First Month Of Transplantation Research Articles

Risk factors for early onset acute kidney injury after allogeneic haematopoietic stem cell transplantation and the role of drug–drug interactions

IntroductionAcute kidney injury (AKI) is an important and life-threatening complication following allogeneic haematopoietic stem cell transplantation (allo-HSCT). This is therefore an active research area with studies aiming to understand the...

Is diagnostic stewardship possible in solid organ transplantation?

Diagnostic stewardship in solid organ transplant (SOT) recipients has the potential to help these vulnerable patients at risk for over-testing and overtreatment. Herein, we review potential targets for diagnostic stewardship in SOT, such as Clostridioides difficile testing, urine cultures, molecular diagnostics, as well as novel areas of diagnostic stewardship. Bundled interventions focused on appropriate C. difficile testing can result in a significant decrease in testing and clinical diagnosis of C. difficile infection without any harms related to delay in diagnosis. In otherwise stable renal transplant recipients after the first month of transplant, screening urine cultures have not been shown to improve outcomes. Novel targets that require additional study in the SOT population include noninvasive fungal diagnostics and cytomegalovirus testing strategies CONCLUSIONS: Diagnostic stewardship is an innovative approach to improve diagnosis and limit unnecessary antimicrobial use. While there has been little direct exploration of diagnostic stewardship in the SOT population, there is great potential for benefit given frequent testing with diagnostics that have imperfect sensitivity and specificity, and sometimes great cost. Diagnostic stewardship in the SOT population is indeed possible but will require a multidisciplinary effort to ensure that appropriates tests and benefits are realized.

P1644SAPS AND EPTS SCORES AS PREDICTORS OF RENAL FUNCTION IN RECENT RENAL TRANSPLANTATION

Abstract Background and Aims The risk scores used in Critical Care Units estimate the severity and mortality of patients. The SAPS (Simplified Acute Physiologic Score) and its SAPS II and SAPS III variants calculate the severity by collecting the values recorded in the first 24 hours. The EPTS (Estimated Post-Transplant-Survival) is used as a reference for the allocation of organs in the US by the OPTN. The objective is to determine its use in recent renal transplant units as estimator of subsequent renal function, in services where patients move from the operating room to a nephrological intermediate care unit. Method The SAPS (II and III) and OPTN scores were applied in 87 (N = 87) consecutive renal transplanted patients. The point value of each of the scales was evaluated with the creatinine values at hospital discharge, and one month after the transplant. The scores obtained on the SAPS scales were divided as follows (SAPSIIA <20 points, SAPSIIB ≥20 points) (SAPSIII A <30 points, SAPSIIIB ≥30 points). In the EPTS scale, two cut-off points were used to divide the groups (20% Score; EPTS-IA ≤20%, EPTS-IB> 20%), (Score 40%; EPTS-IIA ≤40%, EPTS -IIB> 40). The sérum creatinine means of each of the groups were compared. Data were analyzed with SPSS 20.0.0 Results Significant differences were found in serum creatinine levels in renal function at the first month of transplantation in the SAPS II groups (SAPS IIA 1.38 mg / dl, SAPS IIB 1.79 mg / dl; P = 0.017 95% CI). With an area under the ROC curve of 0.65 (P = 0.017 95% CI). In the SAPS III groups no significant differences were found. In the EPTS scales, there were also significant differences in creatinine one month after the transplant in the group with a score of 40% (EPTS-IIA ≤40% 1.42 mg / dl, EPTS-IIB> 40 1.81 mg / dl; P = 0.024 95% CI) With an Area under the ROC curve of 0.64 (P = 0.037 95% CI). Conclusion The SAPSII and EPTS scores can be a useful tool in estimating renal function one month after renal transplantation, giving a prognosis of renal graft function. The combined use of these scales together with other functional graft tests could have an important relevance in the management and follow-up of recent renal transplantation. Other studies with larger sample sizes are necessary to establish the appropriate cut-off points for the scales.

Identification of Antibiotic Administration as a Potentially Novel Factor Associated With Tacrolimus Trough Variability in Kidney Transplant Recipients: A Preliminary Study.

