Search

Many transplant physicians are faced with questions from their patients about the safety and long-term consequences of pregnancy following transplantation. To better understand how pregnancies are managed and to clarify the outcome of pregnancy after transplantation, a survey questionnaire was developed and mailed to all medical and surgical directors of transplant centers throughout the United States; responses were obtained from 59.1% of the transplant centers. Although many opinions were collected, most respondents conceded that their opinions were based on personal experience rather than evidence-based. The underutilization of existing information was revealing and highlighted a need for an evidence-based approach to care of the pregnant transplant recipient and her offspring. The survey results, reported in this article, led to formation of a consensus conference to determine the optimal approach to pregnant transplant recipients and to define what is currently known and unknown about reproduction and transplantation. (Progress in Transplantation. 2006;16:127-132) [ABSTRACT FROM AUTHOR]

Importance: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease (ESKD) across the lifespan. While 10% to 15% of children and 3% of adults who develop ESKD have FSGS, it remains uncertain whether the natural history differs in pediatric vs adult patients, and this uncertainty contributes to the exclusion of children and adolescents in clinical trials., Objective: To examine whether there are differences in the kidney health outcomes among children, adolescents, and adults with FSGS., Design, Setting, and Participants: This cohort study used pooled and parallel analyses, completed July 5, 2022, from 3 complimentary data sources: (1) Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE); (2) FSGS clinical trial (FSGS-CT); and (3) Kidney Research Network (KRN). NEPTUNE is a multicenter US/Canada cohort study; FSGS-CT is a multicenter US/Canada clinical trial; and KRN is a multicenter US electronic health record-based registry from academic and community nephrology practices. NEPTUNE included 166 patients with incident FSGS enrolled at first kidney biopsy; FSGS-CT included 132 patients with steroid-resistant FSGS randomized to cyclosporine vs dexamethasone with mycophenolate; and KRN included 184 patients with prevalent FSGS. Data were collected from November 2004 to October 2019 and analyzed from October 2020 to July 2022., Exposures: Age: children (age <13 years) vs adolescents (13-17 years) vs adults (≥18 years). Covariates of interest included sex, disease duration, APOL1 genotype, urine protein-to-creatinine ratio, estimated glomerular filtration rate (eGFR), edema, serum albumin, and immunosuppressive therapy., Main Outcomes and Measures: ESKD, composite outcome of ESKD or 40% decline in eGFR, and complete and/or partial remission of proteinuria., Results: The study included 127 (26%) children, 102 (21%) adolescents, and 253 (52%) adults, including 215 (45%) female participants and 138 (29%) who identified as Black, 98 (20%) who identified as Hispanic, and 275 (57%) who identified as White. Overall, the median time to ESKD was 11.9 years (IQR, 5.2-19.1 years). There was no difference in ESKD risk among children vs adults (hazard ratio [HR], 0.67; 95% CI, 0.43-1.03) or adolescents vs adults (HR, 0.85; 95% CI, 0.52-1.36). The median time to the composite end point was 5.7 years (IQR 1.6-15.2 years), with hazard ratio estimates for children vs adults of 1.12 (95% CI, 0.83-1.52) and adolescents vs adults of 1.06 (95% CI, 0.75-1.50)., Conclusions and Relevance: In this study, the association of FSGS with kidney survival and functional outcomes was comparable at all ages.

Rationale & Objective: Remission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to evaluate whether reductions in proteinuria after treatment are associated with greater kidney survival., Study Design: Cohort analysis of clinical trial participants., Setting & Participants: Patients with steroid-resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine with mycophenolate mofetil plus dexamethasone., Predictors: Reduction in proteinuria measured during 26 weeks after initiating treatment., Outcomes: Repeated assessments of estimated glomerular filtration rate (eGFR) and time to a composite outcome of kidney failure or death assessed between 26 weeks and 54 months after randomization., Analytical Approach: Multivariable linear mixed-effects models with participant-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable time-varying Cox proportional hazards models were used to estimate the association of changes in proteinuria with time to the composite outcome., Results: 138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1-unit reduction in log-transformed urinary protein-creatinine ratio was associated with a 3.90mL/min/1.73m 2 per year increase in eGFR (95% CI, 2.01-5.79). This difference remained significant after adjusting for complete remission. There was an analogous relationship between time-varying proteinuria and time to the composite outcome: the HR per 1-unit reduction in log-transformed urinary protein-creatinine ratio was 0.23 (95% CI, 0.12-0.44)., Limitations: Limited to individuals with steroid-resistant FSGS followed up for a maximum of 5 years., Conclusions: These findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials., (Copyright © 2020 National Kidney Foundation, Inc. All rights reserved.)

