Alemtuzumab induction with tacrolimus monotherapy in 25 pediatric renal transplant recipients

ALA induction in transplantation has been shown to reduce the need for maintenance immunosuppression. We report the outcome of 25 pediatric renal transplants between 2007 and 2010 using ALA induction followed by tacrolimus maintenance monotherapy. Patient ages were 1–19 yr (mean 14 ± 4.1 yr). Time of follow‐up was 7–51 months (mean 26 ± 13 months). Tacrolimus monotherapy was maintained in 48% of patients, and glucocorticoids were avoided in 80% of recipients. Mean plasma creatinine and GFR at one yr post‐transplant were 0.88 ± 0.3 mg/dL and 104.4 ± 25 mL/min/1.73m², respectively. One, two, and three‐yr actuarial patient and graft survival rates were 100%. The incidence of early AR (<12 months after transplantation) was 12%, while the incidence of late AR (after 12 months) was 16%. Forty‐four percent of the recipients recovered normal, baseline renal function after an episode of AR, and 44% had persistent renal dysfunction (plasma creatinine 1.0–1.8 mg/dL). One graft was lost four yr after transplantation due to medication non‐compliance. Four (16%) patients developed BK or CMV infection. In our experience, ALA induction with tacrolimus monotherapy resulted in excellent short‐ and mid‐term patient and graft survival in low‐immunologic risk pediatric renal transplant recipients.     

Treatment of BK virus‐associated nephropathy with CMX001 after kidney transplantation in a young child

NC, with renal failure secondary to bilateral dysplastic kidneys, received an LRD renal transplant (tx) at 17 months of age. Her early post‐tx course was complicated by persistently elevated blood polyoma BK virus DNA loads. A protocol biopsy at six months post‐transplant revealed BKVAN. Blood viral loads did not respond to decreased immunosuppression or treatment with ciprofloxacin and leflunomide. Six months post‐tx, her serum creatinine began to rise and we sought experimental therapy to prevent the loss of her graft. At seven months post‐tx, with FDA approval under an eIND, the patient was started on a 36‐wk course of treatment with the investigational drug. The patient is now more than 24 months after stopping treatment with CMX. BKV viral DNA loads remain at low, but still detectable levels. Urine viral loads have declined, but remain elevated. EBV DNA loads become undetectable. The patient's serum creatinine has declined back to a baseline of 0.5–0.7 mg/dL and has been stable for two yr. Renal function was preserved in association with the use of CMX001 to treat BKV nephropathy in a young pediatric kidney transplant recipient. There were no serious adverse events associated with the use of CMX001. This novel medication may be of value in the treatment of BKVAN in pediatric renal transplant recipients.     

Fecal pancreatic elastase‐1 in the evaluation of pancreatic function after pediatric intestinal transplantation

Fat malabsorption is common after SBT. To identify whether anatomic variant transplants differ in occurrence of exocrine pancreatic insufficiency that could contribute to fat malabsorption, we measured FPE repeatedly in 54 recipients of a SBT, ages 6.2 to 320 months. FPE determination most distant from SBT was 6.1 years. Of the 54, 39% received an isolated intestinal graft (native pancreas only), 48% received an en bloc liver‐intestinal‐pancreas graft (native and graft pancreas), and 13% received a multivisceral graft (graft pancreas only). Initial FPE was normal (>200 μg/g) in 15 of the 54 at a median of 22 (11‐61) days after SBT. Recipients of a liver‐intestine‐pancreas transplant were more likely to have normal FPE within 30 days after SBT than were isolated intestinal or multivisceral transplant recipients (47%, 19%, and 0%, respectively, P = .049). Of the remaining 39 patients, 34 eventually demonstrated a normal FPE at a median of 168 (31‐943) days after SBT. Type of SBT did not influence the likelihood of achieving a normal FPE level or time when it occurred. Five (9%) patients failed to achieve normal FPE, including 3 who died within 2 years after SBT. In conclusion, possessing both graft and native pancreas as in transplantation of an en bloc liver‐intestinal‐pancreas graft facilitates early normalization of FPE that eventually occurs in most patients irrespective of transplant type. Failure to recover normal pancreatic function may be associated with severe post‐transplant complications.     

