Post-transplant diabetes mellitus in children following renal transplantation

Abstract:  PTDM plays a role in chronic allograft nephropathy and decreases graft and patient survival. Considering the serious outcome of chronic hyperglycemia, the importance of early recognition and the few data in children, in this retrospective analysis we studied the characteristics and risk factors of PTDM in 45 pediatric renal transplant recipients receiving Tac or CyA-based immunosuppression. Fasting blood sampling and OGTT were performed. PTDM has been developed in six patients (13%), while seven children (16%) had IGT, with the overall incidence of a glucose metabolic disorder of 29% in pediatric renal transplants. Patients in the PTDM + IGT group were younger and had higher systolic blood pressure and serum triglyceride level than children with normal glucose tolerance. Multivariate analysis identified Tac treatment, Tac trough level, steroid pulse therapy and family history of diabetes to be associated with the onset of PTDM. In pediatric renal transplants, OGTT and frequent assessment of blood glucose levels might be essential not only in the post-transplant management, but also prior to transplantation, particularly with family history of diabetes. Careful monitoring and modified protocols help to minimize the side effects of Tac and corticosteroids.     

Post‐transplant glucose status in 61 pediatric renal transplant recipients: Preliminary results of five Turkish pediatric nephrology centers

Buyan N, Bilge I, Turkmen MA, Bayrakci U, Emre S, Fidan K, Baskin E, Gok F, Bas F, Bideci A. Post‐transplant glucose status in 61 pediatric renal transplant recipients: Preliminary results of five Turkish pediatric nephrology centers.
Pediatr Transplantation 2010:14:203–211 © 2009 John Wiley & Sons A/S. Abstract: To assess the incidence, risk factors and outcomes of PTDM, a total of 61 non‐diabetic children (24 girls, 37 boys, age: 14.5 ± 2.1 yr) were examined after their first kidney transplantation (37.3 ± 21.6 months) with an OGTT. At baseline, 16 (26.2%) patients had IGT, 45 (73.8%) had NGT, and no patient had PTDM. No significant difference was shown between TAC‐ and CSA‐treated patients in terms of IGT. Higher BMI z‐scores (p = 0.011), LDL‐cholesterol (p < 0.05) and triglyceride levels (p < 0.01), HOMA‐IR (p = 0.013) and lower HOMA‐%β (p = 0.011) were significantly associated with IGT. Fifty‐four patients were re‐evaluated after six months; eight patients with baseline IGT (50%) improved to NGT, three (19%) developed PTDM requiring insulin therapy, five (31%) remained with IGT, and four patients progressed from NGT to either IGT (two) or PTDM (two). These 12 progressive patients had significantly higher total cholesterol (p < 0.05), triglycerides (p < 0.05), HOMA‐IR (p < 0.01) and lower HOMA‐%β (p < 0.0) than non‐progressive patients at baseline. We can conclude that post‐transplantation glucose abnormalities are common in Turkish pediatric kidney recipients, and higher BMI z‐scores and triglyceride concentrations are the main risk factors. Considering that the progressive patients are significantly more insulin resistant at baseline, we suggest that the utility of both HOMA‐IR and HOMA‐%β in predicting future risk of PTDM and/or IGT should be evaluated in children.     

The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus

Solid-organ transplantation is the optimal long-term treatment for most patients with end-stage organ failure. After solid-organ transplantation, short-term graft survival significantly improved (1). However, due to chronic allograft nephropathy and death with functioning graft, long-term survival has not prolonged remarkably (2). Posttransplant immunosuppressive medications consist of one of the calcineurin inhibitors in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroids. All of them have different adverse effects, among which posttransplant diabetes mellitus (PTDM) is an independent risk factor for cardiovascular (CV) events and infections causing the death of many transplant patients and it may directly contribute to graft failure (3). According to the criteria of the American Diabetes Association (4), diabetes mellitus (DM) is defined by symptoms of diabetes (polyuria and polydipsia and weight loss) plus casual plasma glucose concentration ≥ 11.1 mmol/L or fasting plasma glucose (FPG) ≥ 7.0 mmol/L or 2-h plasma glucose level ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). This metabolic disorder occurring as a complication of organ transplantation has been recognized for many years. PTDM, which is a combination of decreased insulin secretion and increased insulin resistance, develops in 4.9/15.9% of liver transplant patients, in 4.7/11.5% of kidney recipients, and in 15/17.5% of heart and lung transplants [cyclosporine A (CyA)/tacrolimus (Tac)-based regimen, respectively] (5). Risk factors of PTDM can be divided into non-modifiable and modifiable ones (6), among which the most prominent is the immunosuppressive therapy being responsible for 74% of PTDM development (7). Emphasizing the importance of the PTDM, numerous studies have determined the long-term outcome. On the basis of these studies, graft and patient survival is tendentiously (8) or significantly (9, 10) decreased for those developing PTDM.     

