Standardizing resistive indices in healthy pediatric transplant recipients of adult-sized kidneys

Gholami S, Sarwal MM, Naesens M, Ringertz HG, Barth RA, Balise RR, Salvatierra O. Standardizing resistive indices in healthy pediatric transplant recipients of adult-sized kidneys.
Pediatr Transplantation 2010: 14: 126–131. © 2009 John Wiley & Sons A/S.
Abstract:  Small pediatric recipients of an adult-sized kidney have insufficient renal blood flow early after transplantation, with secondary chronic hypoperfusion and irreversible histological damage of the tubulo-interstitial compartment. It is unknown whether this is reflected by renal resistive indices. We measured renal graft resistive indices and volumes of 47 healthy pediatric kidney transplant recipients of an adult-sized kidney in a prospective study for six months post-transplant. A total of 205 measurements were performed. The smallest recipients (BSA ≤0.75 m²) had higher resistive indices compared to recipients with a BSA between 0.75 and 1.5 m² (p < 0.0001) and to recipients with a BSA ≥ 1.5 m² (p < 0.0001). Resistive indices increased during the first six months in the smallest recipients (p = 0.02), but not in the two larger recipient groups (BSA 0.75–1.5 m² and ≥1.5 m²). All three BSA groups showed a reduction in renal volume after transplantation, with the greatest reduction occurring in the smallest recipients. In conclusion, renal transplant resistive indices reflect pediatric recipient BSA dependency. The higher resistance to intra-renal vascular flow and significant decrease in renal volume in the smallest group likely reflect accommodation of the size discrepant transplanted adult-sized kidney to the smaller pediatric recipient vasculature with associated lower renal artery flow.     

The relationship of donor source and age on short- and long-term allograft survival in pediatric renal transplantation

Abstract:  Limited pediatric data on allograft survival from advanced aged kidney donors exist. To determine the influence of donor source and age on allograft survival in pediatric renal transplant recipients, we analyzed the OPTN database. Allograft survival for 7291 pediatric renal transplants was evaluated. Up to five yr post-transplantation, graft survival was higher for LD vs. DD recipients. At seven yr, allograft survival was 71% in 18–54 yr-old LD recipients, 59.1% in ≥55 yr-old LD, and 45.1% in ≥50 yr-old DD recipients. An approximate 35% improvement in allograft survival in 18–54 yr-old LD recipients was observed. Multivariate results showed that recipients of LD 35–49 (aRR 0.66, 95% CI 0.55–0.80) and LD 50–54 (aRR 0.65, 95% CI 0.45–0.94) have a graft survival advantage over the ideal DD. In LD ≥55 yr, no improvement in graft survival was observed when compared with the 18–34 yr-old DD. In summary, we observed in a pediatric population, <55 yr-old LD kidneys afford improved long-term allograft survival when compared with DD kidney recipients. Increasing awareness of the long-term graft survival advantage for children receiving an LD kidney, even from older donors, should be a priority.     

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.     

Urological complications,vesicoureteral reflux,and long‐term graft survival rate after pediatric kidney transplantation

To describe a single‐center experience with kidney transplantation and then study some donor and recipient features that may impact on graft survival and urological complication rates. We reviewed our database searching for pediatric patients who underwent kidney transplantation from August 1985 through November 2012. Preoperative data and postoperative complications were recorded. Graft survival rates were analyzed and compared based on the type of donor, donor's age from deceased donors, and recipients' ESRD cause. Kaplan–Meier curves with log rank and Wilcoxon tests were used to perform the comparisons. There were 305 pediatric kidney transplants. The mean recipient's age was 11.7 yr. The mean follow‐up was 11.0 yr. Arterial and venous thrombosis rates were 1.6% and 2.3%, respectively, while urinary fistula and symptomatic vesicoureteral reflux were diagnosed in 2.9% and 3.6% of cases, respectively. Deceased kidney transplantation had a lower graft survival rate than living kidney transplantation (log rank, p = 0.005). Donor's age (p = 0.420) and ESRD cause (p = 0.679) were not significantly related to graft survival rate. In long‐term follow‐up, type of donor, but not donor's age, impacts on graft survival rate. ESRD cause has no impact on graft survival rate, showing that well‐evaluated recipients may have good outcomes.     

