Two infants with bilateral renal agenesis who were bridged by chronic peritoneal dialysis to kidney transplantation.

Bilateral renal agenesis is associated with severe oligohydramnios and was considered incompatible with postnatal life due to severe pulmonary hypoplasia. The use of renal replacement therapy was limited by significant morbidity and mortality associated with dialysis in very young infants with major pulmonary pathology. In the United States, there is a tremendous controversy about whether or not the use of prenatal amniotic fluid infusions provides a benefit to fetuses with bilateral renal agenesis. One of the critical issues identified is that there are, as yet, no children reported who had achieved long-term survival. Previous reports all indicated these children died shortly after birth or after unsuccessful peritoneal dialysis. We present two infants with a prenatal diagnosis of bilateral renal agenesis whose mothers elected to undergo prenatal amnioinfusions. One was born at 28 weeks with a birthweight of 1230 g and the other born at 34 weeks with a birthweight of 1940 g. We present the details of both cases, with initial management on chronic peritoneal dialysis, which started shortly after birth, as a bridge to living related kidney transplants.

The prospective pediatric continuous renal replacement therapy (ppCRRT) registry: a critical appraisal.

Continuous renal replacement therapy (CRRT), which provides gradual, predictable clearance and fluid removal, is commonly used to manage acute kidney injury (AKI) and fluid overload in critically ill children. The Prospective Pediatric CRRT (ppCRRT) Registry, founded in 2001 and comprising 13 pediatric centers in the United States, represents the largest cohort of children receiving CRRT to date. Data from the ppCRRT has been used to describe pediatric CRRT demographics and epidemiology, improve technical aspects of CRRT provision for children, and identify novel or underappreciated risk factors affecting survival. Whereas the registry has successfully answered many questions, a number of questions remain unanswered and new ones have arisen. This article describes the ppCRRT Registry, including its major findings, the lessons learned, and the limitations inherent in its design. Additionally, using the registry as a framework, areas of future study are identified and potential methodologies examined.

Association between maintenance fluid tonicity and hospital-acquired hyponatremia.

OBJECTIVE: To evaluate whether the administration of hypotonic fluids compared with isotonic fluids is associated with a greater risk for hyponatremia in hospitalized children. STUDY DESIGN: Informatics-enabled cohort study of all hospitalizations at Lucile Packard Children's Hospital between April 2009 and March 2011. Extraction and analysis of electronic medical record data identified normonatremic hospitalized children who received either hypotonic or isotonic intravenous maintenance fluids upon admission. The primary exposure was the administration of hypotonic maintenance fluids, and the primary outcome was the development of hyponatremia (serum sodium <135 mEq/L). RESULTS: A total of 1048 normonatremic children received either hypotonic (n = 674) or isotonic (n = 374) maintenance fluids upon admission. Hyponatremia developed in 260 (38.6%) children who received hypotonic fluids and 104 (27.8%) of those who received isotonic fluids (unadjusted OR 1.63; 95% CI 1.24-2.15, P < .001). After we controlled for intergroup differences and potential confounders, patients receiving hypotonic fluids remained more likely to develop hyponatremia (aOR 1.37, 95% CI 1.03-1.84). Multivariable analysis identified additional factors associated with the development of hyponatremia, including surgical admission (aOR 1.44, 95% CI 1.09-1.91), cardiac admitting diagnosis (aOR 2.08, 95% CI 1.34-3.20), and hematology/oncology admitting diagnosis (aOR 2.37, 95% CI 1.74-3.25). CONCLUSIONS: Hyponatremia was common regardless of maintenance fluid tonicity; however, the administration of hypotonic maintenance fluids compared with isotonic fluids was associated with a greater risk of developing hospital-acquired hyponatremia. Additional clinical characteristics modified the hyponatremic effect of hypotonic fluid, and it is possible that optimal maintenance fluid therapy now requires a more individualized approach.

End-stage renal disease due to lupus nephritis among children in the US, 1995-2006.

