Indications and efficacy of conversion from tacrolimus‐ to sirolimus‐based immunosuppression in pediatric patients who underwent liver transplantation for unresectable hepatoblastoma

SRL‐based immunosuppressive strategies in pediatric liver transplantation are not clearly defined, especially within the first year after liver transplant. TAC is the more common, traditional immunosuppressant used. However, SRL may modulate TAC‐associated kidney injury and may also have antiproliferative properties that are valuable in the management of patients following liver transplantation for HB. We sought to determine whether early conversion from TAC to SRL was safe, effective, and beneficial in a subset of liver transplant recipients with unresectable HB exposed to CDDP‐based chemotherapy. Between 2008 and 2013, six patients were transplanted for unresectable HB. All patients received at least one cycle of CDDP‐based chemotherapy prior to transplant. All patients were switched from TAC‐ to SRL‐based immunosuppression within 1 year of transplant. Five patients had improvement in their mGFR, while one patient had a slight decline. The improvement in mGFR was statistically significant. No adverse events were identified. Three patients had BPAR that responded to pulsed steroids. Historical controls showed similar rates of BPAR within the first year after transplant. There were no identified HB recurrences in the follow‐up time period. Conversion from TAC to SRL appears to be safe and effective in this selected group of pediatric liver transplant recipients without adverse reaction or HB recurrences.     

Stable long‐term renal function after pediatric liver transplantation

Herlenius G, Hansson S, Krantz M, Olausson M, Kullberg‐Lindh C, Friman S. Stable long‐term renal function after pediatric liver transplantation.
Pediatr Transplantation 2010: 14:409–416. © 2010 John Wiley & Sons A/S. Abstract: Long‐term exposure to calcineurin inhibitors increases the risk of CKD in children after LT. The aims of this study were to study renal function by measuring GFRm before and yearly after LT, to describe the prevalence of CKD (stage III: GFR 30–60 mL/min/1.73 m²) and to investigate if age and underlying liver disease had an impact on long‐term renal function. Thirty‐six patients with a median age of 2.9 years (0.1–16 yr) were studied. Median follow‐up was 6.5 (2–14 yr). GFRm decreased significantly during the first six months post‐transplantation with 23% (p < 0.001). Thereafter renal function stabilized. At six months, 17% (n = 5) of the children presented CKD stage III and at five yr the prevalence of CKD III was 18% in 29 children. However, in 13 children with a 10‐year follow‐up it was 0%. None of the children required renal replacement therapy after LT. When analyzing renal function of those children younger than two yr (n = 14) and older than two yr (n = 17) at the time of transplantation, we found that in both cohorts the filtration rate remained remarkably stable during the five‐yr observational period. However, there was a statistically significant (p < 0.05) difference in the percentual decrease in GFRm between the groups during the first six months after LT 13% and 31%, respectively. Baseline GFRm according to diagnosis did not differ between the groups. During the first six months after LT, patients transplanted for hepatic malignancy (n = 6) and those with metabolic liver disease (n = 4) had a percentage loss of GFRm of 32% and 35%, respectively. The corresponding loss of GFRm in patients with other diseases was 10‐19%. Six months post‐transplantation mean GFRm in the group with malignant liver disease was 65 ± 15 mL/min/1.73 m² and in the group with other diseases (n = 24) 82 ± 17 mL/min/1.73 m² (p < 0.05). At one, three and five yr post‐transplantation there was no longer a statistically significant difference between these cohorts. Our findings suggest that there can be a long‐term recovery of renal function after LT in children.     

