North American Pediatric Renal Transplant Research Articles

Left ventricular hypertrophy in pediatric patients on maintenance dialysis: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Cardiovascular disease is the leading cause of death in pediatric patients with kidney failure. Left ventricular hypertrophy (LVH) is recognized as the most common cardiovascular abnormality in these patients. There remains a paucity of longitudinal studies evaluating LVH during maintenance dialysis in children. NAPRTCS has collected echocardiographic data of pediatric maintenance dialysis patients since 2013 and is one of the largest registries to assess longitudinal changes in LVH. Patients aged 1-18years with echocardiographic data and without underlying structural cardiovascular diseases were included. LVH was defined as left ventricular mass index (LVMI, height-indexed) > 95th percentile for age and sex. Univariate and multivariable logistic regression was performed to assess risk factors for LVH at baseline. Generalized estimating equation was used to assess risk factors of changes in LVH during maintenance dialysis. A total of 518 patients had echocardiographic data available for analysis during time on maintenance dialysis. Of 179 patients with baseline echocardiography (within 30days of dialysis initiation), 67% had LVH. In multivariable logistic regression adjusted for age, race, and sex, uncontrolled hypertension (OR 9.4, 95% CI 2.8-31) and anemia (OR 2.3, 95% CI 1.0-5.3) were associated with LVH at baseline. Prevalence of LVH remained high at 40-50% during follow-up. Controlled and uncontrolled hypertension as well as phosphorus level were independently associated with increased likelihood of LVH during maintenance dialysis. LVH is prevalent in pediatric patients at dialysis initiation and remains prevalent during follow-up. Hypertension is the strongest risk factor for LVH in children on maintenance dialysis. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinical outcomes and survival in pediatric patients initiating chronic dialysis: a report of the NAPRTCS registry.

The 2011 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry comprises data on 6482 dialysis patients over the past 20years of the registry. The study compared clinical parameters and patient survival in the first 10 years of the registry (1992-2001) with the last decade of the registry (2002-2011). There was a significant increase in hemodialysis as the initiating dialysis modality in the most recent cohort (42% vs. 36%, p<0.001). Patients in the later cohort were less likely to have a hemoglobin <10g/dl [odds ratio (OR) 0.68; confidence interval (CI) 0.58-0.81; p<0.001] and height z-score <2 standard deviations (SD) below average (OR 0.68, CI 0.59-0.78, p<0.0001). They were also more likely to have a parathyroid hormone (PTH) level two times above the upper limits of normal (OR 1.39, CI 1.21-1.60, p<0.0001). Although hypertension was common regardless of era, patients in the 2002-2011 group were less likely to have blood pressure >90th percentile (OR 1.39, CI 1.21-1.60, p<0.0001), and a significant improvement in survival at 36months after dialysis initiation was observed in the 2002-2011 cohort compared with the 1992-2001 cohort (95% vs. 90%, respectively). Cardiopulmonary causes were the most common cause of death in both cohorts. Young age, growth deficit, and black race were poor predictors of survival. The survival of pediatric patients on chronic dialysis has improved over two decades of dialysis registry data, specifically for children <1year.

Solid tumors following kidney transplantation in children

Kidney transplant recipients have an increased risk of cancer. Data on non-LPD malignancies (solid tumors) in pediatric renal transplant recipients are limited. We performed a cohort study using the NAPRTCS transplant registry to describe the incidence of non-LPD malignancy compared with the general pediatric population. The observed incidence rate of non-LPD malignancy in the NAPRTCS transplant registry was 72.1 per 100,000 person-years (SIR 6.7; 95% CI, 5.3, 8.5); a 6.7-fold increased risk compared with the general pediatric population (10.7 cases per 100,000 person-years). Non-LPD malignancy was diagnosed in 35 subjects at a median of 726 days post-transplant. The most common type of malignancy was renal cell carcinoma. The increased risk of non-LPD malignancy was seen in all patients regardless of age, gender, race, etiology of end-stage kidney disease, and transplant era. The specific type of immunosuppression was not identified as a risk factor. In this first large-scale study of North American pediatric renal transplant recipients, we observed a 6.7-fold increased risk of non-LPD malignancy compared with the general pediatric population. Further examination of this unique patient population may provide greater insight into the impact of transplant and immunosuppression on malignancy risk.