OBJECTIVE: To identify predictors of wait-listing for kidney transplantation, kidney transplantation, and mortality among children with lupus nephritis-associated end-stage renal disease (ESRD). METHODS: Children ages 5-18 years with new-onset lupus nephritis-associated ESRD were identified in the US Renal Data System (1995-2006). Demographic and clinical characteristics, causes of death, and predictors of wait-listing for kidney transplantation, kidney transplantation, and mortality during the first 5 years of ESRD were investigated. Cox proportional hazards models were used. RESULTS: A total of 583 children had incident lupus nephritis-associated ESRD. The mean ± SD age of the patients at the time of ESRD onset was 16.2 ± 2.4 years; 49% were African American, and 24% were Hispanic. During the 5-year period after the onset of ESRD, 292 (49%) were wait-listed, 193 (33%) received a kidney transplant, and 131 (22%) died. The main causes of death were cardiopulmonary (31%) and infectious (16%). Children living in the northeast and west were more than twice as likely as children in the south to be wait-listed and were >50% more likely than children in the south to undergo transplantation. There were fewer kidney transplants among older versus younger patients (odds ratio [OR] 0.59, P = 0.009), African American versus white patients (OR 0.48, P < 0.001), Hispanic versus non-Hispanic patients (OR 0.63, P = 0.03), and those with Medicaid versus those with private insurance (OR 0.70, P = 0.03). Mortality among African American children was almost double that among white children (OR 1.83, P < 0.001). CONCLUSION: Among US children with lupus nephritis-associated ESRD, age, race, ethnicity, type of medical insurance, and geographic region were associated with significant variation in 5-year wait-listing for kidney transplantation, kidney transplantation, and mortality.

Complement-fixing donor-specific antibodies identified by a novel C1q assay are associated with allograft loss.

Long-term outcomes following renal transplantation remain disappointing. Recently, interest has focused on the antibody-mediated component of allograft injury and the deleterious effects of DSA. We applied a novel C1q solid-phase assay in parallel with the standard IgG SAB assay to identify DSA with the potential to activate complement by binding C1q. Among 193 consecutive renal transplants at our center, 19.2% developed de novo DSA following transplantation. Of the patients with DSA, 43% had antibodies that bound C1q in vitro [C1q+ DSA]. Patients with C1q+ DSA were more likely to develop allograft loss than patients with DSA that did not bind C1q (46.7% vs. 15%; p = 0.04); patients with C1q+ DSA were nearly six times more likely to lose their transplant than those with C1q- DSA. Additionally, patients with C1q+ DSA who underwent allograft biopsy were more likely to demonstrate C4d deposition (50% vs. 8%; p = 0.03) and meet criteria for acute rejection (60% vs. 17%; p = 0.02) when compared with patients with DSA that did not bind C1q. These data suggest that DSA with the ability to activate complement, as determined by this novel C1q assay, are associated with greater risk of acute rejection and allograft loss.

Continuous renal replacement therapy in children.

Over the past several decades, the epidemiology of acute kidney injury (AKI) in children has changed significantly. Pediatric patients with AKI frequently have co-morbid conditions, substantial fluid overload, and marked disease severity. At the same time, continuous renal replacement therapy (CRRT) has become the preferred modality for the management of these patients. This manuscript provides a state-of-the-art review of the technical aspects of pediatric CRRT and examines the most recent data regarding CRRT indications, timing of initiation, dosing, and outcomes in critically ill children.

Nonrenal indications for continuous renal replacement therapy: A report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

