Living donor lobar lung transplantation: the pediatric experience

Living donor (LD) lobar lung transplantation is now an accepted alternative to cadaveric lung transplantation in selected patients with end-stage lung disease. This study reviews the Childrens Hospital Los Angeles LD experience of 17 patients (mean 13.2 +/- 2.7 yrs; range 9.3-18.5 yrs). 12 LD patients had end-stage cystic fibrosis, 4 had primary pulmonary hypertension, and 1 child had bronchiolitis obliterans. LD candidates must meet the same criteria as for cadaveric lung transplant candidates. Donor candidates are rigorously screened (physically and psychologically) prior to acceptance for lobectomy. LD patients receive the same triple immunosuppression regimen as our cadaveric recipients (prednisone, cyclosporine/FK506, and azathioprine/mycophenolate). Comparison of rejection episodes, incidence of bronchiolitis obliterans, pulmonary function tests, exercise stress tests, and cardiac catheterization data was made between LD and cadaveric lung transplantation (CL) pediatric recipients. Donor outcomes were also reviewed. In our pediatric program, the 1-year survival rate for LD recipients is currently 81%, which compares favorably with the ISHLT average of 70% for pediatric transplant patients. The incidence of rejection is about the same for LD and CL recipients, but the episodes are less severe for pediatric LD patients. There have been no histological cases of bronchiolitis obliterans syndrome in our LD recipients. Although there have been questions as to whether transplanted lobes can supply comparable pulmonary reserve to whole cadaveric lungs, the lung volumes (TLC and VC), expiratory flow rates, maximal exercise stress tests, and pulmonary artery pressures (no evidence of pulmonary hypertension) in LD patients are not significantly different to CL recipients in our institution. Besides pain from the thoracotomy, the donors have a decrease of 16% (right lower lobe donor) and 18% (left lower lobe donor) in their vital capacity. Otherwise, there have been no major complications to the donors and most have resumed their usual activities. Based on outcomes, pulmonary function tests, exercise stress tests, and hemodynamic studies as well as low donor morbidity, living donor double lobar lung transplantation is a viable alternative to cadaveric lung transplantation in selected pediatric patients with end-stage lung disease.     

BK virus-associated hemorrhagic cystitis in a pediatric lung transplant recipient

Abstract:  BKV was first postulated to be a potential pathogen in 1971 when it was isolated in the urine of a renal transplant recipient. The pathology of BKV is generally confined to the urinary tract. In renal transplant recipients, BKV has been associated with hemorrhagic cystitis, urethral stenosis, and interstitial nephritis. Reports of BKV infection in lung transplant recipients are limited to a few case reports in adult patients. A recent report revealed that up to 32% of adult lung transplant recipients may shed BKV in their urine without symptoms or renal dysfunction. To our knowledge, there are no published reports of pediatric lung transplant recipients with BKV-associated hematuria. We hereby report a case of BKV-induced hemorrhagic cystitis in a pediatric lung transplant recipient.     

Prevalence of renal dysfunction in tacrolimus‐treated pediatric transplant recipients: A systematic review

Renal dysfunction after non‐renal transplantation in adult tacrolimus‐treated transplant patients is well documented. Little is known about its prevalence in children. Age‐related changes in both disposition and effect of tacrolimus as well as renal function may preclude extrapolation of adult data to children. To systematically review the literature on renal dysfunction in non‐renal pediatric transplant recipients treated with tacrolimus. PubMed/Medline, Embase, and Google were searched from their inception until April 19, 2012, with the search terms “tacrolimus,” “renal function,” “transplantation,” and “children.” Eighteen of 385 retrieved papers were considered relevant. Twelve dealt with liver, four with heart transplant, one with heart and lung transplant, and one with intestinal recipients. Reported prevalences of mild and severe chronic kidney disease ranged from 0% to 39% and 0% to 71.4%, respectively, for liver, and from 22.7% to 40% and 6.8% to 46%, respectively, for heart and/or lung transplant recipients. Ranges remained wide after adjusting for follow‐up time and disease severity. Possible explanations are inclusion bias and definitions used for renal dysfunction. A considerable proportion of pediatric non‐renal transplant patients who receive tacrolimus‐based immunosuppression, appear to suffer from chronic kidney disease. This conclusion warrants further research into the real risk, its risk factors, and individualization of immunosuppressant therapy.     