Outcomes in pediatric hepatitis C transplant recipients: Analysis of the UNOS database

HCV may lead to the development of ESLD in late childhood and, consequently, contributes to the need for liver transplantation. The aim of this study was to examine post‐transplant outcomes in HCV‐positive pediatric patients with ESLD from any cause and to determine the impact of the PELD scoring system, introduced in February 2002, on post‐transplant patient and graft survival. A retrospective analysis of the UNOS database from 1994 to 2010 was performed to assess graft and patient survival in pediatric HCV‐seropositive liver transplant recipients. Graft survival and patient survival comparing subjects in the pre‐PELD era and post‐PELD era were analyzed using Kaplan–Meier statistics. Factors associated with survival were identified using Cox regression analysis. Of 120 pediatric HCV transplant recipients, 80 were transplanted in the pre‐PELD era and 40 were transplanted post‐PELD. Median serum total bilirubin, INR, and creatinine were 4.8 mg/dL, 1.6, and 0.7 mg/dL in the pre‐PELD era vs. 5.5 mg/dL, 1.7, and 0.6 mg/mL, respectively, in the post‐PELD era (p NS). One‐yr graft survival in the pre‐PELD vs. post‐PELD era was 65.0% and 89.7%, respectively (p < 0.01); corresponding three‐yr graft survival was 57.3% vs. 76.2% (p = 0.04). One‐yr patient survival in the pre‐PELD vs. post‐PELD era was 79.0% and 97.5%, respectively (p < 0.01); corresponding three‐yr survival was 79.0% vs. 89.4% (p = 0.17). Twenty‐eight patients (23.3%) were retransplanted: 24 (30%) in the pre‐PELD era (median time to retransplant 272 days) and four (10%) in the post‐PELD era (median time to retransplant 586 days). Early follow‐up demonstrates a trend toward improved pediatric HCV liver transplant graft and patient survival in the post‐PELD era. Superior outcomes may be attributed to pretransplant factors, improved surgical technique and better treatment options for HCV infection.     

Single‐center experience in pediatric renal transplantation using thymoglobulin induction and steroid minimization

Our center has offered thymoglobulin induction with steroid minimization to our pediatric renal transplant patients for the last 10 yr. Steroid minimization or avoidance has shown favorable results in survival, kidney function, and growth in previous studies of pediatric patients. We report our experience with this protocol over the past 10 yr with respect to patient/graft survival, acute rejection episodes, renal function, linear growth, bone density, cardiovascular risk factors, and opportunistic infections. A retrospective chart review was performed for pediatric renal transplant patients on the steroid‐minimized protocol between January 2002 and December 2011 on an intention to treat basis. Patient demographics, height, weight, serum creatinine, iGFR, biopsies, and survival data were collected. Height and weight z‐scores were calculated with EpiInfo 7, using the CDC 2000 growth charts. Survival was calculated using Kaplan–Meier analysis. eGFR was calculated using the original and modified Schwartz equations. Forty‐four pediatric patients were identified, aged 13 months to 19 yr. Five‐yr survival was 95.5% for males and 94.4% for females. Only five patients had biopsy‐proven ACR, two of which were at more than 12 months post‐transplantation. Height delta z‐scores from transplant to one, three, and five yr were 0.34, 0.38, and 0.79, respectively. Weight delta z‐scores from transplant to one, three, and five yr were 0.87, 0.79, and 0.84, respectively. Mean original Schwartz eGFR was 84.3 ± 15.8 mL/min/1.73 m², modified Schwartz eGFR was 59.3 ± 11.5 mL/min/1.73 m², and iGFR was 64.2 ± 8.5 mL/min/1.73 m² at three yr. Of 18 subjects who had a bone density exam, none had a z‐score less than ?2 on DEXA exam at one‐yr post‐transplantation. Fifty‐one percent of patients were on antihypertensives at the time of transplant compared with 43% at one‐yr post‐transplantation. Three yr post‐transplantation, the average LDL was <100 mg/dL, and average total cholesterol was <200 mg/dL. There were no clinical episodes of EBV or CMV infection. A steroid‐minimized protocol with thymoglobulin induction is safe and provides favorable improvement in linear growth, stable graft function, stable or improved cardiovascular risk factors, and normal bone density in pediatric renal transplant patients.     