Comparison of parameters of chronic kidney disease following paediatric preemptive versus non‐preemptive renal transplantation

Sinha R, Marks SD. Comparison of parameters of chronic kidney disease following paediatric preemptive versus non‐preemptive renal transplantation.
Pediatr Transplantation 2010: 14:583–588. © 2010 John Wiley & Sons A/S. Abstract: PRT is the preferred modality for renal replacement therapy in children. Despite this, there are no studies CKD parameters as per K/DOQI criteria between PRT and NPRT in children. This was a single‐centre cross‐sectional study of RTR with at least one yr of post‐transplant follow‐up. CKD parameters as per K/DOQI were compared between PRT and NPRT. Thirty percent (39/129) of our study population was PRT. Despite similar baseline characteristics at the time of transplantation and similar post‐transplantation follow‐up period, a significantly lower proportion of PRT (1, 2%) were in Stage 4 CKD in contrast to NPRT (14, 16%); p = 0.03. This was also reflected in better CKD parameters among PRT with significantly lower incidences of hypertension and acidosis (p = 0.02). CKD medications were also more commonly prescribed in NPRT (p = 0.002). We demonstrated improved CKD parameters and lower use of CKD medications among PRT when compared with NPRT. This finding should act as an added impetus for PRT programmes.     

Impacts of donor‐specific anti‐HLA antibodies and antibody‐mediated rejection on outcomes after intestinal transplantation in children

AMR is a risk factor for graft failure after SBTx. We studied impact of DSAs and AMR in 22 children transplanted between 2008 and 2012 (11 isolated SBTx, 10 liver inclusive Tx, and one modified multivisceral Tx). Three patients never developed DSA, but DSAs were found in seven in the pre‐Tx period and de novo post‐Tx in 19 children. Pathology revealed cellular rejection (15/19), with vascular changes and C4d+. Patients were treated with IV immunoglobulins, plasmapheresis, and steroids. Rescue therapy included antithymocyte globulins, rituximab, eculizumab, and bortezomib. Pathology and graft function normalized in 13 patients, graft loss occurred in two, and death in seven. At the end of the follow‐up, 15 children were alive (68%), 13 with functioning graft (59%). Prognosis factors for poor outcome after Tx were the presence of symptoms at AMR suspicion (P +.033). DSAs were often found following SBTx, mostly de novo. Resistant ACR or severe AMR is still difficult to differentiate, with a high need for immunosuppression in both. DSAs may precede development of severe disease and pathology features on the graft: relationship and correlation need to be better investigated with larger groups before and after Tx.     

Renal function after combined liver‐kidney transplantation: A longitudinal study of pediatric and adult patients

It has been proposed that the liver protects the kidney in CLKT. However, few studies have examined long‐term renal function after CLKT and contrasted renal function of CLKT patients to KT patients beyond one year after transplantation. We studied long‐term renal function of CLKT patients and compared renal function of CLKT patients to KT patients between one and five years after transplantation. Patients who underwent CLKT between 1993 and 2011 were included (n = 34; 11 children and 23 adults). Ninety‐six (27 children and 69 adults) KT patients were selected as controls. GFR was estimated (eGFR) and measured (mGFR) with ⁵¹Cr‐EDTA clearance. Mean mGFR was 63 at one and 70 at ten years after pediatric CLKT. Mean eGFR was 75 at one and 50 at ten years after adult CLKT. Difference in mean mGFR between pediatric CLKT and KT patients was 8 (95% CI ?7 to 23) and 11 (95% CI ?4 to 26) at one and five years after transplantation, respectively. Difference in mean eGFR between adult CLKT and KT patients was 8 (95% CI ?5 to 20) and 1 (95% CI ?10 to 12) at one and five years after transplantation, respectively. Longitudinal changes in GFRs were somewhat similar in CLKT and KT patients in both age‐groups but pediatric CLKT patients had on average higher GFRs than pediatric KT patients. In long‐term follow‐up, renal function remains stable in pediatric CLKT patients but declines in adult CLKT patients.     

