patients), serum creatinine between 1 and 1.51 mg/dl (Group II; 173 patients), serum creatinine between 1.51 and 2mg/dl (Group III; 37 patients) and serum creatinine > 2mg/dl (Group IV; 9 patients). Baseline demographics and variable risk factors in both donors and recipients were analyzed. Results:<b> </b>Baseline demographics of all groups were similar, including: recipient age, cause of the original kidney disease, dialysis duration, HLA matching, induction therapy, rate of acute rejection as well as the pre and 1 year post transplant diabetes, hypertension and lipid profile. However, there were significant differences between the groups according to: donor age, donor and recipient gender, maintenance immunosuppression therapy, recipient sensitization and the severity of acute rejection episodes. The rate and type of In Hospital infections, the duration of hospital stay, the occurrence of delayed graft function, the rate and type of surgical complications at 1 year as well as the serum creatinine levels upon discharge and at 1, 3 and 6 months were significantly different between the 4 groups. Conclusion:<b> </b>Serum creatinine level post-transplantation is a powerful predictor of long term graft survival. Although some risk factors associated with graft survival are fixed, others can be optimized.

Predictors of Long Term Survival in Visceral Transplant Recipients

Background: Despite continual improvement in early survival, the long-term outcomes of visceral transplantation remain conservative. Study Design: Single-center retrospective analysis of all visceral allograft recipients who underwent visceral transplant between November 2003 and December 2013 with at least 3 year follow up data. Clinical data from a prospectively maintained database was used to assess outcomes including patient and graft survival. Results: Of 174 recipients, 90 (51.7%) were adults and 84 (48.3%) were pediatric patients. Types of visceral transplants were 98 (56.3%) isolated intestinal transplant, 44 (25.3%) combined liver intestinal transplant, and 32 (18.4%) multi-visceral transplant. Median follow up was 8.1 (3–13.2) years. 3-, 5-, and 10-year overall patient survival was 69.5%, 66%, and 63%, respectively, while 3-, 5-, and 10-year overall graft survival was 67%, 62%, and 61%, respectively. In univariable analysis, significant predictors of survival included pediatric recipient (odds ratio [OR] = 2.138; 95% CI, 1.251-3.656); P= 0.005), low donor/recipient weight ratio (odds ratio [OR] = 1.224; 95% CI, 1.017-1.473; P= 0.032), no episodes of severe acute rejection (odds ratio [OR] = 1.939; 95% CI, 1.160-3.243; P= 0.012), history of functional bowel problem (odds ratio [OR] = 1.950; 95% CI, 1.142-3.332; P= 0.014), no simultaneous kidney transplantation (odds ratio [OR] = 3.138; 95% CI, 1.250-7.880; P= 0.015) and less HLA-A mismatch (odds ratio [OR] = 1.815; 95% CI, 1.098-3.012; P= 0.02). In multivariable analysis, significant predictors of survival included pediatric recipient (odds ratio [OR] = 2.249; 95% CI, 1.256-4.027); P= 0.006), low donor/recipient weight ratio (odds ratio [OR] = 1.234; 95% CI, 1.023-1.488; P= 0.028) and no episodes of severe acute rejection (odds ratio [OR] = 2.032; 95% CI, 1.158-3.566; P= 0.013). Conclusions: Visceral transplantation remains a good option for treatment of end stage intestinal failure with parenteral nutritional complications. Proper graft selection and improvement of immunosuppression regimens could significantly improve the long-term survival.