Safety and pharmacokinetics of daclizumab in pediatric renal transplant recipients

Abstract:  This study examined the safety and pharmacokinetics/pharmacodynamics of daclizumab in combination with mycophenolate mofetil (or azathioprine), corticosteroids, and cyclosporine or tacrolimus, in 61 pediatric renal allograft recipients in three age groups: less than or equal to five yr (n = 18), 6–12 yr (n = 18), and 13–17 yr (n = 25). The dosing regimen was daclizumab 1.0 mg/kg before transplantation, followed by four biweekly doses. The pharmacokinetics of daclizumab were described using NONMEM software. Median (range) estimated trough daclizumab levels achieved on day 56 (before dose 5) were 3.88 μg/mL (2.48–8.78), 4.54 μg/mL (1.79–18.7), and 4.94 μg/mL (0.05–10.6) in the less than or equal to five yr (n = 15), 6–12 yr (n = 17), and 13–17 yr (n = 22) age groups, respectively. Steady-state median (range) daclizumab exposures were 2040 mg · h/mL (1585–3778), 2757 mg · h/mL (1873–3494) and 3297 mg · h/mL (1705–6453), respectively. Saturation of the IL-2R occurred rapidly and was maintained for greater than or equal to three months after transplantation. Daclizumab was generally well-tolerated with no acute allergic or anaphylactic reactions, deaths or malignancies during the study. The proportion of patients who developed acute rejection at six and 12 months was 8.5% and 16.7%, respectively. This study shows that adding daclizumab at 1 mg/kg to standard immunosuppressive therapy provides safe and effective IL-2R blockade.     

Outcome of living donor renal allograft survival in children with focal segmental glomerulosclerosis

Abstract:  FSGS is the most frequent GN that may recur in a renal allograft. Compared with adults, the impact of FSGS on graft survival appears to be more significant in children. Thus we decided to assess graft survival and complications after renal transplantation in children with FSGS. Outcome of renal transplantation in 25 children with FSGS who received a renal transplant at Labafi Nejad Hospital was studied and compared with 75 patients as a control group. The mean follow-up duration was 68.16 (s.d. = 41.93) months. Other than demographics, variables such as DGF, acute rejection, number of acute rejection episodes, and graft failure in both groups were evaluated. Acute rejection was seen in 22/25 (88%) of FSGS group, compared to 40/75 (53.3%) in the control group. This difference was statistically significant (p = 0.001). DGF was seen in 4/25 (16%) and 13/75 (17.3%) in the FSGS and control groups, respectively (p = N.S.). The mean graft survival time was 115.61 (s.e.m. = 12.56) and 155.56 (s.e.m. = 7.16) month in FSGS and control group, respectively (p = N.S.). We demonstrated that graft function and survival were not significantly different in the FSGS and control patients. However, acute rejection episodes were more common in FSGS patients but without a significant impact on graft survival.     

Outcome of kidney transplantation in Canadian Aboriginal children in the province of British Columbia

Abstract:  Renal transplantation remains the therapy of choice for children and adolescents with ESRD. Differences in graft survival are observed in kidney transplant recipients of different race and ethnicities. Data in pediatric populations are limited and confounded by disparities in access to health care. We performed a retrospective single Canadian centre database review to determine the short- and long-term outcomes of kidney transplantation in Aboriginal children compared to non-Aboriginals. A total of 159 primary renal transplant recipients at BCCH between 1985 and 2005 were examined (15% Aboriginal). Aboriginal children had different etiologies of ESRD, and a higher percentage of females, but were similar in age at transplantation, cold ischemia time and living donation rate. Early graft outcomes such as delayed graft function, episodes of acute rejection in the first year post-transplant and estimated glomerular function rate at one yr were similar in both groups. Long-term graft survival, however, was significantly worse in the Aboriginal group, with a significantly increased rate of late rejections: 50% compared with 26.7% among non-Aboriginals (p = 0.03). In a province with uniform access to health care, significant differences in long-term graft outcome exist among Aboriginal children compared with non-Aboriginals.     

