Successful renal transplantation following prior bone marrow transplantation in pediatric patients

Improving survival rates following pediatric bone marrow transplantation (BMT) will likely result in greater numbers of children progressing to end-stage renal disease (ESRD) because of prior chemotherapy, irradiation, sepsis, and exposure to nephrotoxic agents. Renal transplantation remains the treatment of choice for ESRD; however, the safety of renal transplantation in this unique population is not well established. We report our experience with living related renal transplantation in three pediatric patients with ESRD following prior BMT. Two patients with neuroblastoma and ESRD because of BMT nephropathy, and one patient with Schimke immuno-osseous dysplasia and ESRD because of immune complex mediated glomerulonephritis and nephrotic syndrome. Age at time of BMT ranged from 2 to 7 yr. All patients had stable bone marrow function prior to renal transplantation. Age at renal transplant ranged from 8 to 14 yr. All three patients have been managed with conventional immunosuppression, as no patient received a kidney and BMT from the same donor source. These patients are currently 7 months to 6 yr status post-living related transplant. All have functioning bone marrow and kidney transplants, with serum creatinine levels ranging 0.6-1.2 mg/dL. There have been no episodes of rejection. One patient with a history of grade III skin and grade IV gastrointestinal-graft-vs.-host disease (GI-GVHD) prior to transplantation, had a mild flare of GI-GVHD (grade I) post-renal transplant and is currently asymptomatic. The incidence of opportunistic infection has been comparable with our pediatric renal transplant population without prior BMT. One patient was treated for basal cell carcinoma via wide local excision. Renal transplantation is an excellent option for the treatment of pediatric patients with ESRD following BMT. Short-term results in this small population show promising patient and graft survival, however long-term follow-up is needed. Pre-existing immune system impairment and bone marrow function should be taken into consideration when weighing different immunosuppressive agents for renal transplantation. Patients who have undergone renal transplantation following BMT are at high risk for opportunistic infections and malignancy, and need life-long medical surveillance.     

An overview of pediatric peritoneal dialysis and renal replacement therapy in infants: A review for the general pediatric surgeon

Currently, there are about 10,000 pediatric patients in the United States who rely on dialysis for renal replacement therapy. Dialysis allows children with chronic kidney disease a means of support until renal transplant is feasible. All forms of renal replacement therapy require a surgical intervention, whether the modality is hemodialysis or peritoneal dialysis. Despite peritoneal dialysis being the most common modality of dialysis in children, there is not prospectively collected much evidence in the literature which can guide the pediatric surgeon about best practices on access placement, management of complications, and timing of removal. Most available studies are small, single-center retrospective reviews. This limits the power of the data collected to help guide decision-making in the management of peritoneal dialysis catheters.The purpose of this review is to provide a consolidated source of best available evidence and identify important areas for future study. Furthermore, this is an area of pediatric surgical care that lacks up to date outcomes research with robust surgeon participation. Lack of coordinated, evidence-based best practices likely results in heterogenous surgical practices and uneven strategies for managing complications. Furthermore, with improvements in neonatal critical care and fetal interventions available for obstructive uropathies and other congenital kidney disorders, there is increased likelihood of the need for dialysis access in more infants, who represent a particularly vulnerable patient population. Importantly, peritoneal dialysis access should be instituted into the national PEDScore curriculum for pediatric surgical fellows, as this procedure is common enough that any pediatric surgeon could be consulted for catheter placement and management. Surgeon awareness of, and participation in the formulation, of guidelines and prospective studies is of paramount importance to ensure optimal care of this vulnerable population of children.     

Pediatric deceased donor renal transplantation: An approach to decision making I. Pediatric kidney allocation in the USA: The old and the new

Renal transplantation is the treatment of choice for children with end‐stage renal disease. More than 50% of children receive a deceased donor renal transplant. Marked disparity between the number of children on the renal transplant wait list and the supply has prompted numerous advances to increase supply as well as maximize the utility of donor organs. Allocation of deceased donor kidneys is based on several criteria. The organ allocation system policy is continually evaluated and changed incrementally to optimize allocation. We, in the United Sates, are in the process of transitioning into a new kidney allocation system to enhance post‐transplant survival benefit, increase utilization of donated kidneys, and increase transplant access for biologically disadvantaged candidates. This review will provide a brief overview of the organ sharing system in the United States, compare the “old” and the “new” allocation system, and discuss the considerations for the pediatric nephrologist while accepting a deceased donor kidney for a particular pediatric patient.     