Intestine Transplantation Across a Positive Crossmatch With Preformed Donor-Specific Antibodies

BackgroundWe describe our experience using a modified protocol for immunosuppression for intestine transplantation across a positive crossmatch. Patients who underwent transplantation in 2013 were evaluated over a 12-month period for rejection and infectious events with comparison to procedure-matched controls on our standard protocol of immunosuppression. Patients and MethodsWe used a modified protocol for intestine and multivisceral transplantation for patients with a positive flow crossmatch. In addition to our standard protocol, patients with positive crossmatch were given rituximab and intravenous immunoglobulin (IVIg) preoperatively. DSA was sent for clinical evaluation at monthly intervals. Patients were screened for rejection by endoscopic evaluation. ResultsFour patients underwent transplantation within a single year across a positive crossmatch. Two received isolated intestine transplants and 2 had multivisceral transplantation (MVT). During the 12-month follow-up, 1 patients had an episode of severe acute cellular rejection, which was managed with increased immunosuppression. None of the patients had episodes of cytomegalovirus infection. One patient developed major infection and 3 patients developed minor bacterial infections. Among procedure-matched controls with negative final crossmatch on standard management (no preoperative rituximab or IVIg), 2 developed mild acute cellular rejection and 2 developed minor infections. One developed cytomegalovirus viremia with invasion to the colonic mucosa. ConclusionsWe report our protocol for immunosuppression for IT and MVT across a positive crossmatch. This allowed transplantation despite the presence of a positive crossmatch, with low rejection rates but potentially increased risk for major infections compared to the negative crossmatch controls on our standard protocol.

Monitoring B cell subsets and alloreactivity in kidney transplantation.

B cells are the precursors of antibody producing plasma cells that can give rise to the formation of donor-specific antibodies. However, recent data suggest that besides their role in antibody production, B cells participate in antibody-independent responses, potentially leading to allograft rejection or allograft tolerance. The presence of CD20(+) B cells in kidney graft biopsies has been shown during severe acute rejection episodes and during chronic rejection. Furthermore, operationally tolerant kidney transplant recipients showed a clear B cell dominated fingerprint of tolerance. Several techniques exist to study B cells on different levels. Numerous classification schemes allow for the distinction of many different B cell subsets using flow cytometry. Regardless, data on B cell subsets during stable graft function, rejection or tolerance remain scarce. To obtain a complete picture of the role of B cells during transplantation, antigen specific B cell assays may be required. Therefore, techniques have now been developed that allow for studying the specificity and frequency of HLA specific B cells. Here, we present an overview of the existent assays, panels and techniques intended to characterize peripheral B cells, and the currently available HLA specific B cell functional assays that may allow for monitoring the humoral alloimmune response in transplant recipients.

New immunosuppressants in pediatric solid organ transplantation

This review examines new developments in the prophylaxis and treatment of rejection episodes as there has been a marked improvement in patient and allograft survival in pediatric solid organ transplant recipients over the last 20 years. Improved surgical techniques to allow transplantation of smaller recipients and a wider range of immunosuppressants available to transplant physicians have improved access and reduced the incidence and severity of acute rejection episodes and chronic allograft damage. There is increasing knowledge of chronic allograft damage and the role of humorally-mediated rejection, leading to better understanding of the mechanisms involved and potential treatments. There is evidence in the literature of potential targets of B-cell survival factors by inhibiting novel pathways involved in B-cell and plasma cell activation. There are currently trials underway investigating the use of eculizumab and bortezomib for treatment of antibody-mediated rejection as well as utilising these agents as part of desensitisation protocols. Minimal (or even monotherapy) maintenance immunosuppression regimens include monoclonal antibodies and fusion receptor proteins targeting different pathways (CD40-CD154, CD28-CD80/86, and LFA3-CD2 pathway). Phase III randomised controlled trials in adults are required before embarking on treatment of children.

Significance of Mycophenolate Monitoring in Liver Transplant Recipients: Toward the Cut-off Level

Mycophenolate mofetil blocks the “de novo” -purine synthesis to reduce the incidence and severity of acute rejection episodes. There has been an increased interest in utility of monitoring mycophenolic acid (MPA) levels, however currently the MPA monitoring is not part of the protocol following liver transplantation. We assessed whether trough MPA monitoring could be advisable in liver transplant patients or not. For this reason MPA levels of 56 liver transplants were measured on 3, 5, 10, 14, 21, 30, 60, and 180 posttransplant days. The optimal cut-off of MPA level (≥1.73 mg/L) for all (56) and ≥1.34 mg/L for ciclosporin-treated- and ≥1.98 mg/L for the tacrolimus-treated transplants were calculated by statistical analysis to reduce the incidence of acute rejection. MPA concentrations of 3 days period before the day of clinical diagnosis acute rejection were well below the cut-off value. Only 3 (16%) out 19 patients with acute rejection had higher MPA levels than the cut-off value on the day of diagnosis of acute rejection. In conclusion, our data suggests that MPA predose level monitoring, especially in the early “filling phase” after transplantation, is applicable in liver allograft recipients given adjunctive MMF, protecting them from the ineffective immunosuppression.