Post-transplant diabetes mellitus in pediatric liver transplantation

Abstract:  To determine the characteristics of pediatric liver transplant recipients who develop GI and/or PTDM, data on children undergoing their first liver transplant from the SPLIT database were analyzed (n = 1611). Recipient and donor characteristics that were evaluated included age at transplant, gender, race, primary disease, hospitalization status at transplant, BMI, recipient and donor CMV status, donor type, donor age, and primary immunosuppression. GI/PTDM was found in 214 individuals (13%) of whom 166 (78%) were diagnosed within 30 days of transplantation (early GI/PTDM). Multivariate analyses suggests that age >5 yr at transplant, hospitalization at transplant, a primary diagnosis other than BA, early steroid use, and tacrolimus use are associated with increased incidence of early GI. Routine monitoring for the development of GI and post-transplant diabetes is indicated in the short- and long-term care of children after liver transplantation.     

Tacrolimus-based immunosuppression with steroid withdrawal in pediatric kidney transplantation--4-year experience at a moderate-volume center

Tacrolimus-based immunosuppression with steroid withdrawal in pediatric kidney transplantation was pioneered at the University of Pittsburgh but is not broadly practiced at other centers. We present our 4-year experience with a modified Pittsburgh protocol at our own moderate-volume center. Seventeen pediatric kidney transplant recipients were treated with a tacrolimus-based immunosuppressive regimen involving steroid withdrawal over 6-12 post-transplant months in most cases and followed for up to 49 months. Patient and graft survival as well as graft function were excellent, and beneficial effects on several cardiovascular parameters were noted. Complications included fungal infections, glucose intolerance and post-transplant lymphoproliferative disease and were generally managed successfully. While awaiting longer-term follow-up data, we conclude that tacrolimus-based immunosuppression with steroid withdrawal in pediatric kidney transplantation is potentially beneficial and feasible even at centers managing a rather small number of recipients.     

Long‐term outcomes in pediatric liver recipients: Comparison between cyclosporin A and tacrolimus

In recent years, tacrolimus (FK506, TAC) has been increasingly utilized in liver transplantation. However, long-term risks and benefits as compared with conventional cyclosporin A (CsA) have not been fully elucidated. This retrospective study examined the potential outcome differences between TAC- and CsA-based immunosuppressive therapy in pediatric liver transplant recipients. From March 1988 to December 1996, 218 children (aged 0.1-17 yr) underwent 238 orthotopic liver transplantations; 58.7% (128/218) were under 2 yr of age at time of transplant. Initially, the maintenance immunosuppressive regimen consisted of CsA and prednisone, with antilymphocytic preparations (MALG, ATGAM, and OKT3) as induction therapy. Subsequently, TAC was used first as rescue therapy for steroid refractory rejection in CsA patients and then as maintenance immunosuppression. Fifty-seven out of the 147 CsA patients were converted to TAC for various reasons while 71 patients were placed on TAC as primary maintenance immunosuppression. 62.6 per cent (92/147) of liver recipients on CsA experienced at least one biopsy-proven acute rejection episode as compared to 50.7% (36/71) for TAC patients (p = 0.09); likewise, 34% (50/147) of CsA patients had more than one episode of rejection vs. 18.3% (13/71) for patients on TAC (p < 0.02). Rejection was the reason for conversion from CsA to TAC in 29 of 57 patients. Conversely, 19.0% (28/147) of CsA patients had to be switched to TAC for reasons not related to rejection (i.e. side-effects). The overall incidence of histologically proven chronic rejection was 7.8% (17/218). 10.9 per cent (16/147) of the children who were on CsA initially developed chronic rejection, which was significantly higher compared with one of 71 TAC recipients (p < 0.02). Of these 16 CsA patients with chronic rejection, 50.0% (8/16) underwent retransplantation for graft failure (mean interval from time of diagnosis of chronic rejection to re-transplant, 4.0 months; range 1-8 months), whereas the TAC patient has remained clinically stable with normal liver function tests after 23 months of follow-up. One year after liver transplantation, 72.8% (107/147) of CsA patients were still on steroids (mean dosage 0.20 mg/kg/d), as compared to 42.3% (30/71) of the TAC patients (mean dosage 0.14 mg/kg/d). The incidence of post-transplant lymphoproliferative disorder (PTLD) in Epstein-Barr virus (EBV)-infected patients was 2.2% (2/90), 7.0% (5/71) and 12.3% (7/57) for CsA, primary and TAC-converted groups, respectively. The overall incidence of PTLD was 6.9% (15/218). In summary, pediatric liver transplant recipients treated with TAC as primary maintenance immunosuppressive medication experienced significantly fewer episodes of rejection; especially chronic rejection, which lead to graft loss. However, the trade-off is a potential increased incidence of EBV-related PTLD in these patients.     