OBJECTIVE: Continuous renal replacement therapy is the most often implemented dialysis modality in the pediatric intensive care unit setting for patients with acute kidney injury. However, it also has a role in the management of patients with nonrenal indications such as clearance of drugs and intermediates of disordered cellular metabolism. MEASUREMENTS AND METHODS: Using data from the multicenter Prospective Pediatric Continuous Renal Replacement Therapy Registry, we report a cohort of pediatric patients receiving continuous renal replacement therapy for nonrenal indications. Nonrenal indications were obtained from the combination of "other" category for continuous renal replacement therapy initiation and patient diagnosis (both primary and secondary). This cohort was further divided into three subgroups: inborn errors of metabolism, drug toxicity, and tumor lysis syndrome. RESULTS: From 2000 to 2005, a total of 50 continuous renal replacement therapy events with nonrenal indications for therapy were included in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. Indication-specific survival of the subgroups was 62% (inborn errors of metabolism), 82% (tumor lysis syndrome), and 95% (drug toxicity). The median small solute dose delivered among the subgroups ranged from 2125 to 8213 mL/1.73 m/hr, with 54%-59% receiving solely diffusion-based clearance as continuous venovenous hemodialysis. No association was established between survival and dose delivered, modality of continuous renal replacement therapy, or use of intermittent hemodialysis prior to continuous renal replacement therapy. CONCLUSIONS: Pediatric patients requiring continuous renal replacement therapy for nonrenal indications are a distinct cohort within the population receiving renal replacement therapy with little published experience of outcomes for this group. Survival within this cohort varies by indication for continuous renal replacement therapy and is not associated with continuous renal replacement therapy modality. Additionally, survival is not associated with small solute doses delivered within a cohort receiving >2000 mL/1.73 m/hr. Our data suggest metabolic control is established rapidly in pediatric patients and that acute detoxification may be provided with continuous renal replacement therapy for both the initial and maintenance phases of treatment using either convection or diffusion at appropriate doses.

Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry.

BACKGROUND: Critically ill children with hemodynamic instability and acute kidney injury often develop fluid overload. Continuous renal replacement therapy (CRRT) has emerged as a favored modality in the management of such children. This study investigated the association between fluid overload and mortality in children receiving CRRT. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry. PREDICTOR: Fluid overload from intensive care unit (ICU) admission to CRRT initiation, defined as a percentage equal to (fluid in [L] - fluid out [L])/(ICU admit weight [kg]) x 100%. OUTCOME & MEASUREMENTS: The primary outcome was survival to pediatric ICU discharge. Data were collected regarding demographics, CRRT parameters, underlying disease process, and severity of illness. RESULTS: 153 patients (51.5%) developed < 10% fluid overload, 51 patients (17.2%) developed 10%-20% fluid overload, and 93 patients (31.3%) developed > or = 20% fluid overload. Patients who developed > or = 20% fluid overload at CRRT initiation had significantly higher mortality (61/93; 65.6%) than those who had 10%-20% fluid overload (22/51; 43.1%) and those with < 10% fluid overload (45/153; 29.4%). The association between degree of fluid overload and mortality remained after adjusting for intergroup differences and severity of illness. The adjusted mortality OR was 1.03 (95% CI, 1.01-1.05), suggesting a 3% increase in mortality for each 1% increase in severity of fluid overload. When fluid overload was dichotomized to > or = 20% and < 20%, patients with > or = 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, 2.8-25.7). LIMITATIONS: This was an observational study; interventions were not standardized. The relationship between fluid overload and mortality remains an association without definitive evidence of causality. CONCLUSIONS: Critically ill children who develop greater fluid overload before initiation of CRRT experience higher mortality than those with less fluid overload. Further goal-directed research is required to accurately define optimal fluid overload thresholds for initiation of CRRT.

Enterococcal peritonitis in children receiving chronic peritoneal dialysis.