Donor lung derived myeloid and plasmacytoid dendritic cells differentially regulate T cell proliferation and cytokine production

BackgroundDirect allorecognition, i.e., donor lung-derived dendritic cells (DCs) stimulating recipient-derived T lymphocytes, is believed to be the key mechanism of lung allograft rejection. Myeloid (cDCs) and plasmacytoid (pDCs) are believed to have differential effects on T cell activation. However, the roles of each DC type on T cell activation and rejection pathology post lung transplantation are unknown.MethodsUsing transgenic mice and antibody depletion techniques, either or both cell types were depleted in lungs of donor BALB/c mice (H-2d) prior to transplanting into C57BL/6 mice (H-2b), followed by an assessment of rejection pathology, and pDC or cDC-induced proliferation and cytokine production in C57BL/6-derived mediastinal lymph node T cells (CD3+).ResultsDepleting either DC type had modest effect on rejection pathology and T cell proliferation. In contrast, T cells from mice that received grafts depleted of both DCs did not proliferate and this was associated with significantly reduced acute rejection scores compared to all other groups. cDCs were potent inducers of IFNγ, whereas both cDCs and pDCs induced IL-10. Both cell types had variable effects on IL-17A production.ConclusionCollectively, the data show that direct allorecognition by donor lung pDCs and cDCs have differential effects on T cell proliferation and cytokine production. Depletion of both donor lung cDC and pDC could prevent the severity of acute rejection episodes.

Soluble Human Leukocyte Antigen-G in Pediatric Renal Transplantation

Soluble Human Leukocyte Antigen-G in Pediatric Renal Transplantation

Azithromycin and bronchiolitis obliterans syndrome after lung transplantation: is prevention better than cure?

Although lung transplantation is now accepted as an established therapy for selected patients with end-stage lung disease, long-term survival after lung transplantation remains limited by the development of bronchiolitis obliterans syndrome (BOS) in >50% of recipients 1. BOS is the clinical manifestation of an inflammatory bronchiolitis associated with fibrotic remodelling of the small and medium-sized airways, and is characterised by progressive loss of allograft function with development of airflow obstruction 2, 3. Until recently, the development of BOS was associated with an irreversible and relentless decline in lung function, which either eventually stabilised at a very low level or, in many patients, progressed to end-stage respiratory failure, accounting for the commonest cause of death after the first post-transplant year. BOS has historically been attributed to the effects of ongoing alloimmune injury as both the frequency and severity of acute rejection episodes have been associated with increased risk 4. These observations lead to the paradigm that BOS is chronic rejection of the transplanted lung and, consequently, intensification of immunosuppression was used as an attempted therapy in many affected recipients. These approaches offered, at best, a slowing in the progression of the condition in some, but also contributed to infective complications that undoubtedly added to the overall mortality risk from BOS. Over the last decade, a number of clinical trials of more intensive immunosuppressive regimes from the time of transplant or after onset of BOS have failed to impact on the incidence of BOS or regaining of lost function 5, 6. More recently, however, it has been appreciated that nonalloimmune insults to the lung allograft, such as the lung injury of primary graft dysfunction, viral and bacterial infections, and aspiration injury, also increase the risk of developing BOS 7. This suggests that cross-talk between innate …

Evaluation of Calprotectin Level in Intestinal Content as an Early Marker for Graft Rejection