New approaches to the autosomal recessive polycystic kidney disease patient with dual kidney–liver complications

Improved neonatal medical care and renal replacement technology have improved the long‐term survival of patients with ARPKD. Ten‐yr survival of those surviving the first year of life is reported to be 82% and is continuing to improve further. However, despite increases in overall survival and improved treatment of systemic hypertension and other complications of their renal disease, nearly 50% of survivors will develop ESRD within the first decade of life. In addition to renal pathology, patients with ARPKD develop ductal plate malformations with cystic dilation of intra‐ and extrahepatic bile ducts resulting in CHF and Caroli syndrome. Many patients with CHF will develop portal hypertension with resulting esophageal varices, splenomegaly, hypersplenism, protein losing enteropathy, and gastrointestinal bleeding. Management of portal hypertension may require EBL of esophageal varices or porto‐systemic shunting. Complications of hepatic involvement can include ascending cholangitis, cholestasis with malabsorption of fat‐soluble vitamins, and rarely benign or malignant liver tumors. Patients with ARPKD who eventually reach ESRD, and ultimately require kidney transplantation, present a unique set of complications related to their underlying hepato‐biliary disease. In this review, we focus on new approaches to these challenging patients, including the indications for liver transplantation in ARPKD patients with severe chronic kidney disease awaiting kidney transplant. While survival in patients with ARPKD and isolated kidney transplant is comparable to that of age‐matched pediatric patients who have received kidney transplants due to other primary renal diseases, 64–80% of the mortality occurring in ARPKD kidney transplant patients is attributed to cholangitis/sepsis, which is related to their hepato‐biliary disease. Recent data demonstrate that surgical mortality among pediatric liver transplant recipients is decreased to <10% at one yr. The immunosuppressive regimen used for kidney transplant recipients is adequate for most liver transplant recipients. We therefore suggest that in a select group of ARPKD patients with recurrent cholangitis or complications of portal hypertension, combined liver–kidney transplant is a viable option. Although further study is necessary to confirm our approach, we believe that combined liver–kidney transplantation can potentially decrease overall mortality and morbidity in carefully selected ARPKD patients with ESRD and clinically significant CHF.     

Pediatric Transplant Grand Rounds. Pediatric kidney transplantation at Stanford

(1) We believe that we have achieved excellent graft survival with pediatric kidney transplantation because: (a) we have had no technical losses; (b) there have been no primary immunologic losses within 4 years following transplantation; (c) we have avoided ATN. (2) Our cyclosporine dosage has been greater than the average dosage reported by the NAPRTCS, and we believe that this has led to: (a) a low incidence of rejection episodes; (b) because of this, good 1 and 2 year average serum creatinine levels. (3) In the management of adult-sized kidneys in infants and small children I have discussed: (a) the rationale and strategy to prevent vascular thrombosis, ATN and primary non-function; (b) the importance of optimizing intravascular volume, as well as renal and aortic blood flow. (4) With regard to the management of congenital urologic abnormalities I have discussed: (a) the strategy to avoid unnecessary surgery and to avoid scar around the aorta and the vena cava, particularly in infants and small children; (b) my philosophy regarding the abnormal bladder and the successful use of the small defunctionalized urinary bladder. We believe that these have been the primary ingredients to the success we have seen. I also harken back and continue to practice the adage advanced by my former mentor Dr. Fred Belzer that 'no kidney is better than a bad kidney!' And this could not be more true than in pediatric kidney transplantation, where graft failure enhanced by suboptimal graft quality may potentially both cripple the child and shorten his/her life.     