Bradykinin receptor 1 activation exacerbates experimental focal and segmental glomerulosclerosis

Focal and segmental glomerulosclerosis (FSGS) is one of the most important causes of end-stage renal failure. The bradykinin B1 receptor has been associated with tissue inflammation and renal fibrosis. To test for a role of the bradykinin B1 receptor in podocyte injury, we pharmacologically modulated its activity at different time points in an adriamycin-induced mouse model of FSGS. Estimated albuminuria and urinary protein to creatinine ratios correlated with podocytopathy. Adriamycin injection led to loss of body weight, proteinuria, and upregulation of B1 receptor mRNA. Early treatment with a B1 antagonist reduced albuminuria and glomerulosclerosis, and inhibited the adriamycin-induced downregulation of podocin, nephrin, and α-actinin-4 expression. Moreover, delayed treatment with antagonist also induced podocyte protection. Conversely, a B1 agonist aggravated renal dysfunction and even further suppressed the levels of podocyte-related molecules. Thus, we propose that kinin has a crucial role in the pathogenesis of FSGS operating through bradykinin B1 receptor signaling.

A guideline for the inpatient care of children with pyelonephritis

BACKGROUND AND OBJECTIVES:Febrile urinary tract infections and pyelonephritis are common in children and frequently lead to hospitalization for management, especially in the child who appears toxic. The American Academy of Pediatrics (AAP) practice parameter on the diagnosis, treatment and evaluation of the initial urinary tract infection in febrile infants and young children provides experience and evidence-based guidelines for the practitioner caring for children between the ages of 2 months to 2 years. No established guideline exists for older children and the AAP guideline does not specifically focus on inpatient care.METHODS:We conducted a comprehensive review of recently published literature and practice guidelines to develop a consensus on the inpatient diagnosis and management of children with pyelonephritis.RESULTS:Eight recommendations are proposed for the diagnosis and management, including revised guidelines for the imaging studies postpyelonephritis on the basis of current best evidence.CONCLUSION:Proper diagnosis of pyelonephritis, timely initiation of appropriate therapy and identification of children at risk for renal injury will help to reduce immediate as well as long-term complications due to chronic kidney disease.

Is Retroperitoneoscopy the Gold Standard for Endoscopic Nephrectomy in Children on Peritoneal Dialysis?

The literature on minimally invasive nephrectomy in adults and children on peritoneal dialysis is sparse. Case reports suggest that the transperitoneal approach is effective. We present our experience with retroperitoneoscopic nephrectomy in children on peritoneal dialysis. At 11 consecutive retroperitoneoscopic nephrectomies a total of 14 kidneys were removed from 10 children with a mean age of 12 years. We used a 3-port lateral retroperitoneoscopic nephrectomy technique with active trainee participation. Preoperative and postoperative biochemistry results within 3 months of surgery were compared with the Wilcoxon signed rank test. Three bilateral synchronous, 1 bilateral staged and 6 unilateral retroperitoneoscopic nephrectomies were done. Mean operative time was 174 minutes for unilateral and 458 minutes for bilateral nephrectomy, including 1 simultaneous peritoneal dialysis insertion and 1 umbilical hernia repair. No open conversion, blood transfusion or postoperative surgical complication was noted. Peritoneal dialysis was initiated at a median of 9 hours postoperatively and dialysate volume was titrated to target within a median of 60 hours. One patient with a small peritoneotomy needed temporary hemodialysis despite intraoperative airtight repair. After surgery median serum albumin increased from 30.0 to 34.3 gm/l. Retroperitoneoscopic nephrectomy for end stage renal disease is a safe, effective technique that preserves peritoneal integrity in children who require immediate postoperative peritoneal dialysis. Avoiding post-nephrectomy hemodialysis decreases patient morbidity, preserving vessels for future vascular access. Compared to the literature on laparoscopy in this setting, retroperitoneoscopic nephrectomy can be considered the ideal approach for minimally invasive nephrectomy in patients on peritoneal dialysis.

What have 20 years of data from the North American Pediatric Renal Transplant Cooperative Study taught us about growth following renal transplantation in infants, children, and adolescents with end-stage renal disease?

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.