Living donor lobar lung transplantation: the pediatric experience

Living donor (LD) lobar lung transplantation is now an accepted alternative to cadaveric lung transplantation in selected patients with end-stage lung disease. This study reviews the Childrens Hospital Los Angeles LD experience of 17 patients (mean 13.2 +/- 2.7 yrs; range 9.3-18.5 yrs). 12 LD patients had end-stage cystic fibrosis, 4 had primary pulmonary hypertension, and 1 child had bronchiolitis obliterans. LD candidates must meet the same criteria as for cadaveric lung transplant candidates. Donor candidates are rigorously screened (physically and psychologically) prior to acceptance for lobectomy. LD patients receive the same triple immunosuppression regimen as our cadaveric recipients (prednisone, cyclosporine/FK506, and azathioprine/mycophenolate). Comparison of rejection episodes, incidence of bronchiolitis obliterans, pulmonary function tests, exercise stress tests, and cardiac catheterization data was made between LD and cadaveric lung transplantation (CL) pediatric recipients. Donor outcomes were also reviewed. In our pediatric program, the 1-year survival rate for LD recipients is currently 81%, which compares favorably with the ISHLT average of 70% for pediatric transplant patients. The incidence of rejection is about the same for LD and CL recipients, but the episodes are less severe for pediatric LD patients. There have been no histological cases of bronchiolitis obliterans syndrome in our LD recipients. Although there have been questions as to whether transplanted lobes can supply comparable pulmonary reserve to whole cadaveric lungs, the lung volumes (TLC and VC), expiratory flow rates, maximal exercise stress tests, and pulmonary artery pressures (no evidence of pulmonary hypertension) in LD patients are not significantly different to CL recipients in our institution. Besides pain from the thoracotomy, the donors have a decrease of 16% (right lower lobe donor) and 18% (left lower lobe donor) in their vital capacity. Otherwise, there have been no major complications to the donors and most have resumed their usual activities. Based on outcomes, pulmonary function tests, exercise stress tests, and hemodynamic studies as well as low donor morbidity, living donor double lobar lung transplantation is a viable alternative to cadaveric lung transplantation in selected pediatric patients with end-stage lung disease.     

The development of eosinophilic colitis after liver transplantation in children

Tacrolimus-based immunosuppression in pediatric liver transplant recipients is known to be associated with EGID. Our goal was to determine the incidence, risk factors, and characteristics of EGID in our pediatric liver transplantation program. This study was a retrospective analysis of 38 pediatric liver transplant recipients. Rectal mucosal biopsy was performed to evaluate for gastrointestinal PTLD and eosinophilic colitis. There were 14 patients (37%) who were diagnosed with eosinophilic colitis. The mean age at transplantation was 10.8 +/- 1.8 months. Those with eosinophilic colitis had a higher incidence of peripheral eosinophilia (p = 0.003) during the first two months following transplantation and had a higher EBV infection rate. Symptoms, such as diarrhea, hematochezia, and abdominal pain, became apparent after an average of three months; diagnoses were made at 6.9 +/- 2.0 months after transplantation. There were eight patients (57%) with elevated food-specific IgE levels. With food restriction treatment, the symptoms of patients improved. EGID should be considered when clinical symptoms are present, because symptoms of this disorder are similar to those of gastrointestinal PTLD. It should also be considered when peripheral eosinophila is detected or when EBV seroconversion develops during the first two months following transplantation.     

