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The NMDA antagonist dextromethorphan hydrobromide (DM) may be useful in the treatment of opioid dependence, particularly as a means of reducing tolerance to methadone during replacement therapy. As a prelude to clinical efficacy studies, a randomized, double-blind, placebo-controlled study examined the safety of DM in combination with methadone in inpatient, opiate-dependent volunteers. Male participants received daily methadone (50–70 mg/day) and either DM (n=10) or placebo (n=5) during the 12-day active medication phase of the study. DM participants received doses of 120, 240, and 480 mg/day in increasing order (4 days each). DM at high doses caused mild elevations of heart rate, blood pressure, temperature, and plasma bromide. However, none of these effects was clinically significant. DM caused no significant changes in respiration, pupil diameter, or subjective drug effects measured by standard scales. Participants in the DM group reported many more adverse events than did subjects on placebo (173 vs. 21), but these effects were not clinically serious. The most commonly reported side effects were sleepiness and drowsiness. Several participants reported intoxicating effects at the highest dose. Overall, DM was well-tolerated by the methadone-maintained opiate-dependent subjects studied here. These results support the further exploration of DM as an adjunct medication during methadone replacement therapy.

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Growth following renal transplantation in infants, children, and adolescents was evaluated from 20 years of data reported to the registry of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). The analysis of more than 10,000 recipients addressed the following questions: 1. What is the impact of age, pubertal growth, gender, transplant history, donor source and allograft function on growth after transplantation? 2. Has the height Z score at the time of transplantation changed during the past two decades and has this influenced final adult height? 3. To what extent has recombinant human growth hormone (rhGH) been utilized in growth retarded recipients after transplantation and has its use resulted in accelerated post-transplantation growth? 4. Has the use of steroids for maintenance immunosuppression changed over the past 20 years and how have the perturbations of steroid usage influenced post-transplantation growth? 5. Have changes in clinical care resulted in improved final adult height Z score during the past two decades? Only younger children (<6 years) had initial accelerated post-transplantation growth. The mean increment in height during puberty was 18.8 cm (21.7 cm in 4.7 years for boys and 14.3 cm in 4.5 years for girls). Gender, source of donor graft, or number of grafts did not influence growth. Height Z score at transplantation has improved over the past two decades, as has final adult height with each succeeding era. The use of rhGH after transplantation results in a delta Z score of +0.5 standard deviation (SD). Post-transplantation growth improves with steroid avoidance and changes in estimated glomerular filtration rate (eGFR) impact on growth.

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Studies have shown that adult dialysis patients with a failed renal allograft face a greater risk of mortality on dialysis compared with transplant-naïve patients. The outcome of children returning to dialysis after allograft failure has not been previously studied. Using the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry, we studied patients aged 2-21 years who initiated dialysis from 1 January 1992 to 31 December 2007. Of a total of 5,006 patients, 1,031 patients had a prior history of allograft failure and 3,975 did not (transplant-naïve). Demographic characteristics, including age at dialysis initiation, race, dialysis modality, primary renal disease, era of dialysis initiation, height Z score, and weight Z score were significantly different between the groups (p < 0.0001). Survival probability between the transplant-naïve and allograft failure groups was not significantly different (94.3% and 93.7% at 3 years respectively, log-rank p = 0.08). After covariate adjustment, allograft failure was not a significant factor contributing to increased mortality risk on dialysis (HR 0.98, CI 0.64–1.50, p = 0.94) based on Cox regression analysis. Children with failed allografts who return to dialysis are not at greater risk of mortality than their transplant-naïve dialysis counterparts.