We conducted a retrospective chart review of subjects who received kidney transplants at our institution from 2012 to 2013 and evaluated subjects who received antibiotics during the first month of transplantation (Abx Group, N = 60) and subjects who did not (No Abx Group, N = 200). We evaluated whether antibiotic administration in the Abx Group had increased tacrolimus trough concentrations and concentration over tacrolimus dosage (C/D) after antibiotic administration. We also evaluated tacrolimus variability as measured by standard deviation (SD) and coefficient of variation between the Abx Group and No Abx Group. In the Abx Group, tacrolimus trough concentration over tacrolimus dosage (C/D) increased 7 and 15 days after antibiotic administration (P = 0.001, P = 0.07, respectively, Wilcoxon signed-rank test). From postoperative day 31-45, the variability in tacrolimus trough levels in the Abx Group as measured by SD and coefficient of variation was significantly higher than the variability in the No Abx Group (P = 0.03, P = 0.02, Wilcoxon rank sum test, respectively). Our identification of antibiotic administration as a potentially new risk factor for tacrolimus trough variability suggests the need to carefully follow tacrolimus trough levels after antibiotic administration.

Vitamin D supplementation could reduce the risk of acute cellular rejection and infection in vitamin D deficient liver allograft recipients

BackgroundVitamin D regulates the immune system and affects the outcome of allografts. We investigated the mechanisms underlying the preventative potential of vitamin D in acute cellular rejection (ACR) and infection, and determined its effects on the induction of both T cells and complement. MethodsA total of 141 patients who received a liver allograft at our center between 2012 and 2016 were enrolled in the study and divided into a vitamin D supplementation group (case group, n = 71) and a non-vitamin D supplementation group (control group, n = 70). Serum was collected in the hours prior to transplantation and within the first month of transplantation. We evaluated the relationship between the serum levels of 25-hydroxyvitamin D ACR, infection, T cells, complement, and graft function. Follow-up was conducted until patient death or June 30, 2018. ResultsVitamin D deficiency was an important independent risk factor for ACR. The incidence of ACR, and bacterial and fungal infection was reduced in patients with vitamin D supplementation. The frequency of Treg, Tmemory, T naïve cells and CD8 + CD28+ T cells (CTL) and the level of complement component 3 were related to ACR in the first month after transplantation. This study showed increased numbers of Treg cells and Tmemory cells and decreased numbers of Naïve cells and CTL in the case group. Vitamin D status was significantly associated with mortality. ConclusionsVitamin D supplementation is associated with a lower risk of ACR and infection, suggesting that it may promote immune tolerance towards the liver allografts.

Urinary C‑X‑C motif chemokine 13 is a noninvasive biomarker of antibody‑mediated renal allograft rejection.

Noninvasive monitoring methods of immune status are preferred by transplant recipients. The present study investigated whether urinary C‑X‑C motif chemokine 13 (CXCL13) had the potential to reflect ongoing immune processes within renal allografts. Using an ELISA assay, the level of urinary CXCL13 was quantified in a total of 146 renal allograft recipients and 40healthy controls at scheduled intervals and at the time of the indicated or protocol biopsy. The results of the present study revealed that urinary CXCL13/creatinine (Cr) was lower in normal transplants compared with in those with acute tubular necrosis (ATN; P=0.001), chronic allograft nephropathy (CAN; P=0.01), and acute rejection (AR; P<0.0001), which was associated with a good diagnostic performance for AR [area under the curve (AUC)=0.818, P<0.0001). In addition, urinary CXCL13/Cr levels in patients with AR were also higher than that of patients with graft dysfunction but no rejection, including ATN and CAN (P=0.034). Notably, urinary CXCL13 distinguished between acute antibody‑mediated rejection (ABMR) and acute cellular rejection, with an AUC of 0.856. Furthermore, patients with steroid‑resistant AR exhibited significantly increased urinary CXCL13/Cr levels than patients with reversible AR (P=0.001). Additionally, elevated levels of urinary CXCL13/Cr within the first month of transplant were predictive of graft function at 3 and 6months (P=0.044 and P=0.04, respectively). Collectively, the findings of the present study indicated that the noninvasive investigation of urinary CXCL13/Cr may be valuable for the detection of AR, particularly ABMR. In addition, high urinary CXCL13/Cr levels predicted a poor response to steroid treatment and compromised graft function.