The role of quantitative Epstein-Barr virus polymerase chain reaction and preemptive immunosuppression reduction in pediatric liver transplantation: a preliminary experience.

BACKGROUND: Risk factors for the development of posttransplant lymphoproliferative disease (PTLD), a major cause of morbidity and mortality after pediatric liver transplantation, are primary Epstein-Barr virus (EBV) infection and intensity of immunosuppression. The authors assessed monitoring of EBV replication and preemptive immunosuppression reduction in pediatric liver transplant recipients. METHODS: The authors prospectively followed monthly EBV-quantitative competitive polymerase chain reaction to measure EBV replication in 23 patients who underwent liver transplant between July 1997 and November 1998. Preemptive immunosuppression reduction was instituted for significant EBV replication. Patients were followed up for at least 1 year and divided in two groups for analysis (group 1, pretransplant seronegative for EBV [13 patients]; group 2, seropositive for EBV [10 patients]). RESULTS: In group 1, 9 of 13 patients had positive polymerase chain reaction results at a mean time of 22.4 weeks after transplantation. All but one of these patients were asymptomatic. In seven of nine patients, preemptive immunosuppression reduction was undertaken without development of PTLD or rejection. In two of nine patients, immunosuppression could not be continuously reduced, and both patients experienced low-grade and medically responsive PTLD. In no patient in group 2 did an EBV-positive viral load or PTLD develop. CONCLUSIONS: Prospective longitudinal measurement of EBV by quantitative competitive polymerase chain reaction permits early detection of asymptomatic viral replication. Subsequent preemptive reduction of immunosuppression may prevent the progression to PTLD.     

Eight-year experience of pediatric heart transplantation: clinical outcome using non-invasive methods for the evaluation of acute rejection

Combined immunosuppression therapy and acute rejection surveillance after heart transplantation may influence clinical outcome. This prospective, longitudinal study investigated 27 pediatric patients (12 days to 12 yr of age; mean 3.0 yr) who underwent a post-operative regimen that included long-term treatment with cyclosporin A and azathioprine (double immunosuppression) and polyclonal anti-thymocyte serum induction therapy. Non-invasive parameters were used to diagnose acute rejection. The actuarial survival, clinical outcomes, and complications were analyzed. The actuarial survival after double immunosuppression and induction therapy with polyclonal anti-thymocyte serum was 89%, 73%, and 57% at 1, 4, and 8 yr, respectively. The rejection frequency was 2.6 episodes/patient and the infection frequency, 3.7 episodes/patient. One year after transplantation, systemic arterial hypertension was detected in 21% of patients. Hence, double immunosuppression with polyclonal anti-thymocyte serum induction therapy combined with surveillance of acute rejection with non-invasive tests may provide promising clinical outcome in pediatric heart transplant recipients.     

BK virus nephropathy in a pediatric heart transplant recipient with post‐transplant lymphoproliferative disorder: A case report and review of literature

BKV is known to cause allograft failure in kidney transplant recipients. It has been recently recognized to cause native kidney nephropathy in non‐kidney transplant recipients. This is a case report BKVN in a 15‐yr‐old HTx recipient who had PTLD and a review of pediatric cases in the literature. The patient was diagnosed with BKVN +189 months after transplantation and died thirty days after diagnosis of BKVN. We identified five other cases of BKVN in pediatric non‐kidney solid organ transplantation, of which all were HTx recipients. Overall, outcome was poor and BKV clearance was not achieved with reduction of immunosuppression and with current therapies. We strongly recommend that pediatric HTx recipients be tested for BKV infection if there is evidence of kidney dysfunction. We also recommend that they have an annual screening for BKV viruria and viremia with the assessment of kidney function.     