Neurocognitive outcomes at kindergarten entry after liver transplantation at <3 yr of age

This prospective inception cohort study determines kindergarten‐entry neurocognitive abilities and explores their predictors following liver transplantation at age <3 yr. Of 52 children transplanted (1999–2008), 33 (89.2%) of 37 eligible survivors had psychological assessment at age 54.7 (8.4) months: 21 with biliary atresia, seven chronic cholestasis, and five acute liver failure. Neurocognitive scores (mean [s.d.], 100 [15]) as tested by a pediatric‐experienced psychologist did not differ in relation to age group at transplant (≤12 months and >12 months): FSIQ, 93.9 (17.1); verbal (VIQ), 95.3 (16.5); performance (PIQ), 94.3 (18.1); and VMI, 90.5 (15.9), with >70% having scores ≥85, average or above. Adverse predictors from the pretransplant, transplant, and post‐transplant (30 days) periods using univariate linear regressions for FSIQ were post‐transplant use of inotropes, p = 0.029; longer transplant warm ischemia time, p = 0.035; and post‐transplant highest serum creatinine, (p = 0.04). For PIQ, they were pretransplant encephalopathy, p = 0.027; post‐transplant highest serum creatinine, p = 0.034; and post‐transplant inotrope use, p = 0.037. For VMI, they were number of post‐transplant infections, p = 0.019; post‐transplant highest serum creatinine, p = 0.025; and lower family socioeconomic index, p = 0.039. Changes in care addressing modifiable predictors, including reducing acute post‐transplant illness, pretransplant encephalopathy, transplant warm ischemia times, and preserving renal function, may improve neurocognitive outcomes.     

Success with plasmapheresis treatment for recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients

FSGS recurs in approximately 30% of transplanted kidneys and may lead to graft loss. We retrospectively examined the efficacy of early and intensive PP without additional IS in pediatric kidney transplant patients with recurrent FSGS at our center. Seven of 24 patients (29%) had nephrotic proteinuria and histologic evidence of FSGS recurrence within 1–5 days post‐transplantation. PP was initiated early after transplantation and initially performed daily until sustained decline in proteinuria. PP frequency was then individually tapered according to proteinuria. Recurrent FSGS in all seven patients responded to a four‐ to 32‐wk course of PP. Two of seven patients had a second recurrence of FSGS, and both recurrences remitted after an additional 3–6 wk of PP. Median observation period was 4.5 yr (0.8–16.3 yr). Complete remission of recurrent FSGS has been sustained in all seven patients, and all patients have stable graft function with recent plasma creatinine <1.5 mg/dL in six of seven patients. Most recent urine protein/creatinine is 0.13–0.61 mg/mg in six of seven patients. One patient has heavy proteinuria secondary to chronic allograft nephropathy 16 yr post‐transplant. Intensive and prolonged PP, when initiated early in the post‐operative period, is effective in treating recurrent FSGS and preventing graft loss without the use of additional immunosuppressants.     

Utility of thrombophilia screening in pediatric renal transplant recipients

Thrombosis after kidney transplantation may result in catastrophic outcomes, including graft loss. Thrombophilia has been implicated in post‐transplant thrombosis; data, however, are inconclusive on the impact of acquired and inherited thrombophilia and resultant thrombosis in renal graft recipients. We aimed to evaluate whether identifying children with thrombophilia during the pretransplant evaluation predicted post‐transplant outcomes. We reviewed 100 kidney transplants performed in 100 children, aged 1‐18 years, in a single‐center retrospective study. Routine pretransplant comprehensive thrombophilia evaluation was completed. Thrombophilia was demonstrated in 36% patients (N = 36). TEs occurred in 11 patients before kidney transplant. Low PS and antithrombin were found in 9/86 (10.5%) and 2/89 (2.2%) children, respectively. Heterozygosity for FLV and PGM were found in 5/81 (6.2%) and 1/93(1.1%) children, respectively. A post‐transplant thrombotic event occurred in 10 children (10%); six involved the renal transplant. The association between a history of a pretransplant thrombotic event and post‐operative renal graft thrombosis approached, but did not reach significance (P = 0.071). There was no association between preoperative screening abnormalities and post‐operative TEs. Graft loss due to a thrombotic event occurred in two patients; none had underlying thrombophilia. Our data suggest that the utility of universal, comprehensive preoperative thrombophilia testing is not beneficial in determining risk of post‐operative graft thrombosis. Thrombophilia testing may be considered in a select population with a history of pretransplant thrombotic event.     