Retransplantation accounts for approximately 15 % of the annual transplants performed in the USA, and in the recent International Collaborative Transplant Study report on pediatric patients 15.2 % of the 9209 patients included in the report were retransplant recipients. Although the significant advances in clinical management and newer immunosuppressive agents have had a significant impact on improving short-term allograft function, it is apparent that long-term allograft function remains suboptimal. Therefore, it is likely that the majority of pediatric renal allograft recipients will require one or more retransplants during their lifetime. Unfortunately, a second or subsequent graft in pediatric recipients has inferior long-term graft survival rates compared to initial grafts, with decreasing rates with each subsequent graft. Multiple issues influence the outcome of retransplantation, with the most significant being the cause of the prior transplant failure. Non-adherence-associated graft loss poses unresolved ethical issues that may impact access to retransplantation. Graft nephrectomy prior to retransplantation may benefit selected patients, but the impact of an in situ failed graft on the development of panel-reactive antibodies remains to be definitively determined. It is important that these and other factors discussed in this review be taken into consideration during the counseling of families on the optimal approach for their child who requires a retransplant.

Immunotolerance, which is nonimmunologic reactivity to specific tissue, was demonstrated in animals in the 1950s. However, despite assiduous efforts, it has not been reproduced in human solid-organ transplant to date. Fortuitously, clinical operational tolerance, which is stable graft function for > 1 year with no immunosuppression, has been demonstrated, primarily in a few nonadherent recipients of kidney and liver transplant. Vigorous efforts to identify a biomarker to distinguish recipients with clinical operational tolerance from nontolerant recipients have so far not been successful. However, weaning of immunosuppression in stable pediatric and adult liver transplant recipients has been successful in 60% and 20% of recipients. In kidney transplant recipients, clinical operational tolerance has been induced by combined kidney and hematopoietic cell transplant to induce chimerism and subsequent weaning of immunosuppression. Recently, the ex vivo expansion of autologous regulatory T cells with subsequent infusion has facilitated weaning of immuno suppression in liver transplant recipients. Protocols have been initiated to expand the use of regulatory T cells to kidney transplant recipients. These new methodologies have the potential to induce clinical operational tolerance in all recipients of a solid-organ transplant in the future, thus avoiding the long-term consequences of continued dependence on immunosuppressive medications for stable graft function.

Background and Objectives: Poor linear growth is common in children with CKD and has been associated with higher mortality. However, recent data in adult dialysis patients have suggested a higher risk of death in persons of tall stature. In this study, we aimed to examine the risk of all-cause and cause-specific mortality in children at both extremes of height at the time of first RRT., Design, Setting, Participants, & Measurements: Using the US Renal Data System, we performed a retrospective analysis of 13,218 children aged 2-19 years, who received their first RRT (dialysis or transplant) during 1995-2011. We used adjusted Cox models to examine the association between short (<3rd percentile) and tall (>3rd percentile) stature and risk of death, compared with less extreme heights., Results: Over a median follow-up of 7.1 years, there were 1721 deaths. Risk of death was higher in children with short (hazard ratio, 1.49; 95% confidence interval, 1.33 to 1.66) and tall stature (hazard ratio, 1.32; 95% confidence interval, 1.03 to 1.69) in adjusted analysis. In secondary analyses, there was a statistically significant interaction between height and body mass index categories (P=0.04), such that the association of tall stature with higher mortality was limited to children with elevated body mass index (defined as ≥95th percentile for age and sex). Children with short stature had a higher risk of cardiac- and infection-related death, whereas children with tall stature had a higher risk of cancer-related death., Conclusions: Children with short and tall stature are at higher mortality risk, although this association was modified by body mass index at time of first RRT. Studies to further explore the reasons behind the higher risk of mortality in children with extremes of height at the time of first RRT are warranted., (Copyright © 2016 by the American Society of Nephrology.)