Pediatric heart transplant

Pediatric heart transplantation has additional and unique aspects from standard pediatric heart surgery and adult heart transplantation. The purpose of this article is to review pediatric heart transplantation and special surgical considerations. The methods used by the authors involved reviewing the literature and surgical techniques surrounding this patient population and procedure. The article presents a general review of the topic including the history, current state, surgical approaches, post-operative management, and outcomes in this patient population.     

Liver transplantation in children

The results of liver transplantation has improved significantly in the last decade with one year survival figures close to 90% for children with chronic liver disease. This can be attributed to improvement in surgical techniques, better postoperative care and newer immunosuppresive drugs. As a result of this, increasing number of children are referred for transplantation with no significant increase in the number of solid organ donors. The earliest transplants in children were performed using organs from size matched pediatric donors. However, as the pediatric donor numbers were limited, liver reduction techniques were developed to transplant small children before deterioration. Increasing experience with reduced livers led to the development of split liver, living donor and auxiliary liver transplantation. Better management of immunosuppressive drugs and newer agents such as Mycophenolate Mofetil have reduced the incidence of graft loss due to chronic rejection and long-term renal toxicity. The goal for the future will remain to be transplantation without the use of longterm immunosuppression.     

Pediatric kidney transplantation

Since first performed in 1954, kidney transplantation has evolved as the preferred long-term treatment of children with end stage renal disease (ESRD). The etiology of chronic kidney disease (CKD) and ESRD in children is broad and can be quite complicated, necessitating a multidisciplinary team to adequately care for these patients and their myriad needs. Precise surgical techniques and modern protocols for immunosuppression provide excellent long-term patient and graft survival. This article reviews the many etiologies of renal failure in the pediatric population focusing on those most commonly leading to the need for kidney transplantation. The processes of evaluation, kidney transplantation, short-term and long-term complications, as well as long-term outcomes are also reviewed.     

“Inverted” positioning of renal allograft during kidney transplantation in children and adolescents: A single‐institution comparative analysis

Renal transplantation is the treatment of choice in children with end‐stage renal failure. Limitations in patient anatomy or a short donor renal vein may necessitate intraoperative inversion of the kidney. There is little evidence to support the use of this surgical technique, and no evidence in the pediatric population. This study identifies the perioperative and post‐operative outcomes of inverted renal transplants in pediatric patients. We reviewed all patients having a renal transplant between January 2012 and December 2016 and collected short‐ and long‐term outcomes of patients who received an inverted allograft. Early graft function was defined as the time to reach creatinine nadir. During this time, our hospital performed 81 transplants, and 50 (62%) were from deceased donors, including the 6 (12%) patients who received inverted renal grafts. Half (3/6) were female, 5/6 (83%) were dialysis‐dependent, and the median age at surgery was 13 years (range 9‐16 years). There was no significant difference in mean creatinine nadir values (P = 0.518) and the time to creatinine nadir mean values (P = 0.190) between the upright and inverted renal transplant groups. There were also no significant differences in rates of post‐operative complications between the upright and inverted allograft recipients. Inversion of renal allografts in pediatric patients is a viable surgical technique to compensate for shortcomings in patient anatomy or in special cases of renal transplantation involving a short donor renal vein. Future research should focus on outcomes of a larger group of pediatric inverted renal transplant patients.     

Overview of pediatric kidney transplantation

Kidney transplantation is the treatment of choice for pediatric patients with end-stage kidney disease. Unlike adult recipients undergoing transplantation, special considerations must be taken when transplanting children based on the underlying etiology of kidney disease, previous surgical procedures, anatomical limitations and necessary technical adjustments. Additionally, the choice of donor must be measured to ensure optimal graft survival given a longer post-transplant life expectancy. Those topics as well as frequently encountered postoperative complications are also discussed in this publication.     