BACKGROUND: Peritonitis is a common complication of chronic peritoneal dialysis (CPD) and can be associated with technique failure. Enterococcus is an uncommon peritoneal pathogen in children receiving CPD but represents a potential therapeutic challenge due to its innate resistance to cephalosporins and emerging resistance to glycopeptides. METHODS: The International Pediatric Peritonitis Registry is a global consortium of 47 paediatric dialysis centres designed to address validation of the International Society for Peritoneal Dialysis paediatric peritonitis treatment guidelines. Between 2001 and 2004, peritonitis episodes were assessed in 392 participating children receiving CPD. RESULTS: Among the 392 patients, 340 episodes of culture-positive peritonitis were evaluated. Twenty of these episodes were due to Enterococcus species (5.9%). There were no clinical characteristics uniquely associated with enterococcal peritonitis at presentation. After 3 days of therapy, 75% of patients were pain free, 95% had decreased effluent cloudiness and 90% were afebrile. Only one patient required a catheter exchange, and all patients experienced full functional recovery. Despite broad in vitro resistance to cephalosporins and 21% resistance to glycopeptides, neither in vitro resistance pattern nor choice of empiric antibiotic regimen affected short- or long-term outcomes. CONCLUSIONS: Enterococci are likely responsible for ∼6% of culture-positive peritonitis episodes in children receiving CPD. Although it was not possible to identify patients with enterococcal peritonitis based on presentation, clinical response was not associated with in vitro resistance patterns, and patients who initially received a cephalosporin-based empiric regimen until culture results are available are likely to respond quickly and have full functional recovery.

Protein and calorie prescription for children and young adults receiving continuous renal replacement therapy: a report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

OBJECTIVE: Few published reports describe nutrition provision for critically ill children and young adults with acute kidney injury receiving continuous renal replacement therapy. The goals of this study were to describe feeding practices in pediatric continuous renal replacement therapy and to evaluate factors associated with over- and under-prescription of protein and calories. DESIGN: Retrospective database study. SETTING: Multicenter study in pediatric critical care units. PATIENTS: Patients with acute kidney injury (estimated glomerular filtration rate < 75 mL/min/1.73 m at continuous renal replacement therapy initiation) enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. INTERVENTIONS: None. MEASUREMENTS: Nutrition variables: initial and maximal protein (g/kg/day) and caloric (kcal/kg/day) prescription and predicted resting energy expenditure (kcal/kg/day). We determined factors predicting initial and maximal protein and caloric prescription by multivariate analysis. RESULTS: One hundred ninety-five patients (median [interquartile range] age = 8.1 [12.8] yrs, 56.9% men) were studied. Mean protein and caloric prescriptions at continuous renal replacement therapy initiation were 1.3 +/- 1.5 g/kg/day (median, 1.0; range, 0-10) and 37 +/- 27 kcal/kg/day (median, 32; range, 0-107). Mean maximal protein and caloric prescriptions during continuous renal replacement therapy were 2.0 +/- 1.5 g/kg/day (median, 1.7; range, 0-12) and 48 +/- 32 kcal/kg/day (median, 43; range, 0-117). Thirty-four percent of patients were initially prescribed < 1 g/kg/day protein; 23% never attained > 1 g/kg/day protein prescription. By continuous renal replacement therapy day 5, median protein prescribed was > 2 g/kg/day. Protein prescription practices differed substantially between medical centers with 5 of 10 centers achieving maximal protein prescription of > 2 g/kg/day in > or = 40% of patients. Caloric prescription exceeded predicted resting energy expenditure by 30%-100%. Factors independently associated with maximal protein and caloric prescription while on continuous renal replacement therapy were younger age, initial protein and caloric prescription and number of continuous renal replacement therapy treatment days (p < 0.05). CONCLUSIONS: Protein prescription in pediatric continuous renal replacement therapy may be inadequate. Inter-center variation exists with respect to nutrition prescription. Feeding practice standardization and research in pediatric acute kidney injury nutrition are essential to begin providing evidence-based feeding recommendations.

Acute kidney injury in pediatric stem cell transplant recipients.

Because respiratory dysfunction after hematopoietic stem cell transplantation is a manifestation of a continuum of dysfunction temporarily induced by the transplant process, a proactive rather than reactive approach might prevent or attenuate its progression to acute respiratory distress syndrome. Organ dysfunction in this population results from cytokine-driven processes, of which the first manifestation includes fluid accumulation. We describe a multistep protocol that first targets fluid balance control, both through restriction of intake and through augmentation of output using dopamine and furosemide infusions. If these steps fail to stem the tide of water accumulation, we advocate the relatively early use of continuous renal replacement therapy, its use triggered by a continued increase in body weight (>10% above baseline), an increasing c-reactive protein level, and an increasing oxygen need. Renal function parameters do not figure in this protocol. We recommend continuous renal replacement therapy at 35 mL/kg/h (2,000 mL/1.73 m(2)/h), a dose that allows adequate flexibility in fluid management and that may provide effective clearance of proinflammatory (and anti-inflammatory) mediators that drive the evolving dysfunction. Proactive intervention improves the clinical status such that the transition to mechanical ventilation may proceed smoothly or in some cases even may be avoided altogether.