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Short-term renal allograft survival in children has improved. It is therefore important to determine the factors leading to long-term graft function. To this end, we evaluated patients in the NAPTRCS registry who were <12 years old when they received their renal transplant between 1987 and 1993. Children with 10 years of post-transplant follow-up were compared to those in whom the transplant failed within 10 years. Children with a failed transplant within 10 years of the surgery tended to be older, female, and non-Caucasian; they also manifested obstructive uropathy less often and had focal segmental glomerulosclerosis more often, and they received more deceased donor kidneys. Children with a failed renal transplant had fewer HLA donor and recipient matches, received pre-transplant dialysis compared to a preemptive transplant, required dialysis in the first week post-transplant, and required more antihypertensives the first month post-transplant. Allograft function was examined at 10 years. Patients with continued allograft function and a serum creatinine ≤2 mg/dl at 10 years tended to be female and younger, received a younger donor kidney, and received a primary transplant. Serum creatinine, estimated glomerular filtration rate, weight Z score at 10 years, azathioprine use at 10 years, and antihypertensive use at transplant significantly predicted allograft function beyond 10 years. Pediatric transplant physicians should optimize the factors associated with improved long-term allograft function.

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Objective

The PedsQL™ (Pediatric Quality of Life Inventory™) is a modular instrument designed to measure health-related quality of life and disease-specific symptoms. The PedsQL™ Cognitive Functioning Scale was developed as a brief generic symptom-specific instrument to measure cognitive functioning. The objective of the present study was to determine the feasibility, reliability, and validity of the PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients.

Methods

The 6-item PedsQL™ Cognitive Functioning Scale and the PedsQL™ 4.0 Generic Core Scales were completed by pediatric liver transplant recipients ages 8–18 years (n = 215) and parents of pediatric liver transplant recipients ages 2–18 years (n = 502). Both patient self-report and parent proxy-report were available for 212 cases. The 72-item Behavior Rating Inventory of Executive Function (BRIEF), a widely validated measure of executive functioning, was completed by 100 parents and 56 teachers on a subset of patients.

Results

The PedsQL™ Cognitive Functioning Scale demonstrated minimal missing responses (0.0%, child report, 0.67%, parent report), achieved excellent reliability (α = 0.88 child report, 0.94 parent report), distinguished between pediatric patients with liver transplants and healthy children supporting discriminant validity, and was significantly correlated with the PedsQL™ 4.0 Generic Core Scales and the BRIEF supporting construct and concurrent validity, respectively. Pediatric liver transplants recipients experienced cognitive functioning comparable to long-term pediatric cancer survivors.

Conclusions

The results demonstrate the feasibility, reliability, discriminant, construct, and concurrent validity of the PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients.

▼  Abstract: 

We conducted a retrospective review of the North American Renal Transplant Cooperative Study (NAPRTCS) Registry transplant and dialysis arms to assess anemia and growth patterns in children who returned to dialysis after a failed renal transplant from January 1, 1992 to February 3, 2004. Of the 1807 potential study subjects, 1451 had transplant removal data (TxIn vs. TxOut) available for analysis. Four hundred and twenty-one of 1451 patients (29%) had a transplant nephrectomy at the time of entry into the NAPRTCS Registry Dialysis arm. Anemia rates steadily decreased from 72.2% at 30 days after dialysis initiation to 59.5% at 12 months after dialysis initiation. Factors associated with anemia at 30 days after dialysis initiation included hemodialysis, lack of Epo use, and patients who comprised earlier study era cohorts. At one yr after return to dialysis, earlier study cohort era was the only factor associated with anemia status. Patients did not demonstrate significant improvement in height SDS over the course of the study (−2.17 at day 30 to −2.32 at 24 months). The high anemia, poor growth, and low recombinant human growth hormone utilization rates in a group of patients followed longitudinally as they transition from renal transplant to dialysis should cause the pediatric nephrology community to reassess the processes in place to provide optimal care to pediatric end-stage renal disease patients.

▼  Abstract: 

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

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Moudgil A, Martz K, Stablein DM, Puliyanda DP. Good outcome of kidney transplants in recipients of young donors: a NAPRTCS data analysis.
Pediatr Transplantation 2011: 15:167–171. © 2010 John Wiley & Sons A/S.