Prelisting predictions of early postoperative survival in infant heart transplantation using classification and regression tree analysis

Infants listed for heart transplantation experience high waitlist and early post‐transplant mortality, and thus, optimal allocation of scarce donor organs is required. Unfortunately, the creation and validation of multivariable regression models to identify risk factors and generate individual‐level predictions are challenging. We sought to explore the use of data mining methods to generate a prediction model. CART analysis was used to create a model which, at the time of listing, would predict which infants listed for heart transplantation would survive at least 3 months post‐transplantation. A total of 48 infants were included; 13 died while waiting, and six died within 3 months of heart transplant. CART analysis identified RRT, blood urea nitrogen, and hematocrit as terminal nodes with alanine transaminase as an intermediate node predicting death. No patients listed on RRT (n = 10) survived and only three of 12 (25%) patients listed on ECLS survived >3 months post‐transplant. CART analysis overall accuracy was 83%, with sensitivity of 95% and specificity 76%. This study shows that CART analysis can be used to generate accurate prediction models in small patient populations. Model validation will be necessary before incorporation into decision‐making algorithms used to determine transplant candidacy.     

Perioperative renal transplantation management in small children using adult‐sized living or deceased donor kidneys: A single‐center experience

Kidney transplantation remains the treatment of choice for children with ESRD. Optimal perioperative management is critical in small recipients of ASK to assure adequate graft perfusion. We present a single‐center experience outlining management for patients weighing <20 kg who underwent primary renal transplantation with ASKs between 2007 and 2016. Sixty‐three patients met study criteria and underwent 34 living‐related, six living‐unrelated, and 23 deceased donor kidney transplants. Median age and weight at transplant were 25 months (IQR 18‐37 months; range 11 months‐6 years) and 11.0 kg (IQR 9.2‐14.5 kg; range 7.1‐19.5 kg). Eighty‐nine percent of patients required vasoactive agents intra‐operatively, with twenty patients requiring prolonged vasoactive agents post‐operatively. Intra‐operatively, patients received 51.9 mL/kg of crystalloid, 27.3 mL/kg of 5% albumin, and 13.6 mL/kg of packed red blood cells. Most (93.7%) patients were extubated on POD#0. Weights peaked on post‐operative days three through five. Over a median follow‐up of 49 months (IQR 31‐86 months; range 0‐130 months), four grafts were lost, two due to thrombosis and two secondary to chronic rejection. There was one patient death six months post‐transplant due to causes unrelated to transplantation. Graft survival at 1, 5, and 10 years was 98.4%, 96.6%, and 84.2%, respectively. Of surviving allografts, the median 1, 5, and 10 years post‐transplant eGFR was 122.9, 90.0, and 59.2 mL/min/1.73 m² as determined by the 2009 Schwartz formula. Renal transplantation in small children using ASKs requires meticulous perioperative management including adequate fluid resuscitation and judicious use of pressors to assure adequate graft perfusion. The use of ASKs from living or deceased donors results in satisfactory short and long‐term outcomes.     

De novo therapy with everolimus and reduced‐exposure cyclosporine following pediatric kidney transplantation: A prospective,multicenter, 12‐month study

Prospective data regarding the de novo use of everolimus following kidney transplantation in children are sparse. In a prospective, 12‐month, single‐arm, open‐label study, pediatric kidney transplant patients received everolimus (target trough concentration ≥3 ng/mL) with reduced‐exposure CsA and corticosteroids, with or without basiliximab induction. Sixteen of the 18 patients completed the study on‐treatment. Age range was 2–16 yr (mean 10.9 yr); eight patients received a living donor graft. Mean (s.d.) everolimus level was 7.4 (3.1) ng/mL during the first 12 months post‐transplant. There were no cases of BPAR, graft loss, or death during the study. Protocol biopsies were performed at month 12 in seven patients, with subclinical (untreated) acute rejection diagnosed in one case. Mean (s.d.) estimated GFR (Schwartz formula) was 98 (34) mL/min/1.73 m² at month 12. Three patients experienced one or more serious adverse events with a suspected relation to study medication. One patient discontinued study medication due to post‐transplant lymphoproliferative disease (5.6%). Everolimus with reduced‐dose CsA and corticosteroids achieved good efficacy and renal function and was well tolerated in this small cohort of pediatric kidney transplant patients. Controlled trials are required to answer remaining questions about the optimal use of everolimus in this setting.     