Safety and pharmacokinetics of daclizumab in pediatric renal transplant recipients.

This study examined the safety and pharmacokinetics/pharmacodynamics of daclizumab in combination with mycophenolate mofetil (or azathioprine), corticosteroids, and cyclosporine or tacrolimus, in 61 pediatric renal allograft recipients in three age groups: less than or equal to five yr (n = 18), 6-12 yr (n = 18), and 13-17 yr (n = 25). The dosing regimen was daclizumab 1.0 mg/kg before transplantation, followed by four biweekly doses. The pharmacokinetics of daclizumab were described using NONMEM software. Median (range) estimated trough daclizumab levels achieved on day 56 (before dose 5) were 3.88 microg/mL (2.48-8.78), 4.54 microg/mL (1.79-18.7), and 4.94 microg/mL (0.05-10.6) in the less than or equal to five yr (n = 15), 6-12 yr (n = 17), and 13-17 yr (n = 22) age groups, respectively. Steady-state median (range) daclizumab exposures were 2040 mg x h/mL (1585-3778), 2757 mg x h/mL (1873-3494) and 3297 mg x h/mL (1705-6453), respectively. Saturation of the IL-2R occurred rapidly and was maintained for greater than or equal to three months after transplantation. Daclizumab was generally well-tolerated with no acute allergic or anaphylactic reactions, deaths or malignancies during the study. The proportion of patients who developed acute rejection at six and 12 months was 8.5% and 16.7%, respectively. This study shows that adding daclizumab at 1 mg/kg to standard immunosuppressive therapy provides safe and effective IL-2R blockade.

Combined liver-kidney transplantation in children: indications and outcome.

Although it remains a relatively infrequent procedure in children, CLKT has become a viable option for a select group of pediatric patients with severe liver and kidney disease. Most are performed for rare primary diseases such as PH1, but a selected few are performed in the setting of concomitant hepatic and renal failure of uncertain etiology and prognosis. This article reviews the indications for and outcomes following CLKT in children. While it focuses on the specific primary diseases which impact liver and kidney function simultaneously, it addresses the indications based on concomitant hepatic and renal failure, such as seen in the hepatorenal syndrome, as well.

Clinical review: alternative vascular access techniques for continuous hemofiltration.

Obtaining or maintaining vascular access for continuous hemofiltration can sometimes be problematic, especially in the child or adult in multiple organ failure with edema and/or coagulopathy. Problems commonly encountered include obstruction of the femoral vein by the catheter, insertion difficulties, safety concerns when cannulating the subclavian vein in coagulopathy, and catheter and circuit occlusion due to disseminated intravascular coagulation. For access in infants we describe a technique utilizing two single-lumen thin-walled vascular sheaths. For infants and small children initial access to the vein may be difficult due to edema or poor perfusion. For this situation we describe the 'mini-introducer' technique of securing the vein and facilitating subsequent insertion of a relatively large guide wire. At any age an alternative route to the subclavian vein, from above the clavicle, is potentially 'compressible' in the event of hemorrhage during the procedure. We remind the reader of the utility of ultrasound guidance for cannulation of the internal jugular and subclavian veins. And lastly we review the options for venous return via the umbilical vein in infants, and via the antecubital vein in larger children and adults.

The international pediatric peritonitis registry: a global Internet-based initiative in pediatric dialysis.