Glomerular filtration rate in liver transplant for unresectable hepatoblastoma

Most children with hepatoblastoma manifest, at the time of LT, a decrease in renal function due to chemotherapy that could be further deteriorated by the use of calcineurin inhibitors. The purpose of this work was to examine the long‐term follow‐up of renal function in a cohort of children transplanted for unresectable hepatoblastoma. We present a retrospective observational study of 10 pediatric patients who received a LT for unresectable hepatoblastoma between 1996 and 2016. All patients included in this study were followed up on a regular basis and were assessed for GFR before transplantation and at least once a year during follow‐up. All patients received standardized chemotherapy treatment for hepatoblastoma and immunosuppression according to hospital protocols. There was a marked decrease in GFR at the time of the LT in five patients presenting renal complications during the pretransplant cycles of chemotherapy. Three patients, one of them with prior kidney involvement, presented complications after LT, namely acute kidney failure and decrease in GFR. Those patients who presented with the lowest GFR at the time of LT eventually recovered renal function at levels similar to the rest of the group on follow‐up. Chemotherapy‐induced nephrotoxicity is a concern in patients treated for hepatoblastoma. Some individuals will develop low GFR after chemotherapy; therefore, strict follow‐up is recommended, as low GFR may affect the doses of subsequent chemotherapy and immunosuppression. Stabilization of GFR levels and occasional improvement can be observed in the post‐transplant period.     

Long‐term outcome following pediatric liver transplantation for metabolic disorders

Stevenson T, Millan MT, Wayman K, Berquist WE, Sarwal M, Johnston EE, Esquivel CO, Enns GM. Long‐term outcome following pediatric liver transplantation for metabolic disorders.
Pediatr Transplant 2010:14:268–275. © 2009 John Wiley & Sons, A/S. Abstract: In order to determine long‐term outcome, including survival, growth and development, following liver transplantation in children with metabolic disorders, we retrospectively reviewed charts of 54 children with metabolic disorders evaluated from 1989–2005 for presenting symptoms, transplantation timing and indications, survival, metabolic parameters, growth, and development. Thirty‐three patients underwent liver transplantation (12 received combined liver–kidney transplants) at a median age of 21 months. At a median follow‐up of 3.6 yr, patient survival was 100%, and liver and kidney allograft survival was 92%, and 100%, respectively. For the group as a whole, weight Z scores improved and body mass index at follow‐up was in the normal range. Two yr post‐transplantation, psychomotor development improved significantly (p < 0.01), but mental skills did not; however, both indices were in the low‐normal range of development. When compared to patients with biliary atresia, children with metabolic disorders showed significantly lower mental developmental scores at one and two yr post‐transplantation (p < 0.05), but psychomotor developmental scores were not significantly different. We conclude that, in patients with metabolic disorders meeting indications for transplantation, liver transplantation or combined liver–kidney transplantation (for those with accompanying renal failure) is associated with excellent long‐term survival, improved growth, and improved psychomotor development.     

Cognitive improvement in children with CKD after transplant

Icard P, Hooper SR, Gipson DS, Ferris ME. Cognitive improvement in children with CKD after transplant.
Pediatr Transplantation 2010: 14:887–890. © 2010 John Wiley & Sons A/S. Abstract: The primary purpose of this paper was to examine the cognitive functioning of children with CKD receiving transplantation to children with CKD not receiving transplantation, and a healthy control group. The sample included six children with CKD receiving transplant, 28 children with CKD being treated conservatively, and 23 healthy controls. All participants were administered intellectual (IQ) or developmental assessments at baseline and at a one‐yr follow‐up. Results revealed that children with CKD who had received transplant showed a significant increase in their intellectual/developmental functioning post transplant compared to children with CKD not receiving transplant. Although their overall intellectual/developmental level was not fully normalized, when compared with the healthy control group, the change scores for the transplant group reflected over a 12 point increase, moving the group from the borderline range to the low average range of functioning. In this regard, pediatric transplantation appears to have a positive impact on the intellectual and developmental functioning of children with CKD.     

A longitudinal retrospective analysis of left ventricular mass in a cohort of pediatric kidney transplant recipients

Childhood end‐stage kidney disease is associated with increased risk for early adulthood cardiovascular (CV) morbidity and mortality. Increased LVM is an early indicator of CV disease. Previous studies have suggested that LVM decreases after kidney transplantation; however, trends have been inconsistent. A single center retrospective longitudinal cohort analysis of LVM, documented annually, starting before kidney transplantation for up to 10 yr after transplantation was performed. BP documented by annual 24‐h ambulatory monitoring studies, and BMI values were also reviewed. Twenty‐seven children followed for a mean period of 5.3 yr were included. Depending on definition of LVH, its prevalence pretransplant and in the first years post‐transplant was up to 33% dropping to 0–25% thereafter. Individual longitudinal LVM z‐score trends were highly variable but generally trended toward the mean immediately after transplant and toward negative values in the following years. BP was stable during the follow‐up period while mean annual BMI increased in the first‐year post‐transplant but declined thereafter. In a cohort of pediatric renal transplant recipients, prevalence of LVH decreased after transplant; however, individual longitudinal LVM trends were highly variable among patients. Prospective studies are needed to correlate individual LVM trends with outcomes.     