Profile of Anemia in pediatric liver transplant recipients

Objection: To investigate the frequency, etiology and clinical significance of anemia in pediatric liver transplant recipients according to the pre-transplant and post-transplant file records. Material and Method: The study included 81 of 97 children with complete file records who underwent liver transplantation between May 2000 and February 2011 at the Istanbul University Istanbul School of Medicine Departments of Hepatobiliary Surgery and Pediatric Hepatology. We recorded hemoglobin values before and at 1st day, 1st week and 1st month after transplantation. Results: Majority of the transplanted children were males 67.9% and transplant recipients from living donors 76.5% . The median age of the patients was 54 months and most common indications of transplantation were cholestatic liver diseases 37% , metabolic liver disease 19.7% and cryptogenic cirrhosis 13.5% mostly with signs of hypersplenism. Anemia was detected before transplantation n=50, 61.7% , first day n=63, 77.8% , first week n=51, 63.0% and first month n=41, 50.6% of transplantation. The mean Hb values before 10.0±1.4 g/dL , and first day 9.42±1.32 g/dL , first week 9.75±1.20 g/dL , and first month 10.2±1.56 g/dL of transplantation. The Hb change between pre- and post-transplant periods was significant. Splenomegaly was detected in 36 of 50 cases with anemia before transplantation. A significant difference was detected between splenomegaly and anemia before transplantation. Splenomegaly was detected in 19 of 41 cases with anemia in the first month of post-transplant. Conclusion: The frequency of anemia has increased during early period of transplantation 77.8% in first day while its incidence significantly decreased by 50.6% in the first month of transplantation due to ameliorating hypersplenism. In addition, splenomegaly that has determinant role in frequency of anemia during pre-transplant period had lost its significance after transplantation.

The impact of flow PRA on outcome in pediatric heart recipients in modern era: An analysis of the Pediatric Heart Transplant Study database.

Data from patients in the Pediatric Heart Transplant Study (PHTS) registry transplanted between 2010 and 2014 were analyzed to determine the association between HLA antibody (PRA) determined by SPA using Luminex or flow cytometry with a positive retrospective cross-match and the post-transplant outcomes of acute rejection and graft survival. A total of 1459 of 1596 (91%) recipients had a PRA reported pretransplant; 26% had a PRA>20%. Patients with a PRA>20% were more likely to have CHD, prior cardiac surgery, ECMO support at listing, and waited longer for transplantation than patients with a PRA <20%. Patients with higher PRA% determined by SPA were predictive of a positive retrospective cross-match determined by flow cytometric method (P<.001). A PRA>50% determined by SPA was independently associated with worse overall graft survival after first month of transplant in both unadjusted and adjusted for all other risk factors. In this large multicenter series of pediatric heart transplant recipients, an elevated PRA determined by SPA remains a significant risk factor in the modern era.

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OBJECTIVES/SPECIFIC AIMS: Aim 1: To compare microbiome diversity among patients who develop BSI post hematopoietic stem cell transplantation (HSCT) and patients without BSI. Aim 2: To compare microbiome diversity among patients who develop moderate to severe acute GVHD post HSCT and patients without GVHD. Aim 3: To describe alterations in specific bacterial orders (Enterobacteriaceae, Clostridia, and Lactobacillales) in pediatric patients undergoing HSCT. METHODS/STUDY POPULATION: Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from stool specimens collected at baseline (start of preparative regimen to transplant day), early (day 7–14 post HSCT), and late (day 21–28 post HSCT) from 46 children was performed. Microbiome diversity was assessed by the Shannon index as well as UniFrac analysis, and compared among patients with and without GVHD/BSI. Baseline bacterial diversity was compared among patients by primary diagnosis, race, timing of antibiotic introduction and method of supplemental nutrition. RESULTS/ANTICIPATED RESULTS: Median age was 9 years (range 0.5–19.2 years). There were 36 patients with hematologic malignancies. Patients with nonmalignant disease had a characteristic pattern of microbiome diversity (and microbiota order distribution) at baseline that persisted throughout the first month of transplant (p=0.004). Over all patients, there was an early and persistent drop in microbiome diversity throughout the transplant course. Early introduction of broad spectrum antibiotics (prior to transplant day) negatively impacted microbiome diversity (p=0.02). There was no difference in microbiome diversity among patients who developed BSI, when compared with patients without BSI. Similarly, we did not find an association between microbiome diversity and the development of moderate to severe acute GVHD. Ongoing analysis is examining the individual variations in microbiome at the species level, and their relation to transplant characteristics and clinical outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: In our analysis, microbiome diversity decreased during HSCT, but in contrast to published data, mainly in adult HSCT populations, we found no association between gut microbiome diversity and GVHD or BSI. There are ongoing clinical trials in children and adults using probiotics in HSCT with the aim of decreasing GVHD. Further analysis of our data at the species level may further inform the relationship between gut microbiome alterations and HSCT complications in children and guide clinical interventions.