Demographics and response to therapeutic plasma exchange in pediatric renal transplantation for focal glomerulosclerosis: a single center experience

Abstract:  Recurrence of FSGS following renal transplantation in pediatric patients is reported as 20–57%. Records of 37 pediatric patients transplanted for FSGS between 1990 and 2005 at a single center were reviewed. Recurrence of disease was assessed by nephrotic range proteinuria and/or FSGS on biopsy. Response to TPE was defined as urine protein to creatinine ratio <0.2. Forty-nine percent of patients were African American, 38% were Caucasian. Fifty-four percent received kidneys from deceased donors and 46% from live donors. Seven patients received preemptive TPE prior to transplantation. Two of these seven patients recurred in the transplanted kidney (28%). Recurrent FSGS occurred in 16 of 37 patients (46%), all of whom received TPE. Recurrence occurred within one month in 12 of 37 patients (32%); eight remitted with TPE (67%). Four of 12 patients failed to respond to TPE. Four of 37 patients (14%) recurred more than one month after transplantation and underwent TPE; three-fourths of patients remitted (75%). Twenty-one of 37 patients (54%) did not recur. One and five yr graft survivals were 84% and 67%, respectively. Median graft survival was 6.7 yr (5.2–10.3). Despite recurrence, FSGS patients can achieve sustained graft function.     

Acute rejection episodes in pediatric renal transplant recipients with cytomegalovirus infection

Abstract:  CMV infection is the most important opportunistic virus infection after renal transplantation leading to increased patient mortality, graft loss, risk for acute rejection episodes and impaired renal function. The potential impact of prophylactic anti-viral therapy on long-term graft outcome is relevant. The aim of this study was to evaluate the incidence of CMV infection, its risk factors and long-term outcome in children after renal transplantation. 103 children (mean age 10.6 ± 5.3, range 1.6–22.0 yr) were monitored weekly for pp65 for the first 6–8 wk after renal transplantation, followed by a monthly monitoring for the first year. CMV infection occurred in 23/103 children (21.1%) with 10 patients (9.7%) developing CMV disease characterized by positive pp65 in the presence of organ involvement. The CMV R−/D+ and R+/D+ serostatus was significantly associated with an increased risk of CMV infection (p < 0.0001 and p = 0.009). 14/28 R−/D+ patients developed CMV infection despite prophylactic treatment with CMV hyperimmune globulin. The incidence of acute rejection episodes after or during CMV infection was significantly increased (p = 0.003) and the D+ serostatus was significantly associated with acute rejection episodes within the first year after transplantation (p = 0.006). In summary the overall incidence of CMV infection in this single center experience is 21.1%. The D+ serostatus represents a serious risk factor for both CMV infection and acute rejection episodes. In future the potential impact of different modalities of prophylactic anti-viral therapy on the prevention of acute rejection should be considered.     

Hyponatremia increases mortality in pediatric patients listed for liver transplantation