Introduction The diagnosis of rejection after intestinal transplantation is still performed by endoscopic biopsy monitoring. Less invasive diagnostic procedures are desirable, although they are not available so far. Calprotectin, a stable cytosolic granulocyte protein, which previously was used as a marker of inflammatory processes, has been proposed to be a biochemical marker for rejection. The aim of the present work was to analyze the concordance between calprotectin levels in intestinal content and the presence of graft rejection after small bowel transplantation. Methods Calprotectin level was measured using a commercial ELISA kit on 137 samples of intestinal content randomly collected during endoscopies performed on 11 intestinal transplantation patients during 2 years' follow-up. Calprotectin determinations were correlated with histological and clinical findings. The cut-off level was determined retrospectively by receiver-operator curve analysis. Results Based on histological findings and clinical records, samples were discerned as rejection positive (37 of 137), versus negative (35 of 137) samples or those with no clinical, endoscopic, or histological findings (65 of 137 samples). A cut-off value of 65 μg of calprotectin/g of intestinal content provided the best assay parameter according to the clinical findings: a 76% sensitivity and a 47% specificity. False positive results corresponded to patients with gastrointestinal infections (13%), systemic infections (13%), ulcers (10%), or nonspecific histological alterations of the mucosa (15%). The other false positive cases corresponded to postsurgical samples (4%), or patients with concomitant gastrointestinal symptoms (2%). Most false negative results (78%) were observed during recovery from severe acute rejection episodes, among successfully treated patients. In these cases, epithelial reconstitution and no mucosal infiltration was observed. If the latter group were discarded, sensitivity rose to 93%, and specificity, to 50% with a 96% negative predictive value. Furthermore, a weak correlation was observed between calprotectin levels and the severity of rejection. Conclusions This study confirmed the results obtained by other groups: fecal calprotectin dosage showed a good sensitivity but low specificity for the diagnosis of intestinal rejection because high calprotectin levels can also be observed in other clinical conditions. Nevertheless, it might be used as a first line for continuous evaluation of intestinal transplantation status, like other biochemical parameters that are used in kidney or liver transplantation, before considering the need for a biopsy.

Results of Heart Transplantation: 16 Years' Experience in a Center in Argentina

Heart transplantation (HTx) is the treatment of choice for advanced heart failure refractory to other treatments. Objective To report the outcomes of patients undergoing orthotopic HTx in a center with 16 years' experience. Methods We retrospectively examined the outcomes from three hundred nine HTx recipients between February 1993 and March 2009. The mean recipient age was 46 ± 16 years, and 80% were male. Ischemic cardiomyopathy was present in 37%; 43% (n = 133) were elective procedures and 57% (n = 176) were urgent/emergency procedures. The mean donor age was 26 years; their main cause of death was head/brain trauma. Survival was studied using Kaplan-Meier curves. Results The global survival rates at 1, 5, 10, and 15 years were 80%, 74%, 71%, and 65%, respectively. Excluding losses during the first year after transplantation (conditional survival), the survival rate at 5 and 10 years reached 92% and 88.5%, respectively. The median follow-up was 7.7 years. The etiology and the urgent/emergency nature of the procedures did not show significant differences regarding the mortality rate ( P = .8). The main causes of death were sepsis (28%) and primary nonfunction (18%). In-hospital mortality reached 16%. No significant differences were observed between the urgent/emergency versus the elective transplant procedures ( P = .06). During the follow-up, the incidence of severe acute cellular rejection episodes was <3% after 5 years. The global incidence of antibody-mediated rejection reached 4.5%. Eleven subjects (3.5%) were diagnosed with post-transplantation lymphoproliferative disorder. During long-term follow-up, the incidences of kidney failure, diabetes mellitus, hypertension, and dyslipemia were 21%, 24%, 69%, and 70%, respectively. One percent required chronic dialysis. Conclusion In our center, post-HTx survival rates at 1, 5, 10, and 15 years were 80%, 74%, 71%, and 65%, respectively, which were similar to those reported by the International Society of Heart and Lung Transplantation (ISHLT).