Outcomes of children receiving en bloc renal transplants from small pediatric donors

The utilization of en bloc renal allografts from small pediatric donors has been adopted as an effective strategy to expand the organ donor pool in adult recipients. Data in children are limited. The aim of our study is to describe the outcomes of en bloc renal transplants in children from our center. Medical records of children receiving pediatric en bloc renal transplants at our institution from January 2007 were abstracted. Data collected included recipient and donor demographics, operative technique and complications, and post‐operative studies. Eight children received en bloc renal transplants at a median age of 17 yr; median follow‐up was 0.9 yr. Donor body weight ranged from 4 to 22 kg. One kidney was lost to intra‐operative thrombosis, while the other kidney from this en bloc graft remained viable. All grafts showed increased renal size at follow‐up ultrasound. Surveillance biopsies showed glomerulomegaly in two patients. At last follow‐up, the median eGFR was 130 mL/min/1.73 m². The urinary protein to creatinine ratio was normal in four of seven patients. Our data suggest that in experienced centers, en bloc renal transplantation from young donors into pediatric recipients is effective. Long‐term follow‐up to monitor for complications, including hyperfiltration injury, is warranted.     

Long-term outcome of deceased donor renal transplantation in pediatric recipients: A single-center experience from a developing country

Kute VB, Trivedi HL, Vanikar AV, Shah PR, Gumber MR, Patel HV, Munjappa BC, Modi PR, Gera DN. Long‐term outcome of deceased donor renal transplantation in pediatric recipients: A single‐center experience from a developing country Abstract: RTx is best treatment for children with ESRD. Data scarcity on DDRTx outcome in children prompted us to review our experience. This study was undertaken to evaluate patient/graft survival, function vis‐a‐vis SCr, rejection episodes, and mortality in DDRTx performed in 37 children between 1998 and 2011. The most common recipient diseases leading to ESRD were congenital anomalies of kidney and urinary tract (48.6%) and chronic glomerulonephritis (18.9%). Mean recipient age was 13.8 ± 3.1 yr; 67.5% (n = 25) were men. Mean donor age was 38.8 ± 18.6 yr; 48.5% (n = 18) were men. Mean dialysis duration pre‐transplantation was 15.5 ± 3.5 months. All recipients received r‐ATG, and triple immunosuppression. Over a mean follow‐up of 3.93 ± 3.5 yr, patient and graft survival rates were 72.9% (n = 27) and 83.7% (n = 31), respectively, with a mean SCr of 1.1 mg/dL; 21.6% (n = 8) of patients had acute rejection episodes; 24.3% (n = 9) of patients had DGF. A total of 27% (n = 10) patients died, mainly owing to infections (n = 6) and cardiovascular disease (n = 3). DDRTx is a viable option for children and achieves acceptable graft function with patient/graft survival over long‐term follow‐up, encouraging use of this approach.     

Post-transplantation lymphoproliferative disorder in pediatric kidney-transplant recipients - A national study