Varicella Zoster Virus (VZV) in Solid Organ Transplant Recipients

-herpesvirus family. VZV is presentworldwide and is highly infectious. Primary infection leadsto acute varicella or ‘chickenpox,’ usually from exposureeither through direct contact with a skin lesion or throughairborne spread from respiratory droplets (1,2). After initialinfection, VZV establishes lifelong latency in cranial nerveanddorsalrootganglia,andcanreactivateyearstodecadeslater as herpes zoster (HZ) or ‘shingles’ (3). More than90% of adults in the United States acquired the disease inchildhood, while the majority of children and young adultshave been vaccinated with the live virus vaccine (2,4).Primary varicella typically presents with fever, constitu-tional symptoms and a vesicular, pruritic, widely dissem-inated rash that primarily involves the trunk and face (5).Thesymptomsusuallyresolvewithin7–10days,butinrarecases primary varicella leads to more severe disease andvisceral invasion. Complications, such as hepatitis, pancre-atitis, pneumonitis and encephalitis are infrequent but canbelife-threatening;adultsandveryyoungchildrenaremorelikely to develop such complications from primary infection(6,7). Rates of hospitalization and mortality due to varicellahave dropped with the institution of routine childhood vari-cella vaccination (8,9).Nearly all patients with HZ develop an exanthem of vesic-ular lesions in a dermatomal distribution. The annual inci-dence of HZ in the general population is 1.5–3.0 cases per1000 persons (2), and is estimated to occur in up to 20%of individuals during their lifetime (10). Secondary compli-cations such as bacterial superinfection and postherpeticneuralgia (PHN), or chronic neuropathic pain at the site ofHZ, lead to increased morbidity (11).Over 90% of adult solid organ transplant (SOT) recipientswill be seropositive for VZV. Rates are lower in pediatrictransplants(12,13),butimmunitywillincreaseasuptakeofvaricella vaccine improves. Varicella is rare in adult SOT re-cipients,butcanbedevastating,withvisceralinvolvement,severe skin disease, and disseminated intravascular coag-ulation (14–19). HZ is a frequent infectious complication inSOT recipients with an incidence of approximately 8–11%during the first 4 years posttransplant (20–22). Invasive dis-ease and dissemination similar to that seen in primary VZVinfection are uncommon but have been reported in SOTand other immunocompromised populations, and level ofimmunosuppression may alter the risk of developing thesecomplications (17,23,24). Rates of PHN in SOT recipi-ents may also be higher than in immunocompetent popu-lations (22).

Notice of release of La Salle germplasm Arizona cottontop selected class of natural germplasm

ABSTRACT. Hypertension frequently complicates the course of chronic renal insufficiency (CRI) in children. This study sought to define the role of hypertension in progression of CRI in children by using the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) CRI database. The study cohort consisted of 3834 patients aged 2 to 17 yr with an estimated GFR (eGFR) ≤75 ml/min·1.73 m² enrolled onto NAPRTCS. The time to end point was defined as the time between registry enrollment and progression to renal substitution therapy or a 10 ml/min·1.73 m² drop in GFR from baseline, whichever was first. Forty-eight percent of the study patients had hypertension at baseline. There was a significant difference in reaching end points between hypertensive and normotensive children (58% <i>versus</i> 49%, respectively, <i>P</i> &lt; 0.001). Significant difference in outcome between hypertensive and nonhypertensive patients was seen in children with eGFR 50 to 75 ml/min·1.73 m² (<i>P</i> &lt; 0.001). Multivariate Cox regression modeling demonstrated that systolic hypertension was a significant independent predictor of progression of CRI (<i>P</i> = 0.003). Other significant predictors of CRI progression in this model included older age (<i>P</i> = 0.0001), African American ethnicity (<i>P</i> = 0.03), acquired cause of renal disease (<i>P</i> = 0.0001), and baseline eGFR &lt;50 ml/min·1.73 m² (<i>P</i> = 0.0001). Hypertension is a highly significant and independent predictor for progression of CRI in children. E-mail: Mark.Mitsnefes@cchmc.org