Estimated Glomerular Filtration Rate Evolution Between 6 and 24 Months Predicts Long-Term Kidney Transplant Survival Among Patients With Inferior Graft Function

One-year serum creatinine and other clinical and immunologic factors remain uncertain predictors of long-term kidney allograft outcomes. The aim of our retrospective study was to evaluate the prognostic significance of the estimated glomerular filtration rate (eGFR) monitoring of patients with suboptimal kidney allograft function. The analysis included 332 patients (median age, 43 years), who received deceased donor kidney transplantations between 1995 and 2007 with graft function for at least 1.5 years (median follow-up, 7 years). We examined the eGFR (the 4-variable Modification of Diets in Renal Disease [MDRD] equation) at 6 month posttranspant and every 6 months thereafter. Based on eGFR stratification (>60, 50–60, 40–49, and <40 mL/min per 1.73 m 2) at 6 months we divided the patients into 4 groups. We identified patients with eGFR improvement (as judged by >20% increment between 6 and 24 months), versus stable or declining eGFR courses. Results Among the groups, the eGFR improved among 47% of patients. Demographic characteristics including time on dialysis, human leukocyte antigen matching, cold ischemia times were similar across groups. A greater incidence of disadvantageous characteristics was observed among the deteriorating groups: older donor, higher delayed graft function incidence, as well as more frequent and severe acute rejection episodes. Excellent and comparable 5-year graft survivals were noticed among patients with improved eGFR between 6 and 24 months (97%, 100%, 100%, 94%). Conclusion Assessment of eGFR was a valuable biomarker for long-term kidney transplant outcomes among patients with inferior renal transplant function. A tendency to improve eGFR between 6 and 24 months posttransplant was advantageous for graft survival, possibly indicating state of immunologic quiescence.

Minimization of Maintenance Immunosuppression Early After Renal Transplantation: An Interim Analysis

Chronic allograft nephropathy is the main cause of long-term renal transplant failure. Chronic use of calcineurin inhibitors contributes to its pathogenesis. Here, we report on a multicenter randomized trial to study the effects of withdrawal of cyclosporine A (CsA) from a triple immunosuppressive regimen containing CsA, prednisolone (P), and mycophenolate sodium (MPS) early after transplantation. Patients continued on P/CsA, P/MPS, or P and everolimus (EVL). Before withdrawal, a transplant biopsy was performed ensuring no subclinical rejection was present. Drug levels were closely monitored. The primary outcome was interstitial graft fibrosis and hyalinosis. Secondary outcome was among others graft rejection. According to trial regulations, an interim analysis was performed after enrollment of half of the intended number of patients (n=113). Mean follow-up was 14+/-5 months from transplantation and 8+/-5 months from conversion. After conversion, acute rejection percentages were 3% in the P/CsA group, 22% in the P/MPS group, and 0% in the P/EVL group (P<0.009). We conclude that switching immunosuppressive therapy from P/CsA/MPS to therapy with P/CsA or P/EVL at 6 months after renal transplantation is effective in preventing rejection. Double therapy with P/MPS after withdrawal of P/CsA resulted in an increase in severe acute rejection episodes. These results were the immediate reason to halt the P/MPS arm. Serum creatinine values at the latest follow-up (8+/-5 months after conversion and 14+/-5 months after transplantation) in the P/EVL group were lower than in the P/CsA group.

Clinical Application of Cordyceps sinensis on Immunosuppressive Therapy in Renal Transplantation