342 - Predictors and Characteristics of Pericardial Effusions Post OHT

Introduction: The predictors and features of pericardial effusions post OHT are unclear. Prior investigations have identified size mismatch between donor and recipient, rejection, and prior sternotomy as factors that predict the development of pericardial effusions. Hypothesis: The aim of this study was to assess risk factors for the development of post OHT pericardial effusions, describe their etiology, location and methods of treatment or follow up. Methods: The records and echocardiograms of all patients receiving heart transplants at a large academic medical center between 4/2007-4/2015 were reviewed for the presence of pericardial effusion in the first year post OHT. Effusions were characterized by size (small, moderate, large), location (anterior, posterior, circumferential) and need for intervention. Baseline characteristics were investigated as potential predictors of effusion development via logistic regression. Results: Of the 214 patients receiving heart transplants, 77 (36%) had effusions within the first year. The only predictor for the development of pericardial effusion was absence of prior sternotomy (50% vs 33% P = .02) (Table 1). Most of the effusions were anterior (40%) or circumferential (47%). There was no association between size of effusion and location. A total of 9 patients (12%) required intervention at a mean of 15 ± 4 days from OHT (6 surgical, 3 percutaneous). Tamponade or early tamponade was seen in 5 of these patients. Post-surgical hemopericardium was suspected in 6 of these patients, while perforation from right heart biopsy was the etiology of effusion in a single patient. A majority of effusions (8/9) that required intervention were circumferential (P = .04). 21 patients continued to have an effusion for at least 1 year post transplant without hemodynamic consequence. 11 patients developed a late effusion (>1 month post OHT) effusion, also without apparent hemodynamic consequence. Conclusions: Absence of prior sternotomy was the only characteristic associated with a higher rate of effusion. Size mismatch did not predict the development of an effusion in our cohort. Most effusions were anterior or circumferential. Approximately 12% of effusions required intervention and none required intervention after the first month of transplant. Effusions requiring intervention were more likely to be circumferential.Table 1

Utility of quantitative real time PCR in detection and monitoring of viral infections in post renal transplant recipients

BackgroundViral infections cause significant morbidity and mortality in post-transplant period. A highly sensitive and specific detection tool if used may help in early diagnosis and better management in these patients. The study aimed to assess the utility of quantitative real-time polymerase chain reaction (qRT-PCR) as a diagnostic and monitoring tool for viral infections in post renal transplant patients. MethodsA quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect EBV and CMV infection in 50 patients on 1st, 2nd, 3rd, and after 6 months of renal transplantation. ResultsCMV infection was found in 34%, EBV in 28% of recipients, and 17% showed dual infection. Viruses were detectable after the first month of transplantation followed by symptomatic infections within first three months of follow-up, with diarrhea being the commonest symptom. These patients were also at high risk for developing other infections. Anti-thymocyte globulin (ATG) induction was a definitive risk factor for CMV/EBV infection in post operative period. ConclusionRenal transplant patients frequently develop one or more viral infections at a time. Regular monitoring with qRT-PCR and prompt antiviral therapy with reduction in immunosuppression may be an ideal approach for management of these patients.