Risk factors for febrile urinary tract infections in the first year after pediatric renal transplantation

Urinary tract infection is the most common infectious complication following kidney transplant. Anatomic abnormalities, bladder dysfunction, a positive history of febrile urinary tract infection, and recipient age are reported risk factors. The aim of this study was to determine the risk factors for fUTI, which necessitated hospitalization in the first year after renal transplantation in our pediatric transplant population. A retrospective review of 195 pediatric patients who underwent kidney transplant between 2008 and 2017 from a single institution was performed. All patients admitted to the hospital with fUTI were marked for further analyses. The risk factors including age, gender, dialysis type, history of urologic disorders, and preoperative proteinuria for fUTI in the first year after kidney transplantation and graft survivals were investigated. Independent‐sample t test and chi‐square tests were used for univariate analysis. Exhaustive CHAID algorithm was used for multivariate analysis. The data of 115 male and 80 female patients were retracted. The mean ages of our cohort for males and females were 9.5 ± 5.1 and 10 ± 4.8 years, respectively. The age of the patients at transplant and their gender were found to be a statistically significant risk factors for developing fUTIs. Multivariate analysis showed that fUTI was common in female patients and a subgroup of male patients who had preoperative proteinuria, but no neurogenic bladder had higher risk compared with male patients without proteinuria. Patient surveillance and antibiotic prophylaxis algorithms can be developed to prevent febrile urinary tract infections seen after pediatric kidney transplantation in risky population.     

Risk factors for cardiovascular disease in pediatric renal transplant recipients

About 1,000 children develop end-stage renal disease (ESRD) each year in the United States and about 5,000 children are currently receiving dialysis. Children who develop ESRD are eligible to receive renal replacement therapy, including renal transplantation. There are inherent risks associated with transplantation, including renal insufficiency, infections, post-transplant lymphoproliferative disorder, and cardiovascular disease (CVD). Potential risk factors for CVD in pediatric renal transplant recipients include renal insufficiency, hyperlipidemia, hyperhomocysteinemia, inflammation, malnutrition, anemia, and hyperglycemia/insulin resistance. Despite evidence that many children may possess various risk factors for CVD post-renal transplantation, there are very few studies that have attempted to assess the link between these risk factors and CVD in pediatric renal transplant recipients.     

Indications for pediatric liver transplantation

This review discusses the indications for orthotopic liver transplantation (OLT) in children and provides guidelines for the appropriate time to list children for transplant. The diseases for which OLT are indicated in children are divided into diagnostic categories with a focus on the natural history and appropriate medical and surgical therapy prior to transplantation. Contraindications to transplantation pertinent to specific diseases are outlined, with particular emphasis on complex metabolic defects with extrahepatic manifestations. The clinical conditions which indicate that listing for OLT is appropriate, as well as the relative and absolute contraindications, irrespective of diagnosis, are discussed. The importance of malnutrition and poor development as listing criteria is stressed. Special timing considerations for diagnoses relevant to the pediatric age group, e.g. urea cycle defects and Crigler-Najjar syndrome, are emphasized. Finally, the impact of co-existing extrahepatic disease on the decision to list children for OLT is reviewed.     

Pediatric renal transplantation: indications and special considerations. A position paper from the Pediatric Committee of the American Society of Transplant Physicians

Renal transplantation of children with chronic renal insufficiency (CRI) and end-stage renal disease (ESRD) appears to be the optimal form of renal replacement therapy. This report, which expresses the opinions of the nephrology members of the Pediatric Committee of the American Society of Transplant Physicians, discusses the indications for pediatric renal transplantation and identifies the unique aspects of caring for children with CRI and ESRD. Indications for pediatric renal transplantation include: 1) symptoms of uremia not responsive to standard therapy; 2) failure to thrive due to limitations in total caloric intake; 3) delayed psychomotor development; 4) hypervolemia; 5) hyperkalemia; and 6) metabolic bone disease due to renal osteodystrophy. The urgency and timing of renal transplantation in children must be considered in the context of a number of issues unique to children with CRI and ESRD such as delayed cognitive and educational performance, growth retardation, delayed puberty, etiology of ESRD, and timing of immunizations. In addition, these children frequently display various inherited and sporadic syndromes with multiorgan involvement requiring the expertise of a variety of pediatric subspecialists including the pediatric urologist, who plays a critical role in the evaluation of children with obstructive uropathy and other anomalies of the genito-urinary system. The advantages of a living-related donor are also delineated. The importance of adequate immunosuppression on graft function, early recognition of the signs and symptoms acute rejection, preventive strategies for minimizing the morbidity and mortality from viral infections in the post-transplant period, and the impact of transplantation on cognitive function, educational status, and catch-up growth are also discussed. To address these complex issues, transplant care of pediatric patients must be provided by a multidisciplinary team of pediatric health care professionals.     