Four pediatric patients with autosomal recessive polycystic kidney disease developed new‐onset diabetes after renal transplantation

NODAT is increasingly prevalent. Compared with adult recipients, NODAT is less prevalent in pediatric renal transplant recipients; however, some risk factors for its development in young patients have been defined. We report four pediatric renal transplant recipients with ARPKD who developed NODAT. We review the current pediatric NODAT literature and hypothesize that ARPKD may be an additional risk factor for NODAT.     

Outcomes of kidney transplantation in children with nephronophthisis: An analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry

Abstract: NPHP is an autosomal recessive chronic tubulointerstitial nephropathy that progresses to ESRD. In the 2006 NAPRTCS report, NPHP was the primary diagnosis in 2.8% of all renal transplant patients. At our pediatric center, that covers a population in which the NPHP1 gene is prevalent, 24% of transplant recipients had a primary diagnosis of NPHP. Since no previous literature reports have documented kidney transplant outcomes in patients with NPHP, a review of the 2006 NAPRTCS database was performed. The results of this review illustrate that patients with NPHP as their underlying kidney disease have a significantly better overall graft survival when compared with all other patients registered in the NAPRTCS database. Sub‐analysis demonstrated that this benefit is statistically significant only for LD kidney transplant recipients. CrCl was better in NPHP at all time points from transplant up to five‐yr follow‐up. Moreover, in NPHP LD transplant recipients the decline of CrCl over five yr was slower compared with non‐NPHP LD transplant recipients. Rates of thrombosis, acute, and chronic rejection as well as causes of graft failure were similar in NPHP patients and all other patients. This review demonstrates that NPHP transplant recipients have excellent outcomes that are shown to be better compared with the general pediatric transplant population.     

Transition to adult care for pediatric liver transplant recipients: the Western Australian experience

Transition to adult care is a vulnerable period for pediatric transplant recipients and is associated with reduced medication compliance, graft loss, and increased mortality. Psychosocial outcomes in young adults differ between pediatric transplant recipients and their healthy peers. We conducted a single‐center, retrospective cohort study of all pediatric liver transplant recipients who were transitioned through our center. This study aimed to assess the outcomes of transitioned pediatric liver transplant recipients at an Australian center, including mortality, adherence, and psychosocial morbidity. The 1‐ and 5‐year survival rates following transition were 100% and 92%, respectively. There were no episodes of late rejection. In total, 66.7% of patients were compliant with immunosuppression and 61.1% of patients were compliant with clinic attendance. There was a significant relationship between medication compliance and clinic attendance, as well as presence of psychological issues with clinic non‐attendance. Psychosocial outcomes were in keeping with age‐matched data from the general population. All patients were employed or studying following transition. This is the first study of its kind in the Australian population, and outcomes were superior to published international data. Despite the demonstrated good outcomes, transition programs may improve healthcare engagement in this cohort.     

New insights into family functioning and quality of life after pediatric liver transplantation

Denny B, Beyerle K, Kienhuis M, Cora A, Gavidia‐Payne S, Hardikar W. New insights into family functioning and quality of life after pediatric liver transplantation. Abstract: Thorough research of the medical aspects of pediatric liver transplantation has given way to recent interest in the impact of the transplantation process on the QOL of recipients and their families. In this cross‐sectional study, we compared the family functioning and QOL of children (n = 30) aged between three and 16 yr (M = 10.10, s.d. = 3.62) who had received a liver transplant in the previous 1–12 yr (M = 5.31, s.d. = 3.44) with non‐transplant children (n = 33), as reported via parent proxy. Results showed that parents of pediatric liver transplant recipients made significantly more adjustments to family routines to accommodate their children, particularly in relation to childcare. Impaired family functioning was also found to be associated with decreased QOL. These preliminary findings of relative deficits in family functioning may inform psychosocial interventions to assist pediatric liver transplant patients and their families. Further investigation beyond a single‐center study incorporating subjective information from pediatric patients and their parents is recommended.     