Reno‐portal anastomosis as an approach to pediatric kidney transplantation in the setting of inferior vena cava thrombosis

In pediatric renal transplantation in the setting of IVC thrombosis, the retrohepatic IVC or gonadal veins are often used for outflow. However, if use of systemic venous outflow is unsuccessful, options become limited. We report the use of the portal vein for venous outflow in kidney retransplantation in the setting of IVC thrombosis. The patient is a 19‐month‐old male who developed end‐stage renal failure at seven months of age secondary to hypotension after spontaneous rupture of an accessory renal vein. The IVC was occluded during emergent laparotomy, and the patient developed extensive IVC thrombosis. The first two transplant attempts used the retrohepatic IVC for venous outflow. Despite good initial flow, in both instances the renal vein thrombosed on post‐operative day 1. In an unsuccessful salvage attempt of the second transplant, a reno‐portal anastomosis was performed. With few options for vascular access, a third transplant was attempted. The reno‐portal stump from the second transplant was used for outflow. The patient recovered well from his third transplant (creatinine 0.6 mg/dL 35 months post‐surgery), demonstrating that the portal vein can be used for outflow in cases of extensive IVC thrombosis.     

The effect of transfer to adult transplant care on kidney function and immunosuppressant drug level variability in pediatric kidney transplant recipients

Adolescent age at time of transplant has been recognized as a risk factor for renal allograft loss. Increased risk for graft failure may persist from adolescence to young adulthood. Transfer of care is hypothesized as a risk factor for non‐adherence and graft loss. We explored whether kidney allograft function declined at an accelerated rate after transfer of care to adult transplant centers and whether coefficient of variation of tacrolimus (CV TAC) trough levels predicted allograft loss. Single‐center, retrospective chart review was performed for pediatric kidney transplant recipients who received transplants between 1999 and 2011. Change in eGFR pre‐ and post‐transfer was performed via a linear mixed‐effects model. CV TAC was calculated in transplant recipients with TAC data pre‐ and post‐transfer. t test was performed to determine the difference between means of CV TAC in subjects with and without allograft loss following transfer of care. Of the 138 subjects who transferred to adult care, 47 subjects with data pre‐ and post‐transfer demonstrated a decrease in the rate of eGFR decline post‐transfer from 8.0 mL/min/1.73 m² per year to 2.1 mL/min/1.73 m² per year, an ~80% decrease in eGFR decline post‐transfer (P = 0.01). Twenty‐four subjects had CV TAC data pre‐ and post‐transfer of care. Pretransfer CV TAC for subjects with allograft loss post‐transfer was significantly higher than in subjects without allograft loss (49% vs 26%, P < 0.05). Transfer of care was not independently associated with acceleration in eGFR decline. CV TAC may aid in identifying patients at risk for allograft loss post‐transfer.     

Is there an optimal organ acceptance rate for pediatric heart transplantation: “A sweet spot”?

Despite a limited supply of donors, potential donor hearts are often declined for subjective concerns regarding organ quality. This analysis will investigate the relationship between donor heart AR and patient outcome at pediatric transplant centers. The UNOS database was used to identify all match runs for pediatric candidates (age < 18 years) from 2008 through March 2015 in which a heart offer was ultimately placed. Centers which received ≥10 offers/y were included (10 634 offers, 38 centers). Transplant centers were stratified based on their AR: low (<20%, n = 13), medium (20%‐40%, n = 16), or high (>40%, n = 9). Low AR centers experienced worse negative WL outcome compared with medium (P = .022) and high (P = .004) AR centers. Low AR centers had similar post‐transplant graft survival to medium (P = .311) or high (P = .393) AR centers; however, medium AR centers had better post‐transplant graft survival than high AR centers (P = .037). E‐F survival from listing regardless of transplant was worse for low AR centers compared with medium (P < .001) or high (P = .001) AR centers. Low AR centers experience worse WL outcomes without improvement in post‐transplant outcomes. High AR centers experience higher post‐transplant graft failure than medium AR centers. AR of 20%‐40% appears to have optimal WL and post‐transplant outcomes.     