Renal allograft thrombosis

Early graft thrombosis Renal allograft thrombosis may be responsible for 2–7% of early allograft losses in adults [1] and up to 35% in children [2]. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) reported that graft thrombosis represented the main cause of graft failure in the first year. Most cases of renal allograft thrombosis occur early in the postoperative period with a peak incidence of 48 h. However, thrombus formation may be delayed until after the first week [3]. Thrombosis may initially involve the renal artery or more frequently the renal vein, but in some cases it is difficult to ascertain where the thrombosis originated. Several factors may be involved in the pathogenesis of graft thrombosis. Thrombosis may be caused by technical errors, by vascular clamp injury or perfusion cannulation injury. Although vascular abnormalities in the donor kidney may be responsible for graft thrombosis [4] (thrombosis is reported in up to 36% of allografts with multiple renal arteries), however, in a multivariate analysis, the presence of atheroma was the only independent factor associated with the risk of arterial renal thrombosis [5]. Paediatric transplant recipients of kidneys from cadaver donors <5 years of age had a significantly higher thrombosis rate than did recipients from older donors [6]. This increased risk is attributable to the discrepancy in the size between the vessels of the donor and the recipient. In the past, cases of arterial thrombosis have been reported with cadaveric paediatric ‘en bloc’ transplantation. Recent results with this technique are excellent with no vascular thrombosis [7,8].

Universal Thrombophilia Screening with Risk Stratification and Anticoagulation Management in Pediatric Renal Transplant Recipients.

Objective To identify renal transplant patients at a higher risk for allograft thrombosis and develop a risk stratification protocol for post-operative anticoagulation.Background According to the North American Pediatric Renal Transplant Cooperative Study data, vascular thrombosis is responsible for 12% of renal transplant failures. Congenital and acquired prothrombotic disorders have recently been found to play a major role in defining outcome of the renal transplants.Methods In 2007, we initiated universal screening for acquired and congenital thrombophilic risk factors for all renal transplant patients prior to transplant. They were assigned a risk category (Level I-IV) based on the presence of thrombophilic risk factors and their post-operative anticoagulation plan was pre-determined based on their risk level (Table). Low-dose unfractionated heparin drip was initiated a few hours after the transplant and titrated to achieve a 1.5 fold aPTT level. Anticoagulation was changed to low molecular weight heparin (LMWH) on day 2–4, when the risk of major bleed was over, and the serum creatinine had normalized.Result Nine patients have been screened and 8/9 were found to be at high risk for thrombosis (Level II or III). The prothrombotic risk factors identified were Prothrombin gene mutation (2), MTHFR (8), Lupus anticoagulant (2) and low protein S (2). Five patients have undergone renal transplant, and have been treated with LMWH post-operatively as per plan, with successful outcome. No patient has developed allograft thrombosis. 1/5 patients developed a peri-renal hematoma requiring evacuation, but completed prophylactic LMWH therapy.Conclusion Renal allograft thrombosis is preventable. Universal screening can stratify risk and allow an effective intervention to reduce that risk. Our Institution has developed a unique risk stratification protocol to identify patients at high risk for allograft thrombosis and prevent this complication by post-operative anticoagulation.Risk Categorization and Management PlanRisk LevelThrombophiliaManagementLevel IEvidence of Thrombophilia (other than MTHFR) and previous thrombosisHeparin postoperatively and then LMWH bid for 6 monthsLevel IIEvidence of Thrombophilia (other than MTHFR), No history of thrombosisHeparin postoperatively, LMWH bid for 3 months, then qd for 3 monthsLevel IIIMTHFR with normal homocysteineHeparin postoperatively, then LMWH qd for 3 monthsLevel IVNo evidence of thrombophiliaNo anticoagulation

Decreased Incidence of Acute Rejection in Adolescent Kidney Transplant Recipients Using Antithymocyte Induction and Triple Immunosuppression