Liver allograft pathology in healthy pediatric liver transplant recipients

Liver transplantation offers excellent results for children with end‐stage liver disease, and efforts should be directed toward maintaining long‐term graft health. We evaluate graft pathology in healthy pediatric transplant recipients with low‐maintenance immunosuppressive medications to assess whether protocol biopsies are helpful for adapting immunosuppression and protecting long‐term graft function. Liver biopsies were performed on 60 healthy pediatric liver transplant recipients, and histological findings were correlated with laboratory, serological, and radiological results. Fourteen patients (23%) were diagnosed with acute or early chronic rejection, and immunosuppressive medications were increased in these children. Liver function tests did not correlate with histological findings. The incidence of fibrosis was 36% in transplant recipients five or more years after liver transplantation. We observed an unexpectedly high prevalence of rejection and fibrosis in children with no laboratory abnormalities, which led to changes in their immunosuppressive medications. Scheduled biopsies appear to be useful in pediatric transplant recipients with low immunosuppressive medications for early detection of morphological changes in liver transplants. Further studies are needed to evaluate whether adaption of immunosuppression helps to reduce tissue damage and the incidence of allograft dysfunction in the long term.     

Subclinical cardiovascular changes in pediatric solid organ transplant recipients: A systematic review and meta‐analysis

CV disease is a major cause of morbidity and mortality following solid organ transplantation in adults. While the prevalence of multiple cardiometabolic risk factors is increased in pediatric solid organ transplant recipients, it is not clear whether they have subclinical CV changes. cIMT, central pWV, and CAC are indicative of subclinical CV disease, and, in adults, predict future CV events. The objective of this systematic review and meta‐analysis was to investigate the prevalence of subclinical CV changes, as measured by cIMT, pWV, and CAC among pediatric solid organ transplant recipients. We searched MEDLINE^® and EMBASE and conducted meta‐analysis for studies that evaluated cIMT, central pWV, and CAC among pediatric solid organ transplant recipients (kidney, lung, intestine and liver). The search identified nine eligible studies that included a total of 259 patients and 685 healthy controls. Eight studies reported on kidney transplant recipients and one study on a combined cohort of kidney and liver transplant recipients. The mean cIMT of transplant recipients was significantly higher than that of healthy controls (mean difference = 0.05 mm, 95% CI 0.02–0.07; p < 0.0001) with an estimated pooled prevalence of elevated cIMT of 56.0% (95% CI 17.0–95.0). The one study that assessed pWV showed increased vascular stiffness in transplant recipients compared to healthy controls. No studies assessing for CAC were found. There were limited data regarding subclinical CV disease following pediatric solid organ transplantation. In conclusion, kidney transplantation in childhood is associated with a higher prevalence of subclinical CV changes compared to healthy children. Longitudinal studies are needed to determine whether children have increased CV morbidity and mortality after transplantation.     

Analysis of growth during prepubertal years in long-term survivors after pediatric orthotopic liver transplantation

BACKGROUND: Growth after pediatric liver transplantation (LT) has been the subject of reviews. The conclusions have not been consistent. OBJECTIVE: To describe post-LT growth patterns in prepubertal liver transplant recipients and identify variables affecting their growth. METHODS: Sixty-seven prepubertal transplant recipients met the inclusion criteria. Variables assessed were age, sex, pretransplant lack of growth, type of transplantation, primary diagnosis, liver and kidney function at one year post-LT, complications and retransplantation, prednisone therapy duration, allograft rejection episodes during the first year, cholesterol, triglycerides and immunosuppressive regimen. Mean follow-up was 3.5 years (range: 2-6 years). RESULTS: Growth according to baseline z-score, indications for transplantation and steroid withdrawal showed significant differences at 2 years post-LT. CONCLUSIONS: The causes of poorest z-scores in height post-LT were: height z-scores under -2.0 at transplantation, metabolic diagnosis, and use of steroids beyond 1 year post-LT.     