Size‐reduced lung transplantation in children – an option worth to consider!

Benden C, Inci I, Weder W, Boehler A. Size‐reduced lung transplantation in children – an option worth to consider!
Pediatr Transplantation 2010: 14:529–533. © 2009 John Wiley & Sons A/S. Abstract: Lung transplantation is an accepted therapy for pediatric end‐stage lung disease. However, there is a shortage of suitable donor organs. Therefore, the use of downsized lung allografts seems a valuable option. We report our experience of downsized pediatric lung transplantation in comparison with standard full‐size pediatric lung transplantation over one decade. Pediatric recipients undergoing downsized or standard lung transplantation were included (January 1997–December 2006). We compared pretransplant clinical data and surgical and post‐operative complications and post‐transplant outcome. Ten pediatric lung transplants were performed (median patient age 15.6 yr [12.3–17.8]). Nine of 10 patients had CF. Five patients underwent standard full‐size lung transplantation; five had downsized lung transplants. “Downsized” recipients had significantly lower median height and weight Z‐scores. Donor/recipient length difference was significantly greater in the “Downsized” Group (p < 0.05). All patients had comparable post‐transplant functional outcome without additional surgical complications or morbidities in “downsized” recipients. Median post‐transplant survival was 65 months (5–77) in the “Standard” Group compared to 86 months (64–121) in the “Downsized” Group (p = 0.1). Our data suggest that downsized lung transplantation in pediatric recipients may have post‐transplant outcomes comparable to full‐size lung transplantation without significant complications.     

Outcomes of Pneumocystis jiroveci pneumonia infections in pediatric heart transplant recipients

PJP is known to cause significant morbidity and rarely death in immunosuppressed patients. The prevalence and outcomes of PJP in pediatric solid-organ transplant patients are not well established. This study utilizes data from the PHTS to establish the prevalence and outcome of PJP in pediatric heart transplant recipients. We conducted a retrospective cohort study using data from the PHTS, including data from 24 institutions between January 1, 1993, and December 31, 2004. Infections that occur in PHTS subjects are recorded in a standardized data collection form. The prevalence and outcomes of PJP in pediatric heart transplant recipients were determined. There were a total of 18 patients (1%) with PJP out of the 1854 pediatric heart transplant recipients in the PHTS database. A majority of PJP occurred two months to two yr post-transplant, and patients with PJP had a significantly decreased mortality compared with other fungal infections. PJP is an infrequent complication experienced by pediatric heart transplant recipients. Patients that have experienced PJP have an increased survival compared to patients with other fungal infections, and most PJP occurred within two yr of transplant.     

Subclinical cardiovascular changes in pediatric solid organ transplant recipients: A systematic review and meta‐analysis

CV disease is a major cause of morbidity and mortality following solid organ transplantation in adults. While the prevalence of multiple cardiometabolic risk factors is increased in pediatric solid organ transplant recipients, it is not clear whether they have subclinical CV changes. cIMT, central pWV, and CAC are indicative of subclinical CV disease, and, in adults, predict future CV events. The objective of this systematic review and meta‐analysis was to investigate the prevalence of subclinical CV changes, as measured by cIMT, pWV, and CAC among pediatric solid organ transplant recipients. We searched MEDLINE^® and EMBASE and conducted meta‐analysis for studies that evaluated cIMT, central pWV, and CAC among pediatric solid organ transplant recipients (kidney, lung, intestine and liver). The search identified nine eligible studies that included a total of 259 patients and 685 healthy controls. Eight studies reported on kidney transplant recipients and one study on a combined cohort of kidney and liver transplant recipients. The mean cIMT of transplant recipients was significantly higher than that of healthy controls (mean difference = 0.05 mm, 95% CI 0.02–0.07; p < 0.0001) with an estimated pooled prevalence of elevated cIMT of 56.0% (95% CI 17.0–95.0). The one study that assessed pWV showed increased vascular stiffness in transplant recipients compared to healthy controls. No studies assessing for CAC were found. There were limited data regarding subclinical CV disease following pediatric solid organ transplantation. In conclusion, kidney transplantation in childhood is associated with a higher prevalence of subclinical CV changes compared to healthy children. Longitudinal studies are needed to determine whether children have increased CV morbidity and mortality after transplantation.     