OBJECTIVES: Recommendations for the management of peritoneal dialysis-associated peritonitis in children have recently been developed by an International Society for Peritoneal Dialysis (ISPD) expert committee. The International Pediatric Peritonitis Registry (IPPR) was established in October 2001 as a global consortium of 47 pediatric dialysis centers in order to assess the validity of these guidelines. DESIGN: The IPPR is an internet-based registry collecting data on pediatric peritonitis episodes treated according to the ISPD guidelines. Data on 375 episodes have been collected as of July 2004. DATA ACQUISITION: Detailed data are obtained online on the diagnosis of peritonitis, antibiotic and adjunctive therapy, as well as on possible risk factors and treatment results. CONCLUSIONS: Final data analysis of the IPPR will yield extensive information on the treatment and outcome of peritoneal dialysis-associated peritonitis in children.

Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation.

BACKGROUND: Corticosteroids have been invariant transplant immunosuppressives with numerous adverse effects. We previously reported 6-month results in 10 patients using extended daclizumab induction to safely eliminate steroid use in pediatric renal transplantation. This expanded pilot series discusses immunosuppression dosing modification to further minimize drug toxicity without sacrificing regimen efficacy. METHODS: Fifty-seven pediatric renal transplant recipients were enrolled in the pilot steroid-free protocol. Extended daclizumab induction, tacrolimus, and mycophenolate mofetil (MMF) were intended maintenance drugs. Fourteen patients were equal to or younger than 5 years, and 43 patients were older than 5 years of age at transplantation. There were seven protocol breaks. Study patients underwent serial protocol transplant biopsies (n=246), and serum daclizumab and mycophenolic acid (MPA) trough levels were evaluated. In this efficacy study, controls were 50 historical-matched steroid-based children receiving tacrolimus with 100% 2-year graft survival and without delayed graft function. RESULTS: Mean follow-up was 20 (range, 4.5-41) months with 98% overall graft and patient survival. At 1 year of analysis, steroid-free recipients showed significant improvements for clinical acute rejection (8%), graft function, hypertension, and growth, without increased infectious complications. Leukopenia, anemia, and allograft nephrotoxicity were addressed by solely decreasing MMF and tacrolimus dosing and/or by replacing MMF with sirolimus, without increasing acute rejection. Early daclizumab levels of more than 5 microg/mL were observed for the first time in children of all ages. CONCLUSIONS: Pediatric renal transplantation is safe without steroids. Daclizumab first-dose doubling and extended use for 6 months replaces steroids effectively without evidence of overimmunosuppression and may be the pivotal cause for the reduced acute rejection seen in this trial. This pilot study provides preliminary data to test this protocol in a prospective, multicenter randomized study.

Identification of Epstein-Barr virus-specific CD8+ T lymphocytes in the circulation of pediatric transplant recipients.

BACKGROUND: Pediatric transplant recipients are at increased risk for Epstein Barr virus (EBV)-related B cell lymphomas. In healthy individuals, the expansion of EBV-infected B cells is controlled by CD8+ cytotoxic T cells. However, immunosuppressive therapy may compromise antiviral immunity. We identified and determined the frequency of EBV-specific T cells in the peripheral blood of pediatric transplant recipients. METHODS: HLA-B*0801 and HLA-A*0201 tetramers folded with immunodominant EBV peptides were used to detect EBV-specific CD8+ T cells by flow cytometry in peripheral blood mononuclear cells from 24 pediatric liver and kidney transplant recipients. The expression of CD38 and CD45RO on EBV-specific, tetramer-binding cells was also examined in a subset of patients by immunofluorescent staining and flow cytometry. RESULTS: Tetramer-binding CD8+ T cells were identified in 21 of 24 transplant recipients. EBV-specific CD8+ T cells were detected as early as 4 weeks after transplant in EBV seronegative patients receiving an organ from an EBV seropositive donor. The frequencies (expressed as a percentage of the CD8+ T cells) of the tetramer-binding cells were HLA-B8-RAKFKQLL (BZLF1 lytic antigen peptide) tetramer, range=0.96 to 3.94%; HLA-B8-FLRGRAYGL (EBNA3A latent antigen peptide) tetramer, range=0.03 to 0.59%; and HLA-A2-GLCTLVAML (BMLF1 lytic antigen peptide) tetramer, range=0.06 to 0.76%. The majority of tetramer reactive cells displayed an activated/memory phenotype. CONCLUSIONS: Pediatric transplant recipients receiving immunosuppression can generate EBV-specific CD8+ T cells. Phenotypic and functional analysis of tetramer cells may prove useful in defining and monitoring EBV infection in the posttransplant patient.