Rapid discontinuation of corticosteroids in pediatric renal transplantation

Abstract:  Corticosteroid immunosuppression has permitted the development of successful allotransplantation; however, corticosteroids are associated significant post-transplant complications. To circumvent these problems, we implemented a protocol of rapid discontinuation of corticosteroids in 19 consecutive pediatric primary kidney transplant recipients. Mean age at time of transplant was 13.4 (±4.5) yr, 52.6% were male, 63.2% underwent living donor transplantation. All patients were administered Thymoglobulin^® [anti-thymocyte globulin (rabbit)] as induction immunosuppression with a rapid tapering dose of corticosteroids (total of five daily doses), and maintained on mycophenolate mofetil and tacrolimus. Two patients had immediate recurrence of primary disease (FSGS), requiring further corticosteroid therapy. Otherwise, remaining 17 patients were maintained off corticosteroids, with excellent graft function; mean baseline eGFR of 112 mL/min/1.73 m² (±19) at 28 months (±14) post-transplantation. There was 100% patient and rejection-free graft survival at 27 months (range 5–58 months) post-transplantation; 47% underwent renal transplant biopsy secondary to acute rise in serum creatinine with or without worsening hypertension. All biopsies had no evidence of acute rejection; 62.5% had findings consistent with tacrolimus toxicity. Renal transplantation utilizing a rapid discontinuation of corticosteroid protocol in pediatric patients appears to be safe and effective, without increasing the risk of acute rejection or graft loss.     

Size‐reduced lung transplantation in children – an option worth to consider!

Benden C, Inci I, Weder W, Boehler A. Size‐reduced lung transplantation in children – an option worth to consider!
Pediatr Transplantation 2010: 14:529–533. © 2009 John Wiley & Sons A/S. Abstract: Lung transplantation is an accepted therapy for pediatric end‐stage lung disease. However, there is a shortage of suitable donor organs. Therefore, the use of downsized lung allografts seems a valuable option. We report our experience of downsized pediatric lung transplantation in comparison with standard full‐size pediatric lung transplantation over one decade. Pediatric recipients undergoing downsized or standard lung transplantation were included (January 1997–December 2006). We compared pretransplant clinical data and surgical and post‐operative complications and post‐transplant outcome. Ten pediatric lung transplants were performed (median patient age 15.6 yr [12.3–17.8]). Nine of 10 patients had CF. Five patients underwent standard full‐size lung transplantation; five had downsized lung transplants. “Downsized” recipients had significantly lower median height and weight Z‐scores. Donor/recipient length difference was significantly greater in the “Downsized” Group (p < 0.05). All patients had comparable post‐transplant functional outcome without additional surgical complications or morbidities in “downsized” recipients. Median post‐transplant survival was 65 months (5–77) in the “Standard” Group compared to 86 months (64–121) in the “Downsized” Group (p = 0.1). Our data suggest that downsized lung transplantation in pediatric recipients may have post‐transplant outcomes comparable to full‐size lung transplantation without significant complications.     

Results of one-year follow-up of steroid-free immunosuppression in pediatric renal transplant patients

Renal transplantation in children has traditionally required immunosuppression with multiple medications including glucocorticoids. Data collected over almost 30 yr suggest that although glucocorticoids are efficacious as part of a regimen to minimize the incidence of acute rejection episodes, their use is associated with increased risk for post-transplant hypertension, hyperlipidemia, and reduced growth rates. We desired to reduce these complications and thus used an immunosuppressive protocol including daclizumab, tacrolimus, and mycophenolate mofetil and study the efficacy of this protocol in a population with a high percentage of African-American recipients. No patient received glucocorticoids at any time post-transplant. Our results show that at 1 yr post-transplant, glomerular filtration rate, serum glucose, calcium and phosphorous metabolism, serum magnesium, and serum lipids were similar in patients receiving steroid-free and those receiving steroid-based immunosuppression. The incidence of acute rejection was similar in the two groups. Hematocrit and white blood count levels were lower 1 month after transplant in the steroid-free patients but these levels increased within several months. Systolic blood pressure was similar in the two groups, although this was achieved, in part, in the patients who received steroids by the administration of medications to lower blood pressure. Finally, tacrolimus levels were similar in the two groups, but patients receiving steroids required higher doses of tacrolimus at several time points studied during the first post-transplant year. Taken together, our data suggests that at one-year follow-up, steroid-free immunosuppression is safe, and efficacious in pediatric renal transplant recipients.     