Acute rejection is a frequent event in pediatric renal transplantation; it can diminish allograft function and affect long-term outcome. Recent data from the North American Pediatric Renal Transplant Cooperative Study indicates that the rate of acute rejection remains high despite current immunosuppressive regimens. In this retrospective series, we examined 37 pediatric renal transplant recipients who received induction doses of antithymocyte globulin combined with maintenance immunotherapy using tacrolimus, mycophenolate mofetil, and prednisone. The postoperative course was reviewed for initial and total hospital stay, number of rehospitalizations, evidence of posttransplant complications, graft fibrosis, and overall patient and graft survival. Three episodes of acute rejection (8.1%) were recorded in the first year posttransplant. The median initial hospital stay for patients receiving a kidney transplant was 8 days. Patient and graft survival were 100% and 91.9% at 1 year, respectively. The incidence of viral infection (cytomegalovirus, BK virus, and Epstein-Barr virus) and posttransplant lymphoproliferative disease remained low. Urinary tract infection and fluid and electrolyte complications were the main causes of posttransplant hospitalization. We conclude that induction with antithymocyte globulin and maintenance immunosuppression with tacrolimus, mycophenolate, and prednisone should be considered a valuable tool in the management of children undergoing renal transplantation.

Younger Age and Antibody Induction Increase the Risk for Infection in Pediatric Renal Transplantation: A NAPRTCS Report

Infections now exceed rejection as a cause of hospitalization in the first 2 years post-renal transplantation. We analyzed data from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) to determine risks for hospitalization for infection (HI), either bacterial (HBI) or viral (HVI). 3106 children transplanted between 1996 and 2002 with 2-year follow-up were analyzed. Univariate and multivariate logistic regression analyses identified factors for cause-specific hospitalization. 23.4% experienced HBI, 23.9% HVI; 8.9% were hospitalized for both. Children 0-1 years age at transplant had higher rates of HI (64.2%), HBI (40.3%) and HVI (43.3%) compared to >12 years (31%, 17.5% and 18.9%, p < 0.0001). In comparison to no induction, patients receiving monoclonal or polyclonal antibody were more likely to have HI (>42% vs. 34.0%), HBI (>24% vs. 21%) or HVI (>29% vs. 21%, all p < 0.003) but had equivalent graft survival (p = NS). Higher rates of HI, HBI and HVI were also seen with prophylactic antimicrobial use and with >5 transfusions pretransplant. Since antibody induction in recent era was not associated with better graft or patient survival but was associated with more HI and HVI, the need for routine antibody induction in children needs to be reassessed.

Recovery and Utilization of Deceased Donor Kidneys from Small Pediatric Donors

To the Editor: We appreciate the comments by Dr. Martin et al. on our recent manuscript (1Pelletier SJ Guidinger MK Merion RM et al.Recovery and utilization of deceased donor kidneys from small pediatric donors..Am J Transplant. 2006; 6:: 1646-1652Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar). In their letter, they highlight the idea that kidneys from small pediatric deceased donors may be underutilized. We agree that a more aggressive approach to the recovery and utilization of kidneys from this population would be appropriate. They describe some of the technical challenges that may be encountered, particularly with the smallest of donors, which have led some transplant centers to avoid using these grafts. However, as described by Martin et al., many of these difficulties can be overcome and our analysis of national data suggests that excellent graft function can be achieved. Because not all recipient patient populations may benefit equally from en bloc kidney transplantation from small pediatric donors, appropriate recipient selection is important. The North American Pediatric Renal Transplant Cooperative Study demonstrated a considerably increased rate of graft thrombosis for pediatric recipients receiving kidney transplants from donors under 5 years old (2Singh A Stablein D Tejani A Risk factors for vascular thrombosis in pediatric renal transplantation: A special report of the North American Pediatric Renal Transplant Cooperative Study..Transplantation. 1997; 63:: 1263-1267Crossref PubMed Scopus (200) Google Scholar). The current data do not support the transplant of small pediatric donor kidneys into small pediatric recipients. The optimal use of kidneys from small pediatric deceased donors remains unclear. Further studies are needed to determine when kidneys from this donor population should be transplanted individually, benefiting a greater number of recipients, as opposed to transplantation en bloc, where results are maximized for an individual recipient. The Scientific Registry of Transplant Recipients is funded by contract number 231-00-0116 from the Health Resources and Services Administration, U.S. Department of Health and Human Services. The views expressed herein are those of the authors and not necessarily those of the U.S. Government.