Abstract 13819: Cancer After Heart Transplantation: Incidence, Risk Factors and Prognosis

Introduction: Malignancy is a major cause of morbidity and mortality after heart transplantation. We determined incidence, risk factors and prognosis of cancer after heart transplantation in a large single center cohort with long-term follow-up. Methods: We retrospectively analyzed all patients undergoing heart transplantation at our institution between January 1987 and December 2013. Patients who died within the first month of transplantation were excluded. All remaining patients were followed up until death or December 2014 for development of cancer. Results: Five hundred and forty-one patients were followed up for a mean of 10.7 ± 6.7 years. Cancer was diagnosed in 181 patients, at a mean of 7.7 ± 5.0 years after transplantation. Cumulative incidence of any cancer at 1, 5 and 10 years was 2 %, 14 % and 29 %, respectively. Almost half of all cancers were skin tumors (83 patients), squamous-cell carcinoma (57 patients) being more frequent than basal-cell carcinoma (51 patients). The most frequent non-skin cancer was lung cancer (41 patients), followed by lymphoma (30 patients) and prostate cancer (25 patients). Several patients had more than one cancer. Age at transplantation older than 50 years (HR 3.3, p &lt; 0.001), male gender (HR 2.1, p = 0.001), ischemic etiology for transplantation (HR 1.4, p = 0.02), transplantation era before 2000 (HR 1.4, p=0.04), azathioprine versus mycophenolate (HR 1.4, p= 0.04) and cyclosporine versus tacrolimus as initial immunosuppression (HR 1.7, p = 0.005) were significant risk factors for post-transplant malignancy in a univariate Cox proportional hazards model. Of these, age at transplantation and male gender were independent risk factors in multivariate analysis. Median patient survival after diagnosis of cancer was 2.9 years for patients with non-skin cancer, versus 13.1 years for patients with only skin cancer (p &lt; 0.001). Conclusions: This study highlights the importance of cancer after heart transplantation. Older recipient age at transplantation and male gender were independent risk factors in multivariate analysis. Strategies to individualize immunosuppression according to the patient’s needs could potentially help reduce this important cause of morbidity and mortality after heart transplantation.

Gut microbiota and tacrolimus dosing in kidney transplantation.

Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5) or did not require such an increase (Dose Stable Group, n=14). We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2±1.1 mg/day vs. 3.8±0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts) but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6±2.4 mg/day vs. 3.3±1.5 mg/day, respectively, P<0.001). Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses). Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01) and had a coefficient±standard error of 1.0±0.6 (P=0.08) after multivariable linear regression. Our novel observations may help further explain inter-individual differences in tacrolimus dosing to achieve therapeutic levels.

Hematopoietic stem-cell transplantation in the developing world: experience from a center in Western India.

We describe our experience of first 50 consecutive hematopoietic stem-cell transplants (HSCT) done between 2007 and 2012 at the Apollo Hospital, Gandhinagar, 35 autologous HSCT and 15 allogeneic HSCT. Indications for autologous transplant were multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, and acute myeloid leukemia, and indications for allogeneic transplants were thalassemia major, aplastic anaemia, chronic myeloid leukemia, and acute lymphoblastic and myeloid leukaemia. The median age of autologous and allogeneic patient's cohort was 50 years and 21 years, respectively. Median follow-up period for all patients was 39 months. Major early complications were infections, mucositis, acute graft versus host disease, and venoocclusive disease. All of our allogeneic and autologous transplant patients survived during the first month of transplant. Transplant related mortality (TRM) was 20% (N = 3) in our allogeneic and 3% (N = 1) in autologous patients. Causes of these deaths were disease relapse, sepsis, hemorrhagic complications, and GVHD. 46% of our autologous and 47% of our allogeneic patients are in complete remission phase after a median follow-up of 39 months. 34% of our autologous patients and 13% of our allogeneic patients had disease relapse. Overall survival rate in our autologous and allogeneic patients is 65.7% and 57.1%, respectively. Our results are comparable to many national and international published reports.

Transplant nephrectomy - A single-center experience.