Long-term care of pediatric renal transplant patients: from bench to bedside

In this review, we discuss current and future issues in the management of pediatric renal transplant recipients, including the optimization of long-term graft function and the minimization of complications caused by immunosuppression. Long-term management involves not only the monitoring of graft function but also the identification of patients at risk for the development of complications. The identification of patients with immunoreactive or immunoregulatory responses can be performed molecular monitoring of the immune response. Also, the use of frequent surveillance kidney biopsies, surrogate markers of chronic rejection, and glomerular filtration rate will be a part of future management. Identifying high-risk patients enables the physician to optimize immunosuppression to limit acute rejection. Short-and long-term management of pediatric transplant patients also includes adequate monitoring of growth and the monitoring for post-transplant lymphoproliferative disease. Ongoing clinical trials are underway that focus on these novel approaches in caring for pediatric transplant recipients.     

Renal transplantation in patients with Alport syndrome

For pediatric kidney transplant physicians, two aspects of Alport syndrome set the disease apart from other causes of terminal renal failure. First, an understanding of the genetics of Alport syndrome is needed to make appropriate decisions regarding potential related kidney donors to Alport patients requiring renal transplantation. Second, renal transplantation for Alport syndrome may be complicated by post-transplant anti-GBM nephritis, a problem that is nearly unique to this disease. This review discusses these aspects of Alport syndrome and attempts to provide rational recommendations for clinicians.     

Detection of polyomavirus BK and JC in children with kidney diseases and renal transplant recipients

BACKGROUND: Reactivation of polyomavirus is a known reason for severe renal dysfunction in adult renal transplant recipients. Testing for polyomavirus DNA in plasma has been described as a sensitive and specific method to discover viral nephropathy in adult patients. We were now interested in polyomavirus status in a pediatric patient setting. METHODS: Plasma and urine samples were obtained from 80 children including 38 children after renal transplantation (group 1), 7 children with different kidney diseases receiving immunosuppressive treatment (group 2) and 35 children with different kidney diseases not receiving immunosuppressive treatment (group 3). A nested polymerase chain reaction method was used for amplification of polyomavirus DNA fragments. Differentiation between JC and BK virus was done by digestion with restriction endonucleases. RESULTS: Polyomavirus DNA was detected in the urine sample of 19 of 38 (50%) renal transplant recipients (group 1), of 1 of 7 (14%) patients from group 2 and in none of the 35 patients of group 3. Plasma samples from 3 (8%) of group 1 patients and from 1 child each of group 2 (14%) and group 3 (3%) were tested positive for polyomavirus DNA. CONCLUSION: Urinary polyomavirus excretion seems to be more frequent in pediatric patients with kidney diseases receiving immunosuppressive treatment and after renal transplantation than in children with various kidney diseases without immunosuppressive treatment.     

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.     

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.     

Chronic hemodialysis in pediatric patients: technical and practical aspects of use

Chronic kidney disease (CKD) is a continuum of progressive reduction in kidney function lasting for more than three months, due to either structural and/or functional renal abnormalities that may lead to irreversible kidney damage. The term "renal supportive therapy" (RST) generally characterizes the spectrum of dialysis therapies available to support existing renal function in patients with CKD during progression to end-stage renal disease (ESRD) and/or renal transplantation. Chronic RST modalities include conventional hemodialysis, peritoneal dialysis and home hemodialysis therapies. The modality chosen to deliver RST in the pediatric patient is often guided by a variety of factors including institutional resources, local expertise, patient characteristics, treatment goals, and physician preference. Chronic RST in a pediatric population requires the flexible utilization of multiple delivery modalities for effective care across infancy into adulthood and is not typically initiated until GFR declines to between 15-30 mL/min per 1.73 m2, although thresholds for initiation of RST will vary between patients. This review will provide an overview of current approaches to management and technical approaches to pediatric patients requiring chronic hemodialysis.