Abstract:  NAPRTCS data were analyzed to assess outcome of TX recipients from YDs (<5 yr) in comparison with IDs (6–35 yr) and ODs (36–55 yr). Of 9854 TX in NAPRTCS (1987–2003), 469 were YD. Patient survival (PS) and graft survival (GS) were compared between DD TX after 1995; 81YD, 1324 ID, and 429 OD and eGFR were compared among functioning grafts (YD 31, ID 439, OD 174) at three yr. PS was comparable in all groups; GS at one, two, and three yr in TX of YD (91.1%, 83.8%, 79.7%), ID (93.5%, 89.7%, 83.6%), and OD (92.2%, 87.2%, 82.4%) was comparable. The eGFR in YD was comparable to ID but better than OD (86.5 vs. 79.7 vs. 67.2 mL/min/1.73 m², p 0.139 and <0.0003). Primary graft non-function was more frequent in TX from YD than ID and OD (3.7% vs. 0.3 and 0.7%, p = 0.004); the incidence of vascular thrombosis was similar. The aforementioned data show that pediatric recipients of YD had equivalent patient and graft survival. Although primary graft non-function was higher, eGFR of functioning grafts was comparable to ID. With further improvements in care, kidneys from YD may present a viable option for transplantation.

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Limbers CA, Neighbors K, Martz K, Bucuvalas JC, Webb T, Varni JW, Alonso EM, on behalf of the Studies of Pediatric Liver Transplantation (SPLIT) Functional Outcomes Group (FOG). Health-related quality of life in pediatric liver transplant recipients compared with other chronic disease groups.
Pediatr Transplantation 2011: 15: 245–253. © 2010 John Wiley & Sons A/S.

Abstract:  This cross-sectional, multicenter cohort study compares the level of HRQOL of pediatric LT recipients to children with other chronic health conditions. LT sample included 873 children who survived at least 12 months following LT. Six chronic disease samples were compiled from numerous studies, including over 800 patients with JRA, type 1 diabetes, cancer in remission, cardiac disease, end-stage renal disease, and inflammatory bowel disease. Generic HRQOL was measured from both the parental and patient perspective using the PedsQL™ 4.0 Generic Core Scales. Pediatric LT patients reported better physical health than children with JRA. According to parents, pediatric LT recipients had better HRQOL than children on renal dialysis on all domains except school functioning. Across all domains but emotional functioning, pediatric LT recipients reported significantly lower HRQOL than children with type 1 diabetes. Overall, pediatric LT patients reported HRQOL comparable to that of children who had undergone renal transplantation and patients with cancer in remission. Pediatric LT patients manifested impaired HRQOL similar to that of children with chronic diseases and these data suggest that they face ongoing challenges that warrant monitoring and indicate a need for interventions to improve their HRQOL.

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Nguyen S, Martz K, Stablein D, Neu A. Wait list status of pediatric dialysis patients in North America.
Pediatr Transplantation 2011: 15: 376–383. © 2011 John Wiley & Sons A/S.

Abstract:  Kidney transplantation is the treatment of choice for the majority of pediatric patients with end-stage kidney disease. Previous studies demonstrating racial or gender disparities in access to the deceased donor transplant list could not evaluate the impact of medical concerns or patient preference on waitlist status. We undertook a retrospective cohort study using the NAPRTCS registry to begin to determine barriers to wait list registration for kidney transplantation among pediatric dialysis patients. Clinical and demographic factors were compared in listed vs. non-listed patients. Reasons cited for not listing patients were examined by clinical and demographic factors. At dialysis initiation, 88.7% of pediatric dialysis patients were not on the renal transplant wait list. Twelve months after dialysis initiation, 67.1% of pediatric dialysis patients were not on the wait list. The groups least likely to be on the wait list were infants (adjusted OR 0.23, 95% CI 0.16, 0.32) and girls (adjusted OR 0.78, 95% CI 0.67, 0.90) after adjusting for multiple confounders. The reason most often cited for not listing was medical reason for young infants and that the transplant workup was pending for girls. Further study is needed to identify barriers to wait list registration.

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Objective

The PedsQL™ (Pediatric Quality of Life Inventory™) is a modular instrument designed to measure health-related quality of life and disease-specific symptoms. The PedsQL™ Cognitive Functioning Scale was developed as a brief generic symptom-specific instrument to measure cognitive functioning. The objective of the present study was to determine the feasibility, reliability, and validity of the PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients.