Transplant nephrectomy (TN) is associated with significant morbidity and mortality and influences the outcome of subsequent renal transplantation. The aim of this study was to identify the reasons for TN in a single transplant center in the United Kingdom and to determine the complication rate, effect on relisting and re-transplantation. We studied all the TNs in our center from January 2000 to December 2011. Detailed information including cause of allograft failure and reason for TN were analyzed. Of 602 renal transplants performed at our center during the period of the study, 42 TNs were performed on 38 (6%) patients (24 men and 14 women). The median age of the patients at the time of transplantation who subsequently underwent TN was 56 years (range: 28-73 years) and 71% of the allografts were donated after circulatory death. The mean human leucocyte antigen mismatch for these patients was 2.3. The most commonly used immunosuppression was a combination of prednisolone, mycophenolate and tacrolimus, which was used in 50% of the patients. Twenty-five (60%) of the TNs in this series were for allografts failing during the first month of transplantation. The most common indication for the TN was graft thrombosis (50%), with an overall in-hospital mortality rate of 9.5% and a morbidity rate of 31%. Seven of 19 patients listed underwent successful re-transplantation. Although TN is associated with a risk of significant morbidity and mortality, it does not preclude from listing for re-transplantation. The difficulty of access to complete information about transplant failures and TN highlights the need for a national registry.

The effect of CYP3A5 polymorphism on cyclosporine plasma level in Egyptian renal transplant recipients

Cyclosporine (CsA) and tacrolimus are immunosuppressants used for the prevention of rejection of transplanted organs. The genes encoding cytochrome (CYP) P450 enzymes, CYP3A4, and CYP3A5 are the main ones involved in the pharmacokinetics of calcinurin inhibitors (CNI). Several single nucleotide polymorphisms were identified in these genes such as CYP3A5*3 (6986A>G). The association of the CYP3A5*3/*3 genotype with decreased clearance of its substrates was reported among different ethnic populations. This study aims to evaluate the effect of CYP3A5*3 polymorphism on CsA plasma levels in Egyptian renal transplant patients at the first week and first month of transplantation. A total of 44 renal transplant recipients receiving CsA were genotyped for CYP3A5*3 polymorphism. The C0 and C2 of CsA were measured and their relationships with CYP3A5*3 genotypes were investigated. CYP3A5*3 allele was present in six patients and the CsA level didn’t differ significantly between the CYP3A5*3 the CYP3A5*1 allele carriers at the first week and the first month post transplantation. Large-scale studies with the involvement of multiple genetic markers claimed to affect the CsA pharmacokinetics are highly recommended to elucidate their pharmacogenetic role in renal transplant patients.

Usefulness of the Secretory Unit of Islet Transplant Objects (SUITO) Index for Evaluation of Clinical Autologous Islet Transplantation

Background Assessing the engrafted islet mass is important in evaluating the efficacy of islet transplantation. We previously demonstrated that the average secretory unit of islet transplant objects (SUITO) index within 1 month of allogeneic islet transplantation was an excellent predictor of insulin independence. However, the usefulness of the SUITO index for evaluating autologous islet transplantation has not been explored. The purpose of the present study was to assess the relationship between the SUITO index and clinical outcomes after total pancreatectomy followed by autologous islet transplantation. Methods We performed 27 total pancreatectomies followed by autologous islet transplantation from October 2006 to January 2011. Cases were divided into an insulin-independent group (IIG; n = 12) and an insulin-dependent group (lDG; n = 15). The SUITO index was calculated by the formula [fasting C-peptide (ng/mL)/fasting glucose (mg/dL) −63] × 1,500. The average SUITO index within the first month of transplantation except for days 0, 1, and 2, maximum SUITO index, and most recent SUITO index were calculated in each case, and values were compared between the IIG and the IDG. Results The average SUITO index within 1 month was significantly higher in the IIG than in the IDG (24.6 ± 3.4 vs 14.9 ± 2.0, respectively; P < .02). The maximum SUITO indices were 45.7 ± 7.7 in the IIG and 30.1 ± 8.1 in the IDG (not significant), and the recent SUITO indices were 36.9 ± 6.7 in the IIG and 22.8 ± 6.1 in the IDG (not significant). Conclusions The average SUITO index within 1 month was an excellent predictor of insulin independence after total pancreatectomy followed by autologous islet transplantation.

