Medication adherence in pediatric renal transplant patients: The role of family functioning and parent health locus of control.

Children and adolescents with renal disease experience daily social, emotional, and medical challenges. Renal transplantation can help to improve quality of life but requires a lifelong regimen of immunosuppressant medication to maintain health. Adherence to a daily complex regimen can be difficult, particularly for adolescents who are beginning to develop autonomy from caregivers and are faced with a unique set of socio-emotional challenges. This study examines two factors that have shown to influence adherence in other pediatric populations, namely family functioning and parent health locus of control, from mothers' perspectives, in predicting medication non-adherence for adolescents (ages 12-19 years) 1 year post-transplant. Non-adherence was defined as the percentage of missed doses and late doses of the weekly immunosuppressant doses prescribed. Regression results demonstrated that mothers' perceptions of poorer overall family functioning predicted missed medication doses (ΔR2  = 0.383, F(7, 21) = 2.570, P = 0.044) with significant contributions in the domains of problem-solving (ß = -0.795, t(21) = -2.927, P = 0.008) and affective involvement (ß = 0.872, t(21) = 3.370, P = 0.003). Moreover, mothers who perceived that their adolescent had control over his/her health also predicted more missed medication doses (ΔR2  = 0.133, F(1, 27) = 5.155, P = 0.031). Important implications for these findings include implementation of family-based interventions that promote developmentally appropriate skills for adolescents and cultivate emotional involvement within the family.

Neonatal atypical hemolytic uremic syndrome from a factor H mutation treated with eculizumab.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) results from an inherited dysregulation of the alternative complement pathway leading to thrombotic microangiopathy consisting of hemolytic anemia, thrombocytopenia, and renal injury. The complement inhibitor eculizumab is an approved treatment, but its reported use in neonates - who have an inherently high risk of infection - is limited. CASE DIAGNOSIS/TREATMENT: A 28-day-old female presented with gross hematuria and hypertension. aHUS was suspected based on anemia with schistocytes, thrombocytopenia, low C3, and acute kidney injury requiring peritoneal dialysis. A septic work-up initiated on day 2 for hypothermia and respiratory failure was negative. There was no improvement after 6 days of plasma therapy. Despite being < 6 weeks old she was vaccinated with pneumococcal-13 conjugate, meningococcal (groups C and Y) polysaccharide, and Haemophilus b tetanus toxoid conjugate vaccines and started on penicillin prophylaxis. After 1 dose of eculizumab 300 mg, dialysis was discontinued and her hematological parameters improved. Genetic testing revealed a complement factor H mutation. After 11 months of follow-up, she remains on eculizumab and penicillin without recurrence of aHUS or any infectious complications. CONCLUSIONS: Eculizumab is a safe and effective treatment option for aHUS even in neonates at high risk for infection.

Streptococcal infection as possible trigger for dense deposit disease (C3 glomerulopathy).

UNLABELLED: Dense deposit disease (DDD, formerly known as membranoproliferative glomerulonephritis (MPGN) type II) is a subtype of C3 glomerulopathy (C3G). Electron-dense deposits in the glomerular basement membrane characterize this glomerulonephritis. DDD typically presents with a nephritic syndrome that progresses to end-stage renal failure in 50 % of patients despite treatment. The pathogenic basis of DDD is uncontrolled activation of the alternative complement cascade although the potential triggering events that precipitate the development of complement dysregulation are typically unknown. There are isolated reports of an apparent association between streptococcal infection and DDD, as well as with MPGN types I and III. However, this association has not been deemed compelling, perhaps because so few cases have been reported or because of a current lack of evidence for a plausible hypothesis to connect a streptococcal infection with subsequent disease. In this report, we describe two patients with DDD who definitely had an antecedent streptococcal infection with the phenotype of acute post-streptococcal glomerulonephritis and whose initial kidney biopsy findings on light microscopy were indistinguishable from acute post-streptococcal glomerulonephritis. These patients had additional points of interest: recurrence of gross hematuria with recurrent streptococcal infections, slowly progressive course, persistently low serum C3 concentration, positive C3 nephritic factor, and positive risk alleles in the complement factor H (CFH) gene. CONCLUSION: We suggest that streptococcal infection may trigger DDD in individuals genetically predisposed by virtue of a disorder in complement regulation.

Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach.

The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes a longitudinal observational cohort study, a pilot and ancillary study program, a training program, and a patient contact registry. NEPTUNE will enroll 450 adults and children with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy for detailed clinical, histopathological, and molecular phenotyping at the time of clinically indicated renal biopsy. Initial visits will include an extensive clinical history, physical examination, collection of urine, blood and renal tissue samples, and assessments of quality of life and patient-reported outcomes. Follow-up history, physical measures, urine and blood samples, and questionnaires will be obtained every 4 months in the first year and biannually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histological data for comprehensive analyses using systems biology approaches. Analytical strategies were designed to transform descriptive information to mechanistic disease classification for nephrotic syndrome and to identify clinical, histological, and genomic disease predictors. Thus, understanding the complexity of the disease pathogenesis will guide further investigation for targeted therapeutic strategies.