Epidemic of Childhood Obesity: Implications for Kidney Disease

Childhood obesity has become a global epidemic. Childhood obesity has many long-term adverse effects on morbidity and mortality. The prevalence of end-stage renal disease (ESRD) has risen dramatically in the past decade in parallel with the increase in obesity. Our current understanding of the consequences of childhood obesity on kidney function and disease is very limited. The present study presents the worldwide trends in childhood obesity and reviews published studies that have examined the association between obesity and kidney disease in the pediatric and adult populations. A large number of studies have been conducted to examine the association between obesity and kidney disease in general adult populations; however, few have been conducted to examine the impact of childhood obesity on the risk of kidney disease. Findings from large cohort studies in adult general populations show that obesity increases the risk of kidney diseases. Six follow-up studies in pediatric patients were identified, and they indicate that childhood obesity is associated with an increased risk of kidney disease and the progression and mortality of kidney disease. Future studies in the pediatric populations are needed.

Renal Transplantation in Children 15 Kg or Less: The British Columbia Children’s Hospital Experience

Small infants are the most challenging group of patients to undergo renal transplantation. We reviewed the transplantation experience at our institution with children less than 15 kg at transplantation. We retrospectively reviewed the records of 24 recipients in a 20-year period. Technical and allograft outcomes were compared to those in the North American Pediatric Renal Transplant Cooperative Study database. Since the inception of our program 24 recipients weighing 15 kg or less who were 6 years or younger have undergone transplantation. Seven grafts (29%) were from living donors. At transplantation mean age was 3.1 years (range 1.8 to 5.7) and mean weight was 13.4 kg (range 9.0 to 15.7). Average cold and warm ischemic times were 14.1 hours (range 3.4 to 37.2) and 23.1 minutes (range 21 to 41), respectively. Early complications were ureteral stricture requiring pyeloureterostomy in 1 case, reversible acute tubular necrosis in 2 and early arterial thrombosis salvaged by immediate thrombectomy in 1. Delayed complications were arterial stenosis requiring angioplasty in 2 cases, and 3 delayed deaths related to malignant hypertension in 2 and sepsis in 1. No grafts were lost due to thrombosis. Mean serum creatinine at years 1 to 3 and 5 were 48.5, 67.5, 79.1 and 84.4 mumol/l, respectively. Graft survival was 92% (22 patients after censoring 1 who died with a functioning graft) at 2 and 5 years. Overall results compare favorably to those in the North American Pediatric Renal Transplant Cooperative Study. With a multidisciplinary team effort successful results can be achieved in this challenging group of patients.

Protocol biopsies should not (yet) be the standard of care in pediatric renal transplant recipients

The care and management of renal transplant recipients, and especially of pediatric renal transplant recipients, is potentially complex and exacting. Balancing the amount of immunosuppression to prevent toxicity and to avoid rejection is not always straightforward. In addition, the specific needs of pediatric patients add another layer of complexity to their care. A reasonable question is whether routine protocol kidney biopsies (by definition, in patients with stable renal function) will help to optimize the management of pediatric kidney recipients, and whether the benefits justify making them the standard of care for all pediatric kidney recipients. I would argue that they do not, and that protocol biopsies should not yet be performed routinely in all patients. There is no question that obtaining renal allograft biopsies to evaluate renal dysfunction is essentially mandatory. Without a biopsy to establish the diagnosis, any therapeutic intervention is a poorly educated guess. However, the use of invasive biopsies to evaluate all children with stable renal function is another matter. It is certainly possible, even likely, that such biopsies, preferably in combination with mechanistic studies of immunologic reactivity, represent important research tools. They can reveal whether important subclinical events are occurring that can impact on long-term patient and graft survival. Such studies should be performed in selected centers with the manpower and expertise to perform protocol biopsies safely and routinely. It is even reasonable for a given center to consider them as its standard of care. At issue is whether the results from studies that have performed protocol biopsies justify their expansion to every pediatric kidney transplant program. There is a fairly substantial literature on protocol biopsies in adult renal transplant recipients, and a smaller literature on pediatric recipients. These studies show a variable incidence of subclinical acute rejection, ranging from 2.6–100%, with many reports in the 25–30% range (1–18). There is also a literature demonstrating an incidence of subclinical chronic allograft nephropathy (CAN) (6, 8, 10, 13, 14, 17–25), and a suggestion that the presence of CAN with vasculopathy is a poor prognostic factor for long-term outcome (8). However, the important issue in protocol biopsies is whether performing them will lead to management changes that will improve long-term graft survival and function. The only randomized trial that has demonstrated a benefit to diagnosing and treating subclinical acute rejection is the adult Winnipeg experience and, while it is persuasive, it is a relatively small, single center experience (3–6). The pediatric protocol biopsy experience from Winnipeg, which was not randomized, was associated with excellent three-yr graft survival and renal function, but was associated with an incidence of CAN of 86%, despite the aggressive treatment of subclinical rejection (26). While the risks of protocol biopsies are low, they are not zero. Substantial morbidity, and even mortality, has been associated with kidney transplant biopsies; fortunately, these catastrophic complications are rare (12, 27). In patients with an indication for a biopsy, the low risk is justified by the benefit of knowing the cause of the renal dysfunction. In a protocol biopsy setting, it is a reasonable question to ask whether the risk is justified. By making protocol biopsies the standard of care in all programs, there is an increased risk of a serious biopsy-related adverse event, especially in centers without the infrastructure and expertise to perform biopsies routinely and safely. There is additionally the issue of who will pay for the increased number of biopsies. While protocol biopsies may be useful in centers where there is sufficient expertise to perform them and ideally where concomitant immunologic studies can be performed, it is not clear that there is enough benefit to expand their use to every pediatric transplantation program. It would certainly be worth considering a large, multicenter randomized trial of protocol biopsies in pediatric kidney transplant recipients, along the lines of the Winnipeg trial, to see if there would be a demonstrated benefit, in terms of graft survival and function. This would be a worthwhile project for either the International Pediatric Transplantation Association (IPTA) or North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) to consider, and would provide a real answer to this question.