Trimethoprim-sulfamethoxazole induced acute interstitial nephritis in renal allografts; clinical course and outcome

Acute interstitial nephritis (AIN) secondary to trimethoprim-sulfamethoxazole (TMP-SMX) is well documented as a cause of acute renal failure in native kidneys. TMP-SMX is the standard prophylactic agent against pneumocystis carinii (PCP) used in the early post-transplant period, however, it has to date only been indirectly associated with AIN in renal allografts. We describe eleven renal transplant patients with acute allograft dysfunction in whom a transplant biopsy demonstrated primary histopathologic features of allergic AIN, all of whom were receiving TMP-SMX in addition to other medications known to cause AIN. All cases occurred within 1 month of transplantation and accounted for 2.12% (11/518) of the total number of transplant biopsies performed during the study period. However, this figure increased to 10.1% (11/109) when those biopsies performed for early allograft dysfunction (< 1 month) were taken into account. After discontinuation of TMP- SMX alone, all patients had an immediate improvement in serum creatinine with excellent long term allograft function - mean improvement of serum creatinine from 465 micromol/l to 136 micromol/l at last follow-up (range 15 - 55 months). AIN secondary to TMP-SMX, although an uncommon cause of allograft dysfunction over the study period, accounted for over 10% of cases of allograft dysfunction within the first month of transplantation. Therefore, a high degree of clinical suspicion for TMP-SMX-induced AIN is warranted when confronted with early acute allograft dysfunction.

Avoidance of Calcineurin Inhibitors With Use of Proliferation Signal Inhibitors in De Novo Heart Transplantation With Renal Failure

This study describes our experience with proliferation signal inhibitors in de novo heart transplant recipients with significant renal impairment. To circumvent further nephrotoxicity, calcineurin inhibitors were avoided in the peri-operative period. Immunosuppression in 20 patients was with a proliferation signal inhibitor (sirolimus, 14; everolimus, 6), an anti-mitotic drug, and corticosteroids from the time of transplantation. Induction was used in 9 patients (45%). All patients had preoperative significant renal dysfunction (mean glomerular filtration rate <30 ml/min/1.73 m(2)), and 4 patients required dialysis. Post-operatively, the glomerular filtration rate significantly increased (>65 ml/min/1.73 m(2) at Month 1, remaining stable thereafter). No patients required dialysis after the first month of transplantation. Mean follow-up was 500 days. Rejection episodes occurred in 11 patients (55%), and 4 patients died (2 of rejection, although 1 death occurred 48 days after conversion to conventional treatment with tacrolimus). Half of the patients were eventually converted to conventional calcineurin-inhibitor therapy because of proliferation signal inhibitor adverse events. Although this immunosuppressive approach was associated with a somewhat high rate of rejection and frequent side effects, it represents an attractive alternative in the complicated peri-operative setting of patients with significant renal impairment. This approach could serve as a temporary bridge to a conventional treatment.

The Effects of Body Mass Index on Graft Survival in Adult Recipients Transplanted with Single Pediatric Kidneys

Background: There is insufficient data on the impact of recipient body mass index (BMI) on the long-term graft survival of adult patients transplanted with single pediatric kidneys. Methods: We performed a retrospective analysis of adult patients transplanted with single pediatric kidneys at our center. The recipients were classified into 2 groups: group 1 (BMI ≥30) and group 2 (BMI <30). Donor/recipient demographics, postoperative outcomes and survival rates were compared between the 2 groups. Results: There was no significant difference in donor/recipient demographics between the 2 groups. In group 1, the death-censored graft survival (DCGS) at 1, 3 and 5 years was 90% at all 3 time points, and in group 2 it was 86, 68 and 60%, respectively (p = 0.05). The mean glomerular filtration rate (with standard deviation in parentheses) at 1, 3 and 5 years was, respectively, 55 (15), 59 (19) and 55 (28) ml/min for group 1, compared to 65 (28), 69 (23) and 67 (20) ml/min in group 2 (p = NS). Multivariate analysis revealed a hazard ratio of 5.12 (95% confidence interval 1.06–24.7; p = 0.04) for graft loss in nonobese patients when compared to obese patients. Obese patients had an increased risk for acute rejections within the first month of transplant (p = 0.02). Conclusion: Patients with a BMI ≥30 transplanted with single pediatric kidneys have better DCGS rates when compared to nonobese patients.