Hematopoietic stem cell transplantation (HSCT) is an accepted treatment modality for various malignant and non-malignant disorders of the lympho-hematopoietic system. Patient survival rate has increased significantly with the use of this procedure. However, with the increase in disease-free patient survival rates, complications including various organ toxicities are also common. Kidney, liver, lung, heart, and skin are among those solid organs that are commonly affected and frequently lead to organ dysfunction and eventually end-organ disease. Conservative measures may or may not be successful in managing the organ failure in these patients. Solid organ transplantation has been shown to be promising in those patients who fail conservative management. This review will summarize the causes of solid organ (kidney, liver, and lung) dysfunction and the available data on transplantation of these solid organs in post-HSCT recipients.

Alemtuzumab is a monoclonal antibody targeting CD52 receptors on B and T lymphocytes and is an effective induction agent in pediatric renal transplantation. We report a seven-yr experience using alemtuzumab induction and steroid-free protocol in the pediatric population as safe and effective. Twenty-one pediatric deceased donor renal transplants were performed at a single academic institution. All received induction with single-dose alemtuzumab and were maintained on a steroid-free protocol using TAC and MMF immunosuppression. There were 15 males and six females in the study whose ages ranged from one to 19 yr. The average follow-up was 32 months (range from 12 to 78.2 months and median 33.7 ± 23.7 months). All patients had immediate graft function. Graft survival was 95%, and patient survival was 100%. Mean 12 and 36 months eGFR were 63.33 ± 21.01 and 59.90 ± 15.27 mL/min/1.73m(2), respectively. Three patients developed acute T-cell-mediated rejection due to non-adherence while no recipients developed cytomegalovirus infection, PTLD, or polyoma BK viral nephropathy. Steroid avoidance with single-dose alemtuzumab induction provides adequate and safe immunosuppression in pediatric deceased donor renal transplant recipients receiving TAC and low-dose MMF maintenance therapy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One of the ultimate goals of successful transplantation in pediatric solid organ transplant recipients is the attainment of optimal final adult height. This manuscript will discuss the attainment of height following solid organ transplantation in pediatric recipients of kidney, liver, heart, lung, and small bowel transplantation. Age is a primary factor with younger recipients exhibiting the greatest immediate catch up growth. Graft function is a significant contributory factor with a reduction in glomerular filtration rate correlating with poor growth in kidney recipients and the need for re-transplantation with impaired growth in liver recipients. The known adverse impact of steroids on growth has led to modification of steroid dosage and even to steroid withdrawal and steroid avoidance. In kidney and liver recipients, this has been associated with the development on occasion of acute rejection episodes. In infant heart transplantation, avoidance of maintenance corticosteroid immunosuppression is associated with normal growth velocity in the majority of patients. With marked improvement in patient and graft survival rates in pediatric organ graft recipients, it is timely that the quality of life issues, such as normal adult height, receive paramount attention. In general, normal growth post-transplantation should be an achievable goal that results in normal adult height for many solid organ transplantation recipients., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One of the ultimate goals of successful solid organ transplantation in pediatric recipients is attaining an optimal final adult height. This manuscript will discuss growth following transplantation in pediatric recipients of kidney, liver, heart, lung or small bowel transplants. Remarkably similar factors impact growth in all of these recipients. Age is a primary factor, with younger recipients exhibiting the greatest immediate catch-up growth. Graft function is a significant contributing factor, with a reduced glomerular filtration rate correlating with poor growth in kidney recipients and the need for re-transplantation with impaired growth in liver recipients. The known adverse impact of steroids on growth has led to modification of the steroid dose and even steroid withdrawal and avoidance. In kidney and liver recipients, this strategy has been associated with the development of acute rejection. In infant heart transplantation, avoiding maintenance corticosteroid immunosuppression is associated with normal growth velocity in the majority of patients. With marked improvements in patient and graft survival rates in pediatric organ recipients, quality of life issues, such as normal adult height, should now receive paramount attention. In general, normal growth following solid organ transplantation should be an achievable goal that results in normal adult height.