Peripheral eosinophilia and eosinophilic gastroenteritis after pediatric liver transplantation

Reports indicate peripheral eosinophilia (PE) and gastrointestinal eosinophilic inflammation can occur after pediatric liver transplantation. The incidence of these conditions, potential risk factors, and the impact of PE and gastrointestinal eosinophilic inflammation on liver transplant outcome were determined in this pediatric liver transplant program. Medical records of liver transplant recipients from 1 to 97 and from 12 to 99 were reviewed. Fifty-seven transplants on 54 patients were performed during the study period. Fifty-three patients were evaluated; all had normal pre-transplantation peripheral eosinophil counts. PE of > 10% developed in 28% of patients. Using this definition, all such identified patients had absolute eosinophil counts of > 350/mm3. History of immediate hypersensitivity did not differ between patients with or without eosinophilia. Gastrointestinal endoscopy and biopsy was performed in 23 patients with gastrointestinal complaints. Of those, six had eosinophilic gastroenteritis and all six had PE. Compared with patients without eosinophilia, those with PE were younger at the time of transplantation (p < 0.05), had more frequent rejection (p < 0.01), were more commonly managed with tacrolimus-based immunosuppression (p < 0.001), and experienced more frequent episodes of detectable EBV viral load (p < 0.04). Patients with eosinophilic gastroenteritis were more frequently retransplanted (p < 0.006). PE associated with symptomatic eosinophilic gastroenteritis is common after pediatric liver transplantation. Age at transplant, frequency of rejection episodes, tacrolimus-based immunosuppression, and EBV viral load may be associated with the development of this condition. There may be higher rates of graft loss in such patients. Whether innate immune responsiveness or an acquired immune dysregulation accounts for these findings merits further evaluation.     

Immunosuppression in the pediatric transplant recipient

The field of pediatric solid-organ transplantation has significantly evolved since its beginnings in the early 20^th century. As advancements have led to the development of innovative surgical techniques and novel medication regimens, transplantation has now become a routine practice leading to an increase in the rates of organ recipients worldwide.The care of pediatric solid-organ transplant recipients differs from adults in several areas not only due to technically challenging surgeries, but mostly due to the complexity of their immunosuppression management. Although there is large variation of pediatric immunosuppression regimens worldwide, the use of calcineurin inhibitors, either tacrolimus or cyclosporine, still forms the backbone of immunosuppression regimens after solid-organ transplantation. Both medications are relatively well tolerated but are known to have long-term side effects, especially nephrotoxicity and neurotoxicity. The goal of care in long-term pediatric survivors of solid-organ transplant now aims to safely minimize exposure to immunosuppression and to achieve long-term graft tolerance.     

The impact of recipient BKV shedding before transplant on BKV viruria,DNAemia, and nephropathy post‐transplant: A prospective study

We previously demonstrated that detectable BKV replication in donor urine pretransplant was significantly associated with post‐transplant recipient BKV viremia. In this 4‐year prospective study, we assessed whether recipient BKV replication pretransplant was associated with post‐transplant viremia/BKV nephropathy. We studied 220 primary adult and pediatric organ transplant recipients for 490 person‐years and 2100 clinical visits. BKV viruria was detectable in 28 (16%), 26 adults and two children; and viremia in none pretransplant. Post‐transplant viruria occurred in all recipients with pretransplant BKV viruria, significantly more than in recipients without pretransplant viruria on univariate (P<.005) and multivariate analysis including type of organ transplanted and immunosuppression type (P .008). Time to post‐transplant viruria was significantly shorter in recipients with pretransplant viruria (P .01). By univariate and multivariate analysis, BKV viruria in recipients pretransplant did not impact post‐transplant BKV viremia (P=.97 and .97, respectively) even when stratified by type of organ transplant (kidney P=.6; liver P=.5). The peak serum and urine BKV PCR post‐transplant were not significantly different in patients with pretransplant BKV viruria and no one developed BK nephropathy. In conclusion, recipient BKV viruria prior to transplant predicts post‐transplant viruria but not viremia or BKV nephropathy.