Endothelin antagonists in hypertension and kidney disease.

The endothelin (ET) system seems to play a pivotal role in hypertension and in proteinuric kidney disease, including the micro- and macro-vascular complications of diabetes. Endothelin-1 (ET-1) is a multifunctional peptide that primarily acts as a potent vasoconstrictor with direct effects on systemic vasculature and the kidney. ET-1 and ET receptors are expressed in the vascular smooth muscle cells, endothelial cells, fibroblasts and macrophages in systemic vasculature and arterioles of the kidney, and are associated with collagen accumulation, inflammation, extracellular matrix remodeling, and renal fibrosis. Experimental evidence and recent clinical studies suggest that endothelin receptor blockade, in particular selective ETAR blockade, holds promise in the treatment of hypertension, proteinuria, and diabetes. Concomitant blockade of the ETB receptor is not usually beneficial and may lead to vasoconstriction and salt and water retention. The side-effect profile of ET receptor antagonists and relatively poor antagonist selectivity for ETA receptor are limitations that need to be addressed. This review will discuss what is currently known about the endothelin system, the role of ET-1 in the pathogenesis of hypertension and kidney disease, and summarize literature on the therapeutic potential of endothelin system antagonism.

Mitochondrial tRNA(Phe) mutation as a cause of end-stage renal disease in childhood.

BACKGROUND: We identified a mitochondrial tRNA mutation (m.586 G > A) in a patient with renal failure and symptoms consistent with a mitochondrial cytopathy. This mutation was of unclear significance due to the absence of consistent reports of linkage to specific disease phenotypes and any data pertaining to its effects on mitochondrial function. CASE-DIAGNOSIS/TREATMENT: A 16-month-old girl with failure-to-thrive, developmental regression, persistent lactic acidosis, hypotonia, gastrointestinal dysmotility, adrenal insufficiency, and hematologic abnormalities developed hypertension and renal impairment with chronic tubulointerstitial fibrosis, progressing to renal failure with the need for peritoneal dialysis. Evaluation of her muscle and blood led to the identification of a mutation of the mitochondrial tRNA for phenylalanine, m.586 G > A. CONCLUSIONS: The m.586 G > A mutation is pathogenic and a cause of end-stage renal disease in childhood. The mutation interferes with the stability of tRNA(Phe) and affects the translation of mitochondrial proteins and the stability of the electron transport chain.

Living donor kidney donation: another form of white coat effect.

BACKGROUND/AIMS: Living donor nephrectomy can be associated with increases in blood pressure several years following the procedure, but the best method to assess blood pressure during the living donor evaluation process is unclear. METHODS: Living kidney donors underwent casual clinic and ambulatory blood pressure monitoring (ABPM) and measurement of central aortic pressures at baseline and 6 months following donor nephrectomy. RESULTS: There was a significant decline in clinic systolic blood pressure (SBP; p = 0.001) and central aortic systolic pressure (p = 0.011) during the study period. However, average ABPM was unchanged and other measures of central arterial pressures and Augmentation Index were unchanged at 6 months compared to baseline. CONCLUSIONS: The remarkable differences between clinic SBP and ambulatory SBP prior to donation, and the disappearance of these differences 6 months later, suggest a substantial white coat effect on SBP associated with living kidney donor evaluation. Also, ABPM represents a better way to assess blood pressure prior to kidney donation.

Outcomes in pediatric solid-organ transplantation.

LaR Pediatric solid-organ transplantation is an increasingly successful treatment for organ failure. Five- and 10-yr patient survival rates have dramatically improved over the last couple of decades, and currently, over 80% of pediatric patients survive into adolescence and young adulthood. Waiting list mortality has been a concern for liver, heart, and intestinal transplantation, illustrating the importance of transplant as a life-saving therapy. Unfortunately, the success of pediatric transplantation comes at the cost of long-term or late complications that arise as a result of allograft rejection or injury, immunosuppression-related morbidity, or both. As transplant recipients enter adolescence treatment, non-adherence becomes a significant issue, and the medical and psychosocial impacts transition to adulthood not only with regard to healthcare but also in terms of functional outcomes, economic potential, and overall QoL. This review addresses the clinical and psychosocial challenges encountered by pediatric transplant recipients in the current era. A better understanding of pediatric transplant outcomes and adult morbidity and mortality requires further ongoing assessment.

Association of Obesity with Cardiovascular Risk Factors and Kidney Disease Outcomes in Primary Proteinuric Glomerulopathies.

BACKGROUND/AIMS: Obesity is a known risk factor for cardiovascular disease and contributes to the development and progression of kidney disease. However, the specific influence of obesity on outcomes in primary glomerular disease has not been well characterized. METHODS: In this prospective cohort study, data were from 541 