Everolimus and reduced calcineurin inhibitor therapy in pediatric liver transplant recipients: Results from a multicenter,prospective study

In a 24‐month, multicenter, single‐arm, prospective study, 56 pediatric liver transplant patients with or without basiliximab induction were converted at 1‐6 months post‐transplant from standard calcineurin inhibitor (CN) therapy (± mycophenolic acid), to everolimus with reduced exposure to CNI (tacrolimus n=50, cyclosporine n=6). Steroid therapy was optional. Recruitment was stopped prematurely due to high rates of PTLD, treatment‐related serious infections leading to hospitalization and premature study drug discontinuation. Subsequently, patients aged <7 years reverted to local standard‐of‐care immunosuppression. Mean tacrolimus concentration was above or near the upper end of the maintenance target range (2‐5 ng/mL) until after month 6 post‐enrollment. The primary variable, mean (SD) change in eGFR from baseline to month 12 (last observation carried forward), was +6.2 (19.5) mL/min/1.73 m². Two patients experienced treated biopsy‐proven acute rejection. No graft losses or deaths occurred. PTLD occurred in five patients (8.9%) (3/25 [12.0%] patients <2 years, 2/31 aged 2‐18 years [6.5%]). Adverse events, serious adverse events, and discontinuation due to adverse events were reported in 100.0%, 76.8%, and 44.6% of patients, respectively. In conclusion, everolimus with reduced CNI improved renal function while maintaining antirejection potency in pediatric liver transplant patients but safety outcomes suggest that patients were overimmunosuppressed.     

Lymphocele after pediatric kidney transplantation: Incidence and risk factors

Lymphocele is a well‐known postoperative complication after kidney transplantation. The aim of this study was to analyze time trend incidence, risk factors, and outcome of post‐transplant lymphocele in a large pediatric cohort. This is a retrospective single institution review of 241 pediatric kidney transplants performed from 2000 to 2013. Etiology of end‐stage renal disease, recipient age and gender, transplant year, BMI percentile for age, type of dialysis, living/non‐living related donor, acute rejection, and multiple transplantations were analyzed in association with lymphocele formation. Fourteen of 241 (5.81%) children developed a postoperative lymphocele. There has been a reduction in the incidence of lymphocele after 2006 (3.22% vs. 8.55%, p < 0.05). Significant risk factors for lymphocele were older age (≥11 yr), transplant before 2006, male gender, BMI percentile for age ≥95%, and multiple transplantations (p < 0.05). The one‐yr graft survival was significantly reduced in the group with lymphocele compared with control (81.2% vs. 92.51%, p < 0.04). This is the first pediatric report showing the following risk factors associated with post‐transplant lymphocele: age ≥11 yr, male gender, BMI for age ≥95%, and multiple transplantations. A lymphocele can contribute to graft loss in the first‐year post‐transplant.     

Heart transplantation in an infant with Williams‐Beuren syndrome and rapidly progressive ischemic cardiomyopathy

Ischemic cardiomyopathy with resultant refractory HF may occur in patients with WBS, often as the result of coronary involvement with SVAS. The rapid development of arteriopathy at a young age raises concerns regarding transplant candidacy due to progressive stenoses at other arterial sites with potential detrimental impact on long‐term heart graft function. We report a 2‐month‐old male infant diagnosed with mild aortic stenosis during the neonatal period, but subsequently developed rapidly progressive supravalvar and coronary artery stenoses leading to cardiogenic shock due to myocardial ischemia. The presentation led to the diagnosis of WBS. He required prolonged CPR including ECMO therapy. He subsequently underwent LVAD implantation as bridge to transplant and 4 days later heart transplantation. His post‐operative course was complicated by prolonged mechanical ventilation and extended intensive care unit and hospital stays. However, at follow‐up 18 months post‐transplant he continues to have normal graft function with mild, non‐progressive residual coarctation of aorta and non‐progressive moderately hypoplastic pulmonary arteries.     