Methods

The 6-item PedsQL™ Cognitive Functioning Scale and the PedsQL™ 4.0 Generic Core Scales were completed by pediatric liver transplant recipients ages 8–18 years (n = 215) and parents of pediatric liver transplant recipients ages 2–18 years (n = 502). Both patient self-report and parent proxy-report were available for 212 cases. The 72-item Behavior Rating Inventory of Executive Function (BRIEF), a widely validated measure of executive functioning, was completed by 100 parents and 56 teachers on a subset of patients.

Results

The PedsQL™ Cognitive Functioning Scale demonstrated minimal missing responses (0.0%, child report, 0.67%, parent report), achieved excellent reliability (α = 0.88 child report, 0.94 parent report), distinguished between pediatric patients with liver transplants and healthy children supporting discriminant validity, and was significantly correlated with the PedsQL™ 4.0 Generic Core Scales and the BRIEF supporting construct and concurrent validity, respectively. Pediatric liver transplants recipients experienced cognitive functioning comparable to long-term pediatric cancer survivors.

Conclusions

The results demonstrate the feasibility, reliability, discriminant, construct, and concurrent validity of the PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients.

▼ Purpose

We describe a cohort of children with chronic kidney disease due to vesicoureteral reflux. We compared the rate of progression to end stage renal disease in those patients to the rate in children with another cause of chronic kidney disease and identified potential risk factors for progression.

Materials and Methods

We performed a retrospective cohort study using data from the North American Pediatric Renal Trials and Collaborative Studies Registry. Patients with vesicoureteral reflux as a cause of chronic kidney disease were compared to 2 other diagnostic cohorts. The 3 groups were compared with respect to baseline characteristics and progression to end stage renal disease based on diagnostic category. Multivariate analysis was performed to identify risk factors for progression to end stage renal disease using Cox proportional hazards regression model.

Results

Data on 6,981 patients were available for analysis. Patients with vesicoureteral reflux as a cause of chronic kidney disease had a significantly slower rate of progression to end stage renal disease than patients with renal aplasia, hypoplasia or dysplasia and all other causes (log rank p <0.0001). On multivariate analysis of risk factors for progression to end stage renal disease in patients with vesicoureteral reflux as the cause of chronic kidney disease we found that, in addition to older age and more advanced chronic kidney disease stage, a history of urinary tract infection at registration was significantly associated with an increased risk of progression.

Conclusions

Children with vesicoureteral reflux had a slower rate of progression to end stage renal disease than children with another cause of chronic kidney disease even after controlling for multiple possible confounders. In children with vesicoureteral reflux as the cause of chronic kidney disease older age, higher chronic kidney disease stage and history of urinary tract infection are significantly associated with the risk of progression to end stage renal disease.

▼ Objective

To investigate the distribution of health-related quality of life in pediatric liver transplant recipients compared with a normative population.

Study design

This cross-sectional, multicenter study was conducted at select centers. Patients between 2 and 18 years of age, surviving liver transplantation by at least 12 months, were eligible. Parent/guardian fluency in English or Spanish was required. Children ≥8 years and parents of all children completed the age-appropriate versions of the PedsQL 4.0 (Mapi Research Institute, Lyon, France). Scores were compared with a sample of healthy children (n = 3911) matched by age group, sex, and race/ethnicity and with a sample of pediatric patients with cancer receiving chemotherapy and/or radiation.

Results

Participants included 65% (873/1339) of eligible patients. Mean age was 8.17 ± 4.43 years, and 55% were female. The total and subscale scores of PedsQL 4.0 were lower than in healthy children (P < .001), with effect sizes for self-report ranging from −0.25 for Emotional Functioning to −0.68 for School Functioning. Patients and their parents reported better physical functioning than patients with cancer but similar social and school functioning. Correlations between parent and self-reports were in the moderate agreement range.

Conclusions

Pediatric liver transplant recipients and their parents report lower health-related quality of life than control subjects with some domains equal to children receiving cancer therapy.