The psychosocial challenges of solid organ transplant recipients during childhood

Annunziato RA, Jerson B, Seidel J, Glenwick DS. The psychosocial challenges of solid organ transplant recipients during childhood. Abstract: A large proportion of pediatric solid organ transplant recipients are young children, yet dedicated studies on the challenges faced by these patients are sparse. The present article aims to provide a summary of key considerations for pediatric solid organ transplant teams, describing what challenges are more likely for younger patients and how they might identify and address these circumstances. Our findings suggest that the mental health of patients and caregivers, issues at school, neurocognitive difficulties, and self-management are areas of particular relevance for children. We offer several recommendations that stem from these identified areas of concern. Dedicated focus on the well-being of younger patients could in the long-term stave off adverse events that are often associated with adolescence. In the short-term, certainly intervening in any of these domains could lead to improved quality of life during childhood.     

Varicella vaccination in pediatric kidney and liver transplantation

Prelog M, Zimmerhackl LB. Varicella vaccination in pediatric kidney and liver transplantation.
Pediatr Transplantation 2010: 14: 41–47. © 2009 John Wiley & Sons A/S.
Abstract:  Reports about efficacy and safety of live-virus attenuated vaccines in patients before and after transplantation are mainly based on small patient numbers, making general recommendations for this patient population difficult. Children and adults as well as their close relatives and contact persons should be preferably immune to VZV before solid organ transplantation to avoid VZV-associated complications, thus making VZV vaccination necessary in susceptible individuals. The following literature review focused on efficacy and safety of VZV vaccination in pediatric kidney and liver transplant recipients. Review of literature also revealed that in all pediatric transplant candidates, humoral and cellular immunity against VZV should be consistently monitored to assess waning immunity under immunosuppressive treatment. This approach is desirable to estimate the risk of severe varicella disease after exposure in these patients.     

Parenthood in pediatric liver transplant patients

Liver transplantation has become a universally accepted treatment for numerous congenital and acquired hepatic disorders that cause liver failure. Without liver transplantation, patients in their reproductive years are afflicted with oligospermia or azoospermia in men and amenorrhea in women, with infertility being a consequence in both sexes. The aim of this study is to describe our experiences concerning the parenthood of pediatric individuals who are successful recipients of liver transplantations coming into the reproductive years of life. We retrospectively analyzed data of 207 pediatric liver transplanted patients (96 women, 111 men). Among them, three women conceived and delivered four babies, and two men admitted to paternity of two children after they all had been recipients of liver transplants. All female transplant recipients had received tacrolimus-based immunosuppression. Preterm delivery was the most clinically important complication among these patients. Only one of the female patients experienced hypercalcemia during the pregnancy. None had any other complications such as hypertension, preeclampsia, cholestasis, or diabetes. There was no graft insufficiency, rejection, or birth defect. We concluded that maternity and paternity in liver transplant patients show normal outcomes even though this procedure occurs in childhood, and pregnancy did not seem to impair graft function in patients receiving immunosuppressive drugs.     

Gynecologic health care for the adolescent solid organ transplant recipient

The improved survival of pediatric recipients of solid organ transplants has prompted increased attention to quality of life issues. These include attainment of normal growth, involvement in romantic relationships, and the desire to control fertility. As an increasing number of adolescent transplant recipients are involved in normal social and sexual relationships, they require careful attention to their gynecologic and reproductive health care needs. Anticipating the onset of sexual activity before it occurs may help to prevent a mistimed pregnancy by providing or prescribing condoms and emergency contraception in advance. In addition, many transplant recipients can safely use the currently available methods of hormonal contraception provided there is careful attention to organ function, other medical problems, and concurrently prescribed medications. In adolescent patients, issues such as pubertal development and menstruation, contraception, and routine gynecologic health care are typically addressed by the patient's primary care provider. However, the complexity of the adolescent transplant recipient's medical care necessitates close collaboration among all health care providers caring for the patient. This review is intended to help the transplant team better understand the gynecologic health care needs and treatment options of their adolescent patients.     