Cleper R, Ben Shalom E, Landau D, Weissman I, Krause I, Konen O, Rahamimov R, Mor E, Bar‐Nathan N, Frishberg Y, Davidovits M. Post‐transplantation lymphoproliferative disorder in pediatric kidney‐transplant recipients – A national study. Abstract: PTLD is the most common malignancy in pediatric kidney‐transplant recipients. We examined the prevalence, clinical features, and outcome of PTLD in Israel. Twelve (4.4%) of 272 pediatric (<19 yr) kidney‐transplant recipients retrieved from a search of the NIKTR for 1991–2008 had acquired PTLD at a median of 3.2 yr post‐transplantation. PTLD‐affected patients were younger at transplantation (4.2 vs. 12.5 yr, p = 0.02), had a higher rate of OKT3 therapy for acute rejection (25% vs. 4%, p = 0.015), and 5/12 were EBV‐seropositive at transplantation. Graft dysfunction was the presenting sign in six (50%). PTLD was predominantly abdominal (83%) and B‐cell type (67%); T‐cell PTLD occurred exclusively in EBV‐seropositive patients. Treatment consisted of immunosuppression cessation (6/12, 50%), antiviral agents (7/12, 58%), anti‐CD20 monoclonal antibodies (4/12, 33%), and chemotherapy (6/12, 50%). Survival was 100% in the EBV‐naïve patients and 40% in the EBV‐seropositive patients. Graft loss occurred in three of eight survivors (37.5%). PTLD‐associated mortality risk was older age: 11.2 vs. 3.4 yr, longer dialysis: 15 vs. 6.5 months, T‐cell type disease (75%), later PTLD onset: 6.35 vs. 1.9 yr post‐transplantation and era of transplantation (43% mortality before vs. 20% after 2001). Pretransplantation EBV‐seronegative status might confer a survival benefit with early detected PTLD. EBV‐seropositive patients are at risk for aggressive late‐onset lethal PTLD.     

Alemtuzumab with corticosteroid minimization for pediatric deceased donor renal transplantation: A seven‐yr experience

Alemtuzumab is a monoclonal antibody targeting CD52 receptors on B and T lymphocytes and is an effective induction agent in pediatric renal transplantation. We report a seven‐yr experience using alemtuzumab induction and steroid‐free protocol in the pediatric population as safe and effective. Twenty‐one pediatric deceased donor renal transplants were performed at a single academic institution. All received induction with single‐dose alemtuzumab and were maintained on a steroid‐free protocol using TAC and MMF immunosuppression. There were 15 males and six females in the study whose ages ranged from one to 19 yr. The average follow‐up was 32 months (range from 12 to 78.2 months and median 33.7 ± 23.7 months). All patients had immediate graft function. Graft survival was 95%, and patient survival was 100%. Mean 12 and 36 months eGFR were 63.33 ± 21.01 and 59.90 ± 15.27 mL/min/1.73m², respectively. Three patients developed acute T‐cell‐mediated rejection due to non‐adherence while no recipients developed cytomegalovirus infection, PTLD, or polyoma BK viral nephropathy. Steroid avoidance with single‐dose alemtuzumab induction provides adequate and safe immunosuppression in pediatric deceased donor renal transplant recipients receiving TAC and low‐dose MMF maintenance therapy.     

Sustainability of humoral responses to varicella vaccine in pediatric transplant recipients following a pretransplantation immunization strategy

Abstract: Varicella infections pose serious challenges for organ transplant recipients. To determine the safety and immunogenicity of the OMVV and determine the maintenance of OMVV responses in transplanted subjects at varying periods of immunosuppression within the first two yr following transplantation. Eligible subjects given a two‐dose OMVV pretransplantation were monitored for AE. Antibody levels were assessed at baseline, six wk post‐OMVV, pretransplantation and up to 24 months post‐transplantation. Seroprotection was defined as ≥5 gpEU. Twenty‐one seronegative children were vaccinated. Following 42 doses, no vaccine‐related serious AE occurred. Mab_titer were 17.8 (5.7–910.2) and 183.5 EU (18.8–8116.4) at six and 12 wk, respectively (p < 0.0001). Fourteen (66.7%) participants were transplanted at a median of 16 months (1.5–56) following OMVV and had Mab_titer of 27.2 EU (9.0–236.2) just prior to transplantation. Of 11 who had post‐transplantation serology, seroprotection was sustained at three, six and 12 months post‐transplantation in 10/11, 12/12 and 8/10 subjects. In five of six subjects with two‐yr follow‐up, antibody levels remained seroprotective. No breakthrough varicella infections occurred. The receipt of OMVV prior to transplantation induced humoral responses which persisted in the early months following transplantation and up to two yr post‐transplantation and was not associated with any serious adverse consequences.     