Vascular Access in Children: The Importance of Microsurgery for Creation of Autologous Arteriovenous Fistulae

Microsurgery gives much better immediate and long term results than classical surgery for the creation of direct arteriovenous fistulae, the best chronic access to blood in children.

Stature in children with chronic kidney disease: analysis of NAPRTCS database

Despite recent advances in the management of children with chronic kidney disease (CKD), growth remains suboptimal. The purpose of this study was to evaluate factors associated with short stature in children with CKD. We evaluated the chronic renal failure registry of the North American Pediatric Renal Transplant Cooperative Studies (NAPRTCS) to determine the relations among primary diagnosis, age, race, residual renal function, acidosis, anemia, serum phosphorous, calcium, parathyroid hormone (PTH), albumin, and height at entry into the registry in children with CKD. A total of 5,615 patients were entered into the registry between January 1994 and January 2004. We found that older patients, those with glomerular filtration rate (GFR) >50 ml min(-1) 1.73 m(-2), black patients and patients with focal segmental glomerulosclerosis (FSGS) were at lower risk of being short at entry. Anemia (hematocrit below 33%) was an independent risk factor for short stature. Acidosis, serum phosphorous, calcium, albumin and PTH at registration were poor predictors of short stature. Age, race, primary diagnosis, and residual renal function were associated with short stature in children with CKD.

Decreased Risk of Renal Allograft Thrombosis Associated With Interleukin-2 Receptor Antagonists: A Report of the NAPRTCS

Graft thrombosis is the most common cause of first year graft failure in pediatric renal transplantation. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database was analyzed for cases of graft failure due to thrombosis among patients transplanted from 1998 to 2004. The impact of interleukin-2 (IL-2) receptor antagonists as induction therapy was determined. There were a total of 51 graft failures due to thrombosis among the 2750 reported renal transplants (1.85%) (95% CI (1.39%, 2.41%)). This represents the most common cause of graft loss during the first year post-transplant accounting for 35% of first year losses and 18% of all graft losses. The incidence of thrombosis among patients who received IL-2 receptor antibodies was 1.07% (12/1126) compared to 2.40% (39/1624) among patients who did not (OR 0.44, 95% CI 0.23, 0.84, p = 0.014). Use of IL-2 receptor blockade was the only significant prognostic factor in a multivariate model with previously identified risk factors. Analysis of NAPRTCS data found that the use of IL-2 receptor antibodies as induction therapy is associated with a significantly decreased risk of graft failure due to thrombosis. This provocative finding requires further investigation to determine whether thrombotic failure can be decreased by this therapeutic strategy.