Objective We sought to explore the adjunctive effects of Cordyceps sinensis (CS) in clinical renal transplantation. Materials and Methods Patients (n = 202) were divided randomly by lottery into a treatment (n = 93) and a control group (n = 109). Patients in the treatment group were treated with CS 1.0 g 3 times a day in addition to the immunosuppressive regimen given to the control group. We compared patient and graft survivals, incidence, time and severity of acute rejection episodes, chronic allograft nephropathy (CAN), hepatotoxicity and nephrotoxicity, biochemistry parameters including indicators of liver and kidney functions, fats, proteinuria, dosages, and whole blood concentrations of cyclosporine (CsA). Results Patient and graft survival rates, serum creatinine (SCr), and blood urea nitrogen (BUN) were not significantly different between the 2 groups ( P > .05). Serum uric acid (UA) and 24-hour urinary total protein (24-hour UTP) were significantly lower in the treatment group than in the control group ( P < .05). The incidences (11.83% vs 15.60%) and times to acute renal allograft rejection (23.48 ± 7.22 vs 22.27 ± 8.03 days posttransplantation) were not significantly different between the treated and control groups ( P > .05). Patients receiving thymoglobulin antirejection therapy (3 cases) were fewer in the heated versus control group (13 cases; P = .014). The incidences of hepatotoxicity and nephrotoxicity in the treated group were 12.90% and 19.35%, significantly lower than 24.77% and 33.94% in the control group, respectively ( P < .05). At 2 to 6 months posttransplantation, the CsA dosages in the treated group were significantly lower than those in the control group ( P < .05). The whole blood trough CsA concentrations in the treated group were significantly lower than those in the control group at 3 to 6 months posttransplantation ( P < .05). The decreasing trends of the 2 aforementioned parameters in the treatment group were approximately linear among treated subjects compared with approximately quadratic in the control group ( P < .05). The incidence of CAN in the treated group was 7.53%, which was significantly lower than 18.35% in the control group ( P = .024). The 24-hour UTP level in CAN patients within the treated group was significantly lower than the control group after transplantation ( P = .045). The differences in total bilirubin, SCr, serum UA, and total cholesterol levels among otherwise normal patients in the treated group were significantly lower than those among the control group ( P < .05). Conclusions The use of CS may allow decreased dosages and concentrations of CsA causing fewer side effects without an increased risk of acute rejection. In addition, CS with reduced dose CsA may decrease proteinuria and retard CAN progression.

Mycophenolate mofetil: safety and efficacy in the prophylaxis of acute kidney transplantation rejection

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is an inhibitor of inosine monophosphate dehydrogenase (IMPDH). It preferentially inhibits denovo pathway of guanosine nucleotide synthesis in T and B-lymphocytes and prevents their proliferation, thereby suppresses both cell mediated and humoral immune responses. Clinical trials in kidney transplant recipients have shown the efficacy of MMF in reducing the incidence and severity of acute rejection episodes. It also improves long term graft function as well as graft and patient survival in kidney transplant recipients. MMF is useful as a component of toxicity sparing regimens to reduce or avoid exposure of steroids or calcineurin inhibitor (CNI). Enteric-coated mycophenolate sodium (EC-MPS) can be used as an alternative immunosuppressive agent in kidney transplant recipients with efficacy and safety profile similar to MMF.

Conversion to Sirolimus in Kidney–Pancreas and Pancreas Transplantation

Reports on the use of sirolimus (SRL) in pancreas transplantation are still limited. The aim of this study was to evaluate the outcome of SRL conversion in pancreas transplant patients. Among 247 patients undergoing simultaneous kidney-pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL. The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity ( n = 24; 73%), severe neurotoxicity owing to CNI ( n = 1; 3%), severe and/or recurrent acute rejection episodes ( n = 7; 21%), gastrointestinal (GI) side effects of mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia ( n = 4; 12%). Before conversion, all patients were maintained on a CNI, MMF, and low-dose steroids. They were gradually converted to SRL associated with either CNI or MMF withdrawal. Sixty-three percent ( n = 15) of patients who were converted owing to CNI nephrotoxicity, showed stable or improved renal function. At 12 months after conversion, serum creatinine levels were significantly decreased in this group (2.2 ± 0.5 vs 1.6 ± 0.3 mg/dL; P = .001) and C-peptide values increased (2.9 ± 1.1.1 vs 3.1 ± 1.3 nmol/L; P = .018). The only patient with leucoencephalopathy showed improved neurologic status after SRL conversion. All patients converted to SRL because of GI side effects of MMF showed improvements, and none of those converted because of hyperglycemia experienced improvement. There were no episodes of acute rejection after conversion. We concluded that conversion to SRL in pancreas transplantation should be considered an important alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and in cases of severe diarrhea due to MMF.