Tacrolimus therapeutic drug monitoring and pediatric renal transplant graft outcomes

Predose monitoring of tacrolimus levels is standard practice in the care of pediatric renal transplant patients. This is despite a paucity of data investigating the ideal target range in children, and controversy as to whether tacrolimus levels correlate with renal transplant outcomes. We performed a retrospective cohort analysis of 48 renal transplant patients at a single Canadian pediatric transplant center following the initiation of a tacrolimus–mycophenolate–prednisone‐based IS protocol. We analyzed the relationship of graft function, as defined by GFR up to five yr post‐transplant, to the preceding mean tacrolimus level. There was no significant correlation between absolute GFR and mean tacrolimus levels (r = 0.206, p = 0.38). However, a higher mean tacrolimus level, particularly ≥10 ng/mL in the first three months after transplantation, was associated with a slower rate of decline in GFR with time (r = 0.608, p = 0.004) and with a less likelihood of developing CKD five yr after transplant. We suggest that the optimal target range for tacrolimus levels may be at the upper end of what is currently practiced and that further research to validate these findings would be useful.     

Efficacy and safety of conversion of mycophenolate mofetil to enteric‐coated mycophenolate sodium in Mexican renal transplant children

Reyes H, Hernández AM, Valverde S, Cataneo A, Mendoza A, Barrera I, Ortíz L, García‐Roca P, Lopéz‐Martínez B, Castañeda‐Hernández G, Medeiros M. Efficacy and safety of conversion of mycophenolate mofetil to enteric‐coated mycophenolate sodium in Mexican renal transplant children.
Pediatr Transplantation 2010: 14:746–752. © 2010 John Wiley & Sons A/S. Abstract: The aim of the study was to evaluate the efficacy and safety of the conversion of MMF to EC‐MPS in pediatric renal transplant recipients. We included 12 patients with stable graft function who were receiving MMF treatment. In the first visit, a complete medical examination was performed, which included a GSRS, a nine‐point pharmacokinetic profile, samples for renal, liver and hematological tests and evaluation of IMPDH2 gene expression. The patients were transferred to an equimolar dose of EC‐MPS. Two wk later, a clinical evaluation and blood collection, as in the first visit were performed. There was no change in serum creatinine, leukocyte count, serum albumin, or transaminase levels, but we found a statistically significant reduction of hemoglobin after conversion (13.2 ± 1.6 g/dL with MMF vs. 12.5 ± 1.3 g/dL when receiving EC‐MPS). The GSRS total mean score was 16 ± 12 with MMF vs. 8 ± 5 with EC‐MPA (p < 0.05). There was no statistically significant difference between formulations in the gene expression of IMPDH 2, in the AUC_0‐12h or in C_max. However, peak concentration occurred later with EC‐MPS.     

Outcomes of kidney transplants in pediatric patients with the vertebral defects,anal atresia,cardiac defects,tracheoesophageal fistula,renal anomalies,limb abnormalities association

In this single‐center retrospective study, we analyzed kidney transplant outcomes in nine pediatric patients with VACTERL [vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities] association—making this the largest study of its kind. Of 743 pediatric kidney transplant recipients at our center (1980‐2017), nine had documented diagnoses of VACTERL association. All nine had congenital anorectal malformations and renal anomalies, five had vertebral defects, and one had a bifid thumb and tracheoesophageal fistula. Renal anomalies included dysplasia (n = 6), aplasia (n = 3), and horseshoe kidney (n = 2). Congenital lower urinary tract anomalies included neurogenic bladder (n = 6), obstructive uropathy (n = 4), anovesicular fistula (n = 1), rectourethral fistula (n = 1), and posterior urethral valves (n = 1). Age at transplant ranged from 1.2 to 15 years (mean, 7.3; standard deviation [SD], 5.5); 6 (67%) were male, and 3 (33%) were female; 6 (67%) had a living related donor, and 3 (33%) had a deceased donor. The overall graft survival rate was 78% (range, 1.5 to 25.2 years; mean, 10.5; SD, 8.9). One month post‐transplant, one recipient died with a functioning graft. At 3.7 years post‐transplant, one graft failed because of recurrent pyelonephritis. Post‐transplant urologic complications included pyelonephritis (n = 6), vesicoureteral reflux (n = 5), and graft hydronephrosis (n = 4). We conclude that pediatric patients with VACTERL association can be safely transplanted—careful patient selection with vigilance and intervention for pre‐ and post‐transplant urologic complications is essential.