This NIH-funded multicenter randomized study of focal segmental glomerulosclerosis (FSGS) treatment compared the efficacy of a 12-month course of cyclosporine to a combination of oral pulse dexamethasone and mycophenolate mofetil in children and adults with steroid-resistant primary FSGS. Of the 192 patients enrolled, 138 were randomized to cyclosporine (72) or to mycophenolate/dexamethasone (66). The primary analysis compared the levels of an ordinal variable measuring remission during the first year. The odds ratio (0.59) for achieving at least a partial remission with mycophenolate/dexamethasone compared to cyclosporine was not significant. Partial or complete remission was achieved in 22 mycophenolate/dexamethasone- and 33 cyclosporine-treated patients at 12 months. The main secondary outcome, preservation of remission for 26 weeks following cessation of treatment, was not significantly different between these two therapies. During the entire 78 weeks of study, 8 patients treated with cyclosporine and 7 with mycophenolate/dexamethasone died or developed kidney failure. Thus, our study did not find a difference in rates of proteinuria remission following 12 months of cyclosporine compared to mycophenolate/dexamethasone in patients with steroid-resistant FSGS. However, the small sample size might have prevented detection of a moderate treatment effect.

Optimal therapy of patients with steroid-resistant primary focal segmental glomerulosclerosis (FSGS) remains controversial. This report describes the initial study design, baseline characteristics, and quality of life of patients enrolled in the FSGS Clinical Trial, a large multicenter randomized study of this glomerulopathy comparing a 12-month regimen of cyclosporine to the combination of mycophenolate mofetil and oral dexamethasone. Patients with age ranging 2-40 years, with an estimated glomerular filtration rate > 40 ml/min per 1.73 m², a first morning urine protein-to-creatinine ratio over one, and resistant to corticosteroids were eligible. The primary outcome was complete or partial remission of proteinuria over 52 weeks after randomization. In all, 192 patients were screened, of whom 138 were randomized for treatment. Ethnic distributions were 53 black, 78 white, and 7 other. By self- or parent-proxy reporting, 26 of the 138 patients were identified as Hispanic. The baseline glomerular filtration rate was 112.4 (76.5, 180.0) ml/min per 1.73 m², and urine protein was 4.0 (2.1, 5.3) g/g. Overall, the quality of life of the patients with FSGS was lower than healthy controls and similar to that of patients with end-stage renal disease. Thus, the impact of FSGS on quality of life is significant and this measurement should be included in all trials.

As most prior reviews on NA focus on adult transplant patients, there is a need for a comprehensive overview on adherence to the immunosuppressive regimen in pediatric kidney transplant patients. This systematic review searched for English-language papers (1990-2008) addressing the prevalence of NA to the immunosuppressive regimen, its consequences, determinants, and interventions in pediatric kidney transplant patients (< age 21 yr). We found 36 papers, showing a prevalence of NA (weighted mean) of 31.8% with adolescents being more at risk compared to younger patients. About 44% of all graft losses and 23% of late acute rejection episodes are associated with NA. Most studies investigated socio-economic, condition-related or treatment-related determinants. Only one educational intervention has been tested but yielded inconclusive results. NA to the immunosuppressive regimen is prevalent with serious clinical consequences in pediatric kidney transplant patients, but the economic consequences have not yet been explored. More studies on determinants of NA are needed. The literature currently lacks fully powered RCTs testing adherence-enhancing interventions. The results of this systematic review identify the gaps in the present evidence-based information regarding NA and can be used as a tool to pursue future adherence research in pediatric populations.