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Background. Studies show that adult dialysis patients with allograft failure have increased mortality and morbidity on dialysis compared to transplant naïve patients. We previously showed comparable mortality risk in pediatric dialysis patients after allograft failure compared to transplant naïve patients; the impact on morbidity is less clear. Specifically, the effect of allograft failure on school attendance in pediatric patients has not previously been studied.

Methods. Using the North American Pediatric Renal Trials and Collaborative Studies database, we compared school attendance between transplant naïve and allograft failure patients from 1 January 1992 to 31 December 2007. School attendance was compared between the two groups at 6 and 12 months after dialysis initiation using a chi-square test. Factors which can potentially impact on school attendance data were evaluated using a multivariate logistic regression analysis.

Results. There were 2783 patients who had a follow-up at least 6 months after dialysis initiation and were capable of attending school during the study period. Patients were categorized by transplant history: previous allograft failure (n = 576) and transplant naïve (n = 2207). At 6 months, full-time school attendance was 67.2% in the allograft failure group and 72.3% in the transplant naïve group (P = 0.0164). At 12 months, attendance was 68.6% in the allograft failure group and 72.5% in the transplant naïve group (P = 0.103). After covariate adjustment, transplant failure did not impact school attendance at either 6 or 12 months follow-up [hazard ratio (HR) 1.12, confidence interval (CI) 0.91–1.39; HR 0.99, CI 0.78–1.27, respectively].

Conclusions. Children with failed allografts who return to dialysis have comparable school attendance compared to their transplant naïve dialysis counterparts. These results suggest that transplant failure is not an adverse prognostic factor for quality of life as measured by full-time school attendance.

▼ Objective

To evaluate and characterize the degree of blood pressure (BP) control in children on chronic dialysis and to identify significant predictors of hypertension and BP control in these patients.

Study design

Linear and logistic regression models were used to examine trends in BP and BP control in a cross-sectional sample of patients on chronic dialysis aged 1-21 years enrolled in the North American Pediatric Renal Trials and Collaborative Studies registry from 1992-2008.

Results

At 6 months after dialysis initiation, 67.9% of patients had uncontrolled or untreated hypertension, and 57.8% were prescribed antihypertensive medications. More recent year of dialysis initiation was associated with a higher use of antihypertensive medication and lower systolic BP and diastolic BP z scores (P < .001) measured over time from 6 months to 3 years post dialysis initiation. Other factors associated with higher BP included black race, glomerular disease, younger age, hemodialysis (systolic BP only), and antihypertensive use. There were significant differences in BP control by dialysis modality and disease etiology, with patients on hemodialysis or those with glomerular diseases having the highest percentage of uncontrolled hypertension.

Conclusions

Despite widespread antihypertensive use, many pediatric patients on dialysis are at risk for untreated or uncontrolled hypertension. Additional efforts are needed to improve management of hypertension in these children.

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The NAPRTCS transplant registry has collected clinical information on children undergoing kidney transplantation since 1987 and now includes information on 11 603 kidney transplants in 10 632 patients. Since the first data analysis in 1989, NAPRTCS reports have documented marked improvements in outcome after kidney transplantation in addition to identifying factors associated with both favorable and poor outcomes. Patient demographics have changed over the course of the registry with a decrease in the percentage of white recipients from a high of 72% in 1987 to less than 43% in 2007. The percentage of living donors decreased to its lowest point in 2007 at 37%. Acute rejection rates continue to decline with improvements in short- and long-term graft survival. Recently, NAPRTCS data have been used as a source of benchmark data for pediatric kidney transplant centers.

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The NAPRTCS transplant registry has collected clinical information on children undergoing kidney transplantation since 1987 and now includes information on 11 603 kidney transplants in 10 632 patients. Since the first data analysis in 1989, NAPRTCS reports have documented marked improvements in outcome after kidney transplantation in addition to identifying factors associated with both favorable and poor outcomes. Patient demographics have changed over the course of the registry with a decrease in the percentage of white recipients from a high of 72% in 1987 to less than 43% in 2007. The percentage of living donors decreased to its lowest point in 2007 at 37%. Acute rejection rates continue to decline with improvements in short- and long-term graft survival. Recently, NAPRTCS data have been used as a source of benchmark data for pediatric kidney transplant centers.