Unexpectedly high prevalence of posttransplant anemia in pediatric and young adult renal transplant recipients.

BACKGROUND: Although posttransplant anemia (PTA) is recognized as a common problem in adult renal transplant recipients, few pediatric studies have been published. METHODS: In this retrospective cohort study of 162 pediatric renal transplant recipients treated at Stanford University, the authors sought to determine the prevalence, severity, and the predictive factors of PTA. Anemia was defined as a hematocrit (HCT) level greater than 2 SD below published means for age or as erythropoietin dependency to maintain a normal HCT. RESULTS: Sixty-seven percent of pediatric renal transplant recipients were anemic at the time of transplantation. The prevalence of anemia increased to 84.3% in the first month posttransplant. From 6 months to 60 months posttransplant, the prevalence of anemia remained high at 64.2% to 82.2%. Only 4 patients (2.5%) were never anemic. Iron depletion was detected in 19 of 26 and 23 of 23 anemic patients 12 and 60 months posttransplant, respectively. Serum erythropoietin levels were low relative to hematocrit levels in 38 of 56 anemic patients. Logistic regression at 3 months posttransplant showed that discharge hematocrit level (P < 0.0001), calcium (P = 0.0004), and cyclosporine dose (P = 0.0002) correlated with anemia. Creatinine clearance (P = 0.002) and white blood cell count (P = 0.004) correlated with anemia at 12 months posttransplant, but only creatinine clearance (P = 0.011) correlated with anemia 60 months posttransplant. CONCLUSION: Nearly all pediatric renal transplant recipients experience PTA. However, few children less than 2 years of age were anemic during the first year posttransplant. Antirejection therapy, bone disease, iron depletion, and creatinine clearance appear to play pivotal roles in the development of PTA in children.

Response to recombinant hepatitis B vaccine in children and adolescents with chronic renal failure.

BACKGROUND: Diminished antibody responses to the dosage of hepatitis B (HB) vaccine indicated for healthy adults has led to a greater dosage recommendation (40 microg of HB surface antigen [HBsAg]) for adults with chronic renal failure (CRF), but an appropriate dosage for children with CRF has not been established. METHODS: Seventy-eight children and adolescents with CRF (22 patients, predialysis; 42 patients, chronic dialysis therapy; 14 renal transplant recipients) aged 1 to 19 years (mean, 10.1 years) were enrolled onto a study to test a three 20-microg dose course of the HB vaccine Recombivax HB (Merck & Co, Inc, West Point, PA). RESULTS: The vaccine was well tolerated; no patient had a serious adverse event attributable to vaccine, and no patient withdrew from the study because of an adverse event. Overall, 91% of 66 patients administered three doses had a protective titer of 10 mIU/mL or greater for antibody against HBsAg (anti-HBs) and a geometric mean titer (GMT) of 733 mIU/mL, with seroprotection rates and GMTs among predialysis, dialysis, and renal transplant patients of 100% (4,140 mIU/mL), 94% (419 mIU/mL), and 64% (152 mIU/mL), respectively. All (100%) predialysis patients had a 10-mIU/mL or greater anti-HBs titer after only two doses of vaccine compared with 64% of dialysis patients and 50% of transplant recipients. Eighty-eight percent of 57 fully vaccinated patients tested 12 months after the first dose retained a 10-mIU/mL or greater anti-HBs titer. CONCLUSION: A regimen of three 20-microg doses of Recombivax HB is suitably immunogenic for children with CRF not administered immunosuppressive medication. When possible, at least two, and preferably all three, doses of vaccine should be administered before progression to end-stage renal disease.