Dramatic changes have occurred in our understanding of the etiology of the growth retardation associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD) during the past 50 years. Significant interest has been focused on preventing and/or correcting the growth retardation because of the emergence of the dual therapeutic modalities of dialysis and renal transplantation to prolong the lives of infants, children, and adolescents afflicted with CKD and ESRD. These efforts have resulted in a significant improvement in the height Z-score over the past two decades of children with CKD and ESRD. This has had a salutary impact on the final adult height of such children which should hopefully lead to an enhanced quality of life in the future. This report addresses the progress that has been made in the management of growth retardation in the pediatric population with CKD and ESRD.

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.

This report is a summary of a 'Consensus Conference' on nonadherence (NA) to immunosuppressants. Its aims were: (1) to discuss the state-of-the-art on the definition, prevalence and measurement of NA, its risk factors and impact on clinical and economical outcomes and interventions and (2) to provide recommendations for future studies. A two-day meeting was held in Florida in January 2008, inviting 66 medical and allied health adherence transplant and nontransplant experts. A scientific committee prepared the meeting. Consensus was reached using plenary and interactive presentations and discussions in small break-out groups. Plenary presenters prepared a summary beforehand. Break-out group leaders initiated discussion between the group members prior to the meeting using conference calls and e-mail and provided a summary afterward. Conclusions were that NA: (a) is more prevalent than we assume; (b) is hard to measure accurately; (c) tends to confer worse outcomes; (d) happens for a number of reasons, and system-related factors including the patient's culture, the healthcare provider and the setting and (e) it is not currently known how to improve adherence. This consensus report provided some roadmaps for future studies on this complicated, multifaceted problem.

rhGH, widely used to optimize linear growth in children with ESRD, also modulates B-cell precursor development and may be associated with malignancy development. To determine if rhGH use in children was associated with higher risk of PTLD, we analyzed retrospectively collected data on children with CRI, on dialysis or with renal transplants in a large multi-center registry of children with ESRD. Of the 194 LPD patients currently listed in the registry, 41 were previously enrolled in the CRI registry and 18/41 (43.9%) used rhGH during their period with CRI. Among CRI patients who later received a transplant, rates of PTLD post-transplant were significantly higher among rhGH users (18/407 or 4.4%) compared to patients who never used rhGH during their CRI follow-up and received a transplant (23/1240 or 1.9%, p = 0.009). After adjusting for the confounders of recipient age (at CRI and at transplant) and transplant era, the use of rhGH pretransplant was associated with a borderline higher risk for PTLD (odds ratio 1.88, 95% CI = 1.00-3.55, p = 0.05). In contrast, use of rhGH during dialysis or post-transplant only was not associated with a higher risk for PTLD. Continued monitoring is recommended.

Renal transplantation is the goal for the pediatric patient with end stage renal disease. Recent advances in technology and immunosuppression have greatly enhanced patient and graft survival. However, the chronic immunosuppression exposes children to multiple complications and side effects. The current objective of pediatric renal transplantation is to develop management strategies which minimize or eliminate immunosuppression morbidities in order to maximize the growth and development of this unique population.

This review describes the state-of-the-art on quality of life (QOL) in kidney transplant (KTx) recipients. More specifically, posttransplant QOL is compared with the pretransplant evaluation, with other chronically ill patient populations, and with healthy subjects. Determinants, consequences, and potential interventions to improve QOL are also summarized. However, because of the methodological diversity of published articles, this review starts with addressing some conceptual and methodological concerns surrounding research on QOL in general and in KTx recipients specifically. The ultimate goal of this review was to identify the gaps in the state-of-the-art evidence and to provide some guidelines for conduct of research in the future.

Growth retardation frequently accompanies chronic kidney disease in children. Unfortunately, this retardation persists in magnitude despite assiduous therapeutic efforts, adequate dialytic intervention, and successful transplantation. The age of the patient at transplantation, allograft function, and corticosteroid dosage are the major factors that contribute to persistent suboptimal growth following renal transplantation. Recent data indicate that the use of recombinant human growth hormone might efficaciously improve growth velocity in the persistently growth-retarded allograft recipient. Attainment of optimum final adult height is predicated on optimum height at the time of transplantation, persistent optimum allograft function, minimization or avoidance of corticosteroid treatment, and, possibly, use of recombinant human growth hormone, especially to potentially maximize the pubertal growth spurt.