Carey RG, Bucuvalas JC, Balistreri WF, Nick TG, Ryckman FR, Yazigi N. Hyponatremia increases mortality in pediatric patients listed for liver transplantation.
Pediatr Transplantation 2010: 14: 115–120. © 2009 John Wiley & Sons A/S.
Abstract:  To evaluate hyponatremia as an independent predictor of mortality in pediatric patients with end-stage liver disease listed for transplantation. We performed a single-center retrospective study of children listed for liver transplantation. We defined hyponatremia as a serum sodium concentration <130 mEq/L that persisted for at least seven days. The primary outcome was death on the waiting list. Ninety-four patients were eligible for the study. The prevalence of hyponatremia was 26%. Kaplan–Meier survival analysis demonstrated that patients with hyponatremia had decreased pretransplant survival compared with patients who maintained a serum sodium >130 mEq/L (p < 0.001). Univariable association analyses demonstrated death on the waiting list was also associated with higher median PELD scores at listing (p = 0.01), non-white race (p = 0.02), and age <1 yr (p = 0.001). Logistic regression analysis identified hyponatremia and non-white race as independently associated with pretransplant mortality [OR = 8.0 (95% CI: 1.4–45.7), p = 0.02 and OR = 6.3 (95% CI: 1.25–33.3), p = 0.03]. When hyponatremia was added to the PELD score, it was significantly better in predicting mortality than the PELD score alone ( c -statistic = 0.79, p = 0.03). Hyponatremia identifies a subset of pediatric patients with increased risk of pretransplant mortality and improves the predictive ability of the current PELD score.     

Improved outcome of pediatric kidney transplantations in the Netherlands – Effect of the introduction of mycophenolate mofetil?

Collaboration of the Dutch centers for kidney transplantation in children started in 1997 with a shared immunosuppressive protocol, aimed at improving graft survival by diminishing the incidence of acute rejections. This study compares the results of transplantations in these patients to those in a historical reference group. Ninety-six consecutive patients receiving a first kidney transplant were treated with an immunosuppressive regimen consisting of mycophenolate mofetil, cyclosporine and corticosteroids. The results were compared with those of historic controls (first transplants between 1985 and 1995, n = 207), treated with different combinations of corticosteroids, cyclosporine A and/or azathioprine. Cytomegalovirus (CMV) prophylaxis was prescribed to high-risk patients in the study group, and only a small proportion of the reference group. The graft survival at 1 yr improved significantly: 92% in the study group, vs. 73% in the reference group (p < 0.001). In the study group 63% of patients remained rejection-free during the first year; in the reference group 28% (p < 0.001). After statistical adjustment of differences in baseline data, as cold ischemia time, the proportion of LRD, preemptive transplantation, and young donors, the difference between study and reference group in graft survival (RR 0.33, p = 0.003) and incidence of acute rejection (RR 0.37, p < 0.001), as the only factor, remained statistically significant, indicating the effect of the immunosuppressive therapy. In the first year one case of malignancy occurred in each group. CMV disease occurred less frequently in the study group (11%) than in the reference group (26%, p = 0.02). As a new complication in 4 patients bronchiectasis was diagnosed. A new consensus protocol, including the introduction of mycophenolate mofetil, considerably improved the outcome of pediatric kidney transplantation in the Netherlands, measured as reduction of the incidence of acute rejection and improved graft survival.     

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.     

Survival among children with portal vein thrombosis and end-stage liver disease

Al-Holou S, Mathur AK, Ranney D, Kubus J, Englesbe MJ. Survival among children with portal vein thrombosis and end-stage liver disease.
Pediatr Transplantation 2010: 14: 132–137. © 2009 John Wiley & Sons A/S.
Abstract:  Occlusive PVT concurrent with chronic liver disease is a common clinical entity among pediatric patients referred for transplantation. The natural history of PVT is unknown. Our aim was to determine, using a retrospective cohort design, if children under 13 yr with chronic liver disease and concomitant PVT have an increased mortality risk prior to and after transplantation. A total of 203 patients were included in the study. Nearly 10% of the population had PVT (n = 19); 63.2% of PVT patients (5.9% of total cohort) underwent liver transplantation (n = 12). PVT patients tended to be younger than non-PVT patients at evaluation (1.94 ± 3.51 vs. 3.79 ± 4.11, p = 0.059). Clinical and demographic factors were similar between the two groups. Regarding survival, four PVT patients died, of which two had undergone transplantation. Kaplan–Meier analyses indicated that PVT and non-PVT patients had similar survival from the time of evaluation, on the waiting list, and after transplant. Although limited by sample size, our study suggests that a diagnosis of PVT does not increase the mortality risk for children waiting for a liver transplant. Further study is needed to discern variations in mortality risk that may occur in the pediatric chronic liver disease population with PVT.     