Tacrolimus‐related seizure after pediatric liver transplantation – A single‐center experience

To identify the risk factors for new‐onset seizures after pediatric LT and to assess their clinical implications and long‐term prognosis. The clinical and laboratory data of 27 consecutive children who underwent LT from January 2007 to December 2010 in our center were analyzed retrospectively. Patients were divided into seizures group and a non‐seizures group. Pre‐operative, intra‐operative, and post‐operative data were collected. Seizures occurred in four children, an incidence of 14.8%. All exhibited generalized tonic–clonic seizures within the first two wk after LT. Univariate analysis showed that the risk factors associated with seizures after pediatric LT included gender, pediatric end‐stage liver disease score before surgery, Child–Pugh score before surgery, serum total bilirubin after surgery, and trough TAC level. Multivariate analysis showed that trough TAC level was the only independent risk factor associated with the seizures. All children who experienced seizures survived with good graft function and remained seizure‐free without anti‐epileptic drugs over a mean follow‐up period of 33.7 ± 14.6 months. High trough TAC level was the predominant factor that contributed to seizures in the early post‐operative period after pediatric LT. High PELD and Child‐Pugh scores before LT and high post‐operative serum Tbil may be contributory risk factors for TAC‐related seizures.     

Cardiovascular risk factors in children after kidney transplantation – From short‐term to long‐term follow‐up

Cardiovascular‐related mortality is 100‐fold higher in pediatric renal transplant recipients than in the age‐matched general population. Seventy‐seven post‐renal transplant children's charts were reviewed for cardiovascular risk factors at two and six months after transplantation (short term) and at two yr after transplantation and the last follow‐up visit (mean 7.14 ± 3.5 yr) (long term). Significant reduction was seen in cardiovascular risk factors prevalence from two months after transplantation to last follow‐up respectively: Hypertension from 52.1% to 14%, hypercholesterolemia from 48.7% to 33%, hypertriglyceridemia from 50% to 12.5%, anemia from 29.6% to 18.3%, hyperparathyroidism from 32% to 18.3% and hyperglycemia from 11.7% to 10%, and left ventricular hypertrophy from 25.8% at short term to 15%. There was an increase in the prevalence of obesity from 1.5% to 3.9% and of CKD 3–5 from 4.75% to 24%. The need for antihypertensive treatment decreased from 54% to 42%, and the percentage of patients controlled by one medication rose from 26% to 34%, whereas the percentage controlled by 2, 3, and 4 medications decreased from 21.9%, 5.5%, and 1.4% to 6%, 2%, and 0. Children after renal transplantation appear to have high rates of cardiovascular risk factors, mainly on short‐term follow‐up.     

Extended experience with a steroid minimization immunosuppression protocol in pediatric renal transplant recipients

Lau KK, Berg GM, Schjoneman YG, Perez RV, Butani L. Extended experience with a steroid minimization immunosuppression protocol in pediatric renal transplant recipients.
Pediatr Transplantation 2010: 14:488–495. © 2009 John Wiley & Sons A/S. Abstract: Purpose: To determine the safety and efficacy of a novel steroid minimization protocol after renal transplantation at a single Northern California center. Introduction: We have previously reported our experience on the short‐term outcomes in eight children using our steroid minimization protocol. Herein, we present our ongoing experience in using this regimen in 20 children. Methods: Children receiving immunosuppression with a steroid minimization protocol at our center from 1/04 – 12/08 (Group 2) were retrospectively compared with 20 controls (Group 1). Results: At one‐month follow‐up, Group 2 was observed to have lower eGFR, hemoglobin, white cell count, and cholesterol. The incidence of adverse events during the first yr was comparable. Three patients in Group 1 displayed histological evidence of acute rejection, one patient in Group 2 developed humoral rejection; another patient in Group 2 had sub‐clinical rejection. Surgical complications were observed in 20% of patients in both groups. While 10% of patients in Group 1 developed diabetes mellitus, none was observed in Group 2. Thirty and 40% of patients in Groups 1 and 2, respectively, suffered from infectious complications during the first yr. Conclusions: Our novel steroid minimization immunosuppression is safe in children and associated with no increased risk of rejection and infection.     

Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation

Olaitan OK, Zimmermann JA, Shields WP, Rodriguez-Navas G, Awan A, Mohan P, Little DM, Hickey DP. Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation.
Pediatr Transplantation 2010: 14: 87–92. © 2009 John Wiley & Sons A/S.
Abstract:  To report the long-term outcome of deceased donor kidney transplantation in children with emphasis on the use of an intensive initial immunosuppression protocol using R-ATG as antibody induction. Between January 1991 and December 1997, 82 deceased donor kidney transplantations were performed in 75 pediatric recipients. Mean recipient age at transplantation was 12.9 yr and the mean follow-up period was 12.6 yr. All patients received quadruple immunosuppression with steroid, cyclosporine, azathioprine, and antibody induction using R-ATG-Fresenius^®. Actual one, five, and 10 yr patient survival rates were 99%, 97%, and 94%, respectively; only one patient (1.2%) developed PTLD. Actual one, five, and 10 yr overall graft survival rates were 84%, 71%, and 50%, respectively; there were five cases (6%) of graft thrombosis and the actual immunological graft survival rates were 91%, 78%, and 63% at one, five, and 10 yr, respectively. The use of an intensive initial immunosuppression protocol with R-ATG as antibody induction is safe and effective in pediatric recipients of deceased donor kidneys with excellent immunological graft survival without an increase in PTLD or other neoplasms over a minimum 10-yr follow up.     

Cardiovascular risk factors and cardiac disorders in long‐term survivors of pediatric liver transplantation

The MetS and cardiovascular disease are leading causes of late morbidity in adult liver transplantation recipients; however, limited data are available in pediatric liver transplantation. A single‐center retrospective review was undertaken for patients who had a liver transplantation before 18 yr of age and were >5 yr post‐transplantation, to study the prevalence of MetS, its components, and cardiac disorders. Fifty‐eight patients were included in the study with a mean age at transplantation of 6.3 ± 6.1 yr and mean follow‐up of 14.1 ± 6.0 yr. Of the study group, 41.4% were overweight or obese, with ongoing prednisone use and increased duration of follow‐up being significant risk factors. Fifty‐three patients had sufficient data for determining MetS, which was present in 17% of the patients. Although the prevalence of MetS is low in pediatric liver transplant recipients, it is associated with CKD and prednisone therapy (p < 0.05). Echocardiography data were available for 23 patients, of whom 43.4% had LVH and 13% had evidence of PH. The spectrum of cardiac disorders in this population is much wider than in adults.     

Towards minimizing immunosuppression in pediatric liver transplant recipients

Abstract:  Immunosuppression regimens after liver transplantation focus mainly on preventing rejection and subsequent graft loss. However, in children, morbidity and mortality rates from infections exceed those from rejection after transplant, and immunosuppression can hinder growth, renal function, and graft tolerance. We hypothesized that early steroid withdrawal, with a primary aim of TAC monotherapy would yield no penalty in terms of rejection and graft loss, while reducing risks of infection and maximizing growth. We prospectively evaluated 64 consecutive pediatric liver transplant recipients. One yr patient/graft survival was 93/90%, respectively. At one yr post-transplant, 75.4% of patients were on TAC monotherapy. No deaths or graft losses were caused by infection. Sixty-one percent of patients had at least one episode of rejection, most within three months following transplant and 3.8% were treated for chronic rejection. One non-compliant adolescent died from chronic rejection. CMV, EBV, and lymphoproliferative disease rates were 3.1%, 5.3%, 1.8%, respectively. Pretransplant and one yr post-transplant glomerular filtration rates were unchanged. One yr improved catch-up growth was observed. We conclude that immunosuppression minimization after pediatric liver transplant yields no serious complications from rejection, and might confer advantages with respect to infection, renal function, growth, and is deserving of wider application and study.