The incidence of recurrence of nephrotic syndrome/focal segmental glomerulosclerosis (NS/FSGS) is variable (~30%). The incidence of recurrence is less in African-Americans than in whites and Hispanics. Graft survival rates are decreased in recipients with FSGS, especially if remission of the NS is not achieved in those with recurrence. Although controversial, the use of living donor (LD) transplants are not contraindicated; however, obligatory heterozygote parental grafts with a podocin mutation should be used with caution. Optimal treatment to induce a remission post-transplant has not been delineated. Pre-transplant and/or prophylactic post-transplant pre-operative plasmapheresis (PP) for high-risk patients--especially those with recurrence in a previous graft--may be promising. An international multicenter controlled study is required to delineate the optimal approach to prevent and/or treat the recurrence of NS/FSGS.

This article reviews trends in pediatric solid organ transplantation over the last decade, as reflected in OPTN/SRTR data. In 2004, children younger than 18 years made up nearly 3% of the 86,378 candidates for organ transplantation and nearly 7% of the 27,031 organ transplant recipients. Children accounted for nearly 14% of the 7152 deceased organ donors. The transplant community recognizes important differences between pediatric and adult organ transplant recipients, including different etiologies of organ failure, surgical procedures that are more complex or technically challenging, effects of development on the pharmacokinetic properties of common immunosuppressants, unique immunological aspects of transplant in the developing immune system and increased susceptibility to posttransplant complications, particularly infectious diseases. For these reasons, and because of the impact of end-stage organ failure on growth and development, the transplant community has generally provided pediatric candidates with special consideration in the allocation of deceased donor organs. Outcomes following kidney, liver and heart transplantation in children often rank among the best. This article emphasizes that the prospects for solid organ transplantation in children, especially those aged 1-10 years are excellent. It also identifies themes warranting further consideration, including organ availability, adolescent survival and challenges facing pediatric transplant clinical research.

The literature regarding the etiology and incidence of short and long-term renal functional impairment in pediatric liver allograft recipients was reviewed. Most of the reports include recipients receiving cyclosporine as the primary immunosuppressant. Using calculated glomerular filtration rate (cGFR), creatinine clearance or the serum creatinine level will lead to an overestimation of GFR. In contrast to data in adults, there are a limited number of pediatric recipients whose renal dysfunction has progressed to chronic kidney disease or end-state renal disease. Calcineurin inhibitors minimization has proven effective in reversing or preventing progressive deterioration of GFR; however, rejection episodes and complications have limited efficacy of this approach. Future multicenter studies using optimal GFR measurements are required to delineate the magnitude of renal dysfunction in pediatric recipients.

It has been almost 50 years since the first child was born to a female transplant recipient. Since that time pregnancy has become common after transplantation, but physicians have been left to rely on case reports, small series and data from voluntary registries to guide the care of their patients. Many uncertainties exist including the risks that pregnancy presents to the graft, the patient herself, and the long-term risks to the fetus. It is also unclear how to best modify immunosuppressive agents or treat rejection during pregnancy, especially in light of newer agents available where pregnancy safety has not been established. To begin to address uncertainties and define clinical practice guidelines for the transplant physician and obstetrical caregivers, a consensus conference was held in Bethesda, Md. The conferees summarized both what is known and important gaps in our knowledge. They also identified key areas of agreement, and posed a number of critical questions, the resolution of which is necessary in order to establish evidence-based guidelines. The manuscript summarizes the deliberations and conclusions of the conference as well as specific recommendations based on current knowledge in the field.

Data from the NAPRTCS database were analyzed for growth, allograft function, and targeted adverse events (AE) over a 5-year period in 513 recipients who received recombinant human growth hormone (rhGH) treatment and compared with the outcome of 2,263 concurrent controls who did not receive rhGH. Recipients less than 10 years of age grew better than older recipients. Final adult height was superior in the rhGH-treated group compared with the control group. Allograft function and graft failure rate was similar in the rhGH-treated and control groups. No increased incidence of AE was noted in the rhGH-treated group. rhGH is effective and safe for use in growth-retarded pediatric renal allograft recipients.