Incidence,impact, and treatment of portal and hepatic venous complications following pediatric liver transplantation: A single‐center 12 year experience

Heffron TG, Pillen T, Smallwood G, Henry S, Sekar S, Casper K, Solis D, Tang W, Fasola C, Romero R. Incidence, impact, and treatment of portal and hepatic venous complications following pediatric liver transplantation: A single‐center 12 year experience.
Pediatr Transplantation 2010: 14:722–729. © 2010 John Wiley & Sons A/S. Abstract: PVT or PVS and HVOO are known causes of graft and patient loss after pediatric liver transplantation. Increased incidences of these complications have been reported in partial livers including DDSLT or LDLT. From 1997 to 2008, 241 consecutive pediatric patients received 271 hepatic grafts at a single center. Median follow‐up is 1856 days. Surgical technique, demographics, lab values, and radiologic imaging procedures were obtained utilizing OTTR^® to evaluate the relationship of portal and hepatic complications with risk factors, patient and graft survival. Grafts were composed of 115/271 (42.4%) partial livers of which 90 (33.2%) were DDSLT and 25 (9.2%) LDLT. Of 271 patients, 156 (57.6%) received whole‐sized grafts. There were six PVC in five patients with one patient requiring retransplantation (0.34%) and no patient deaths. Utilizing all three hepatic vein orifices on the recipient hepatic vena cava and the donor hepatic vein cut short enables a wide hepatic outflow tract unlikely to twist. None of the 241 patients developed early or late complications of the hepatic vein. None of the last 128 consecutive patients who received 144 grafts over seven and a half yr have developed either early or late complications of the hepatic or portal vein. Partial‐graft actuarial survival was similar to whole‐graft survival (87.2% vs. 85.3% at one yr; 76.6% vs. 80.2 at three yr; p = 0.488). Likewise, patient survival was similar between partial grafts and whole grafts (93.8% vs. 93.1% at one yr; 89.8% vs. 87.2% at three yr; p = 0.688) with median follow‐up of 1822 (±1334) days. Patients receiving partial livers were significantly younger and smaller than patients receiving whole livers (p < 0.001). Portal and hepatic venous complications may have negative effects on patient or graft survival after pediatric liver transplantation. In our series, there was one graft and no patient loss related to portal or hepatic venous complications after pediatric liver transplantation over 12 yr.     

Short‐term and long‐term effects of slow graft function on graft survival in pediatric live donor renal transplantation

Otukesh H, Hosein R, Fereshtehnejad S‐M, Riahifard A, Basiri A, Simforoosh N, Chalian M, Jazayeri S, Chalian H, Safarzadeh AE, Sharifian M, Hoseini S. Short‐term and long‐term effects of slow graft function on graft survival in pediatric live donor renal transplantation. Pediatr Transplantation 2010:14:196–202. © 2009 John Wiley & Sons A/S. Abstract: SGF generally has early and long‐term consequences for allograft survival. Limited studies have been performed on SGF and its complications in pediatric renal transplantation. Therefore, 230 children who received transplants between 1985 and 2005 in Labafi Nejad hospital were included in this study. SGF was defined if the serum creatinine level increased, remained unchanged, or decreased by <10% per day immediately after surgery during three consecutive days in the first week after transplantation. The children were divided into two groups: 183 children in group A (non‐SGF) and 47 patients in group B (SGF). The impact of SGF on renal function within the first year, long‐term graft survival and post‐transplantation complications were analyzed and compared using logistic regression model and Kaplan–Meier survival analysis. The incidence of graft failure at the end of follow‐up period was significantly more common in SGF group (53.2% vs. 22.4%, p < 0.001). The median survival time was 140.25 (s.e.m. = 19.35) months in group A (non‐SGF) and 60 (s.e.m. = 17.90) months in group B (SGF) (p < 0.001). The graft survival rate was 94.9%, 91.9%, 83.9%, 79.2%, and 72% at one, three, five, seven, and twelve yr after transplantation in children without SGF vs. 75.6%, 53.2%, 47.2%, 40% at one, three, five, and seven yr after transplantation in patients with SGF. The results of our study showed that slow graft function could remarkably affect graft survival and worsen both short‐term and long‐term transplantation outcomes. Thus, the prevention of SGF is one of the most important issues in graft survival improvement.     