Bordetella bronchiseptica infection in pediatric lung transplant recipients

Bordetella bronchiseptica are small, pleomorphic Gram-negative coccobacilli which are commensal organisms in the upper respiratory tract of many wild and domestic animals ('kennel cough' in dogs). While it is common for health care providers to ask about exposure to ill family/friends, most do not routinely inquire about the health or immunization status of household pets. We report two cases of B. bronchiseptica pneumonia in lung transplant recipients [cystic fibrosis (CF); ages 10 and 15 yr; one male] who contracted B. bronchiseptica from pet dogs. We compared their course and outcome to four children (two CF, one congenital heart disease and one Duchenne's muscular dystrophy; four males, age range 6 months to 14 yr) with B. bronchiseptica cultured from the respiratory tract. Two of the four patients also acquired their illnesses from pet dogs and two from unknown sources. One lung transplant recipient expired from progressive respiratory failure. We conclude that B. bronchiseptica can cause serious infections in both immunosuppressed and immunocompetent children. We speculate that a detailed history of exposure to ill pets (particularly dogs), and the immunization status of all pets should be included in the routine evaluation of all pediatric transplant recipients.     

Multicenter data to improve health for pediatric renal transplant recipients in North America: Complementary approaches of NAPRTCS and IROC

Kidney transplantation increases life expectancy and improves quality of life for children with end‐stage kidney disease, yet sequelae of transplantation and treatment make it difficult for transplant recipients to enjoy health and quality of life similar to their healthy peers. The NAPRTCS network was among the first to use multicenter data to inform improvements in care and outcomes for children with a kidney transplant through observational research. Now, with new technologies and unprecedented access to data, it is possible to create learning health systems as envisioned by the US National Academy of Sciences to seamlessly integrate research and continuous improvement of clinical care. In this review, we present two pre‐eminent North American networks focused on using multicenter data to drive improved care and outcomes for children with a kidney transplant. Whereas, for the past 30 years NAPRTCS has focused on discovery of best practices through observational research and clinical trials, the Improving Renal Outcomes Collaborative, established in 2016, engages patients, families, clinicians, and researchers in redesigning the healthcare delivery system to enable practice change and continuous improvement of health outcomes. We discuss the history and past contributions of these networks, as well as current activities, barriers, and potential future solutions to more fully realize the vision of a true learning health system for pediatric kidney transplant recipients.     

What makes a good pediatric transplant lung: Insights from in vivo lung morphometry with hyperpolarized 3He magnetic resonance imaging

Obtaining information on transplanted lung microstructure is an important part of the current care for monitoring transplant recipients. However, until now this information was only available from invasive lung biopsy. The objective of this study was to evaluate the use of an innovative non‐invasive technique, in vivo lung morphometry with hyperpolarized ³He MRI—to characterize lung microstructure in the pediatric lung transplant population. This technique yields quantitative measurements of acinar airways’ (alveolar ducts and sacs) parameters, such as acinar airway radii and alveolar depth. Six pediatric lung transplant recipients with cystic fibrosis underwent in vivo lung morphometry MRI, pulmonary function testing, and quantitative CT. We found a strong correlation between lung lifespan and alveolar depth—patients with more shallow alveoli were likely to have a negative outcome sooner than those with larger alveolar depth. Combining morphometric results with CT, we also determined mean alveolar wall thickness and found substantial increases in this parameter in some patients that negatively correlated with DLCO. In vivo lung morphometry uniquely provides previously unavailable information on lung microstructure that may be predictive of a negative outcome and has a potential to aid in lung selection for transplantation.