The following is a summary report of an extensive review of the literature from 1966 to 2001 on growth and development in children receiving kidney, liver and heart transplants. The literature was assessed for relevancy to current clinical practice and for reliability and generalizability of the inferences based on the study design, controls, sample size, age distribution, confounding factors, use of standardized instruments, and consistency with other findings. While studies on growth are included in the review, the main emphasis is on research in cognitive and psychosocial development since these areas have been far less thoroughly studied and contain various methodological deficiencies. On the basis of the literature review both general methodological recommendations and specific recommendations for future research studies are made. Access to the full is provided on the World Wide Web at http://light.emmes.com/pedstransplantation/., (Copyright 2004 Blackwell Munksgaard)

End-stage renal disease (ESRD) is a major cause of morbidity in children. Besides its high cost to society, ESRD carries significant mortality. Chronic renal insufficiency (CRI) often precedes ESRD. Identifying factors that correlate with the rate of progression to ESRD is beneficial in the management of children with CRI. Since 1994 the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) has extended its registry to include children with CRI, defined as creatinine clearance ( C(Cr)) <75 ml/min per 1.73 m(2). As of January 2001, our database registered 4,666 children (<20 years of age) with CRI. Data analysis showed that at least 40% of patients entered had congenital urological anomalies; 39% of patients were followed for at least 3 years. Follow-up data showed that 31% of all registered patients progressed to ESRD by the end of the reporting period. There was a correlation between CRI and several co-morbid clinical factors: low hematocrit, hypoalbuminemia, hypocalcemia, hyperphosphatemia, and hyperparathyroidism, and the rate of progression to ESRD. Primary clinical diagnosis and the age at entry into registry were additional factors that correlated with the rate of progression to ESRD. The main cause of hospitalization in this registry was infection, which accounted for 45% of hospital admissions. Growth delay measured by standard deviation score at baseline was -1.40 at the time of registration. Our data suggest potential areas of improved care that could impact the onset of ESRD.

Using the North American Renal Transplant Cooperative Study (NAPRTCS) database, we performed a retrospective cohort study of 986 pediatric renal transplant recipients (index transplant 1997-2000) who were treated either with Cyclosporine A (CSA), Mycophenolate Mofetil (MMF) and steroids (n = 766) or tacrolimus (TAC), MMF and steroids (n = 220) to examine potential difference in clinical outcomes between these two groups. In the first year post-transplant, time to first rejection (29.1% vs. 29%, p = 0.840), risk for rejection [Adjusted Relative Risk (aRR) 1.01, 95% Confidence Interval (CI) 0.77, 1.323], graft survival (96.8% vs. 97.9%, p = 0.607) and risk for graft failure (aRR 0.988, 95% CI 0.64, 1.928) were not significantly different in TAC and CSA-treated patients. At 2 yr post-transplant, there was also no difference in risk for rejection (aRR 0.918, 95% CI 0.669, 1.259), graft survival (91.4% vs. 95.1%, p = 0.152) and risk for graft failure (aRR 0.702, 95% CI 0.461, 1.762) in the subset of 391 CSA-treated patients and 77 TAC-treated patients on whom 2 yr follow data were available in the database. TAC-treated patients were significantly less likely to require antihypertensive medication at 1 yr [aRR 0.74 (95% CI 0.454, 0.637)] and 2 yr post-transplant [aRR 0.67 (95% CI 0.56, 0.793)]. At 1 yr post-transplant, TAC-treated patients enjoyed a higher mean GFR as estimated by the Schwartz formula [89.1 mL/min/1.73 m(2) (SE 2.64) vs. 78.6 mL/min/1.73 m(2) (SE 1.07), p = 0.0003]. In addition, in the subset of patients with 2 yr of follow-up, TAC patients had a higher mean GFR at both 1 yr [98.6 mL/min/1.73 m(2) (SE 3.83) vs. 78.0 mL/min/1.73 m(2) (SE 1.44), p = 0.0003] and 2 yr post-transplant [96.7 mL/min/1.73 m(2) (SE 3.33) vs. 73.2 mL/min/1.73 m(2) (SE 1.48), p < 0.0001]. In summary, TAC and CSA, in combination with MMF and steroids, produce similar rejection rates and graft survival in pediatric renal transplant recipients. However, TAC is associated with improved graft function at 1 and 2 yr post-transplant. Further analysis as more patient data are obtained will be necessary to determine if this difference in graft function persists and translates into improved graft survival.