Multicenter trial of everolimus in pediatric renal transplant recipients: results at three year

Abstract:  There are few prospective clinical trials of mTOR inhibitors (or proliferation signal inhibitors) combined with CNI inhibitors in de novo pediatric renal transplantation. Results reported here are from a multicenter, open-label study in de novo pediatric renal transplant patients (≤16 yr), in which patients received everolimus with cyclosporine and corticosteroids for one yr, then entered an extension study for a further two yr. Nineteen patients completed the one-yr study, of whom three discontinued study medication. Fifteen of the remaining 16 patients entered the extension study, eight of whom were aged <10 yr (Group 1) and seven were aged 10–16 yr (Group 2). Mean daily dose of everolimus during the first 36 months was 1.53 mg/m² BSA. Biopsy-proven acute rejection occurred in three patients in Group 2 and in one patient in Group 1. Biopsy-proven chronic allograft rejection was reported in four patients (two in each age group). Graft survival at one yr was 100%; one patient in Group 2 lost their graft subsequently during the extension. For patients entering the extension, patient survival at three yr was 100%. There were three cases of viral infection, including one case of cytomegalovirus infection. At three yr, mean total cholesterol was 5.5 ± 0.8 m m /L (213 ± 31 mg/dL) and four patients received statin therapy. Mean serum creatinine at 36 months was 96 ± 36 μ m /L (1.1 ± 0.4 mg/dL). This is the first long-term prospective study to demonstrate that a regimen of everolimus, cyclosporine, and corticosteroids provides good efficacy, tolerability, and safety in de novo pediatric renal transplant patients.     

Standard dosing of tacrolimus leads to overexposure in pediatric renal transplantation recipients

Abstract:  Tacrolimus dosage in pediatric RTRs is empirically based on weight. There is evidence that adolescents are at greater risk of toxicity than young children on this dosing regimen. We investigated the rate of tacrolimus overexposure within the first three wk post-transplantation in pediatric RTRs receiving tacrolimus 0.15 mg/kg twice daily. Of 63 RTRs studied, 41 (65.1%) experienced a tacrolimus level above the therapeutic range (supratherapeutic), the majority (48.8%) on days two to four post-transplant. Patients with supratherapeutic levels were older (14.2 vs. 9.9 yr, p = 0.016), taller (146.7 vs. 126.5 cm, p = 0.029), larger (1.36 vs. 1.01 m², p = 0.039) and heavier (44.1 vs. 29.3 kg, p = 0.043) and by day 12 were receiving much lower tacrolimus doses than those without supratherapeutic levels (0.425 vs. 0.198 mg/kg/day, p = 0.0002). Supratherapeutic levels were more common among white (British) children than other ethnic groups (74 vs. 45%, p = 0.02). There were no observed differences in rates of patient or graft survival, or acute rejection during the three-yr study period. Adolescent patients appear to be at greater risk of excessive tacrolimus dosing on a standard regimen. We therefore outline a regimen restricting tacrolimus dosage given to larger/older patients, but emphasize the need for a prospective randomized trial to define optimal dosing.     

G protein beta3 subunit 825T genotype is not associated with differing outcome in pediatric renal transplant recipients

Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta3 subunit of heterotrimeric G proteins (GNB3), associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. The donor GNB3 825TT genotype was associated with reduced kidney allograft survival in adults. We examined (in 100 Caucasian pediatric renal transplant recipients) whether the GNB3 (C825T) polymorphism was associated with disease progression and outcome after renal transplantation. The slope of 1/creatinine was determined by linear regression analysis of a median of 12 points before and after renal transplantation, and the population was divided into two groups of equal size, before and after transplantation, according to the slope. The observed frequencies were 57 for the CC, 33 for the CT, and 10 for the TT haplotype. For comparison, 738 consecutive newborn babies with the same ethnic background were typed in the same hospital. Allele frequencies were statistically not significantly different (chi-square test, p = 0.1327). When dividing the pediatric renal transplant recipients into two groups with regard to the slope of 1/creatinine, both before and after renal transplantation, the observed proportions were CC 26, CT 17, and TT 7 in the group with the poorer slope and CC 31, CT 16, and TT 3 in the group with the better slope before renal transplantation (not significant [NS], chi-square test, p = 0.1777). The observed proportions after renal transplantation were CC 26, CT 16, and TT 8 in the group with the poorer slope and CC 31, CT 15, and TT 4 in the group with the better slope, respectively (NS, chi-square test, p = 0.167). Allograft survival was not associated with the T allele. In conclusion, in a sizeable number of pediatric renal transplant recipients the GNB3 C825T polymorphism was found not to be a genetic risk factor for end-stage kidney disease. In addition, kidney graft function and survival was also found not to be associated with a recipient GNB3 C825T polymorphism.     

Outcomes of pediatric living donor kidney transplantation: A single‐center experience

Renal transplantation is the treatment of choice for children with ESRD offering advantages of improved survival, growth potential, cognitive development, and quality of life. The aim of our study was to compare the outcomes of LDKT vs DDKT performed in children at a single center. Retrospective chart review of pediatric patients who underwent kidney transplantation from 2005 to 2014 was performed. Ninety‐one renal transplants were accomplished, and 31 cases (38.27%) were LDKT, and in 96.7% of the cases, the graft was obtained through laparoscopy. Thirty‐four receptors weighted <25 kg. LDKT group had statistically significant lower cold ischemia times than DDKT one. Complication rate was 9.67% for LDKT and 18.33% for DDKT. eGFR was better in LDKT. Patient survival rate was 100% for LDKT and 98.3% for DDKT, and graft survival rate was 96.7% for LDKT and 88.33%‐80% for DDKT at a year and 5 years. Our program of pediatric kidney transplantation has achieved optimal patient and graft survival rates with low rate of complications. Living donor pediatric kidney transplants have higher patient and better graft survival rates than deceased donor kidney transplants.     

Body mass index as a predictor of outcomes among pediatric kidney transplant recipient

Controversies exist regarding the impact of obesity on patients undergoing kidney transplantation. We sought to estimate the association between BMI and patient outcomes (survival and graft function) among pediatric kidney transplant patients in the USA. We conducted a retrospective analysis of the United Network for Organ Sharing database (1987‐2013), which revealed 13 014 pediatric patients (<18 years old) who underwent primary kidney transplantation. Patients were stratified into five BMI categories established by the World Health Organizations according to their Z score, which is based on age, gender and BMI. The ?2, 0, and +2 categories were collapsed and served as the reference group, while the ?3 (thin) and +3 (obese) categories were evaluated for differences in graft and patient survival. The survival rates between these categories were compared using the Kaplan‐Meier estimator. Cox proportional hazards models were constructed to adjust for recipient and donor characteristics to estimate the risk of graft loss and mortality associated with BMI. Logistic regression models were estimated to evaluate whether there was an association between BMI and DGF. There were no differences in overall patient (P=.1655) or graft (P=.1688) survival between the severely thin, normal, and obese patients. Adjusted models also revealed no statistically significant differences in graft or patient survival. There were no differences in the odds of DGF (both unadjusted and adjusted) among the three groups. The prevalence of obesity is increasing among children who present for kidney transplant in the USA. In this national study of pediatric kidney transplant recipients, there was no difference in graft or patient survival and no differences in rates of DGF among obese children compared to normal and underweight children undergoing kidney transplantation.