Objective: Recombinant human growth hormone (rhGH) has been used to improve the growth retardation associated with chronic renal insufficiency (CRI) and end-stage renal disease. We determined the incidence of one of four targeted adverse events (AEs): malignancy, slipped capital femoral epiphysis (SCFE), avascular necrosis (AN), and intracranial hypertension (ICH)., Study Design: During a 6.5-year period, we prospectively assessed patients enrolled in the CRI, dialysis, and transplant registries of the North American Renal Transplant Cooperative Study. The availability of an untreated control population facilitated determining whether or not there was the association between the AE and rhGH treatment., Results: Of the targeted AE, the only significant relation with rhGH treatment was the presence of ICH in patients with CRI; however, in all 3 instances, ICH occurred 2, 50, and 1131 days after discontinuation of rhGH. Considering that the mechanism of ICH in rhGH-treated patients is thought to be increased CSF production, rhGH probably had no role in the development of ICH in at least 2 of the 3 patients with CRI. A number of nontargeted AE were identified that have been associated with rhGH treatment in patients without renal disease. The incidence of glucose intolerance, pancreatitis, progressive deterioration of renal function, acute allograft rejection, and fluid retention were not more frequent in those receiving rhGH treatment compared with the control population., Conclusions: This report validates the importance of a control population in ascribing AE to any therapeutic intervention. Previously identified AE associated with rhGH treatment are infrequent in patients with CRI and end-stage renal disease.

In an attempt to delineate the role of automated peritoneal dialysis (APD) in the management of the pediatric patient with end-stage renal disease (ESRD), the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) dialysis registry database was queried concerning the incidence and outcome of APD compared to those enrolled who were undergoing continuous ambulatory peritoneal dialysis (CAPD). During the 10-year period from January 1, 1992 to January 1, 2002, 65% of the 4150 index dialysis patients enrolled in NAPRTCS underwent peritoneal dialysis (PD). APD was the dialysis modality of 69% of those choosing PD, indicating that APD was the primary dialysis modality for children during this time interval. This initial comparison of APD and CAPD from the NAPRTCS dialysis registry database indicated that there was a higher percentage of younger patients choosing APD, the time to transplantation was shorter for the CAPD patient, and the incidence and time to first peritonitis episode was significantly (p = 0.006) better in the APD population. There was no difference in the other parameters evaluated between the APD and CAPD patients. These data indicate the significant role of APD in the management of pediatric patients with ESRD, especially in infants, who frequently require an extended period of dialysis prior to reaching the eligibility criteria for transplantation.

Background: Growth retardation persists in renal allograft recipients despite successful transplantation. The etiology is multi-factorial including the adverse effects of corticosteroids, suboptimal allograft function, and perturbations of the GH/GF axis. Recombinant human growth hormone (rhGH) has been effective in improving growth velocity; however, allograft dysfunction has been reported. Therefore, a randomized controlled study was undertaken., Methods: Sixty-eight growth retarded pediatric renal allograft recipients were enrolled in a one-year randomized controlled study to determine the efficacy and safety of rhGH. A protocol biopsy was performed prior to enrollment., Results: After one year, the delta SDS (standardized height) was +0.49 +/- 0.10 in the treatment group (N = 30) compared to -0.10 +/- 0.08 in the control group (N = 22; P < 0.001). During the first year, there were no rejection episodes in the treatment group and three in the control group. After the first year, when all recipients were receiving rhGH, there were three patients in the treatment group and two patients in the control group who experienced an acute rejection episode. Prior to enrollment, more than one acute rejection episode was predictive of a subsequent rejection following enrollment. There was no difference in adverse events between the two groups., Conclusion: In conclusion, rhGH is effective in improving the growth velocity of pediatric renal allograft recipients and is not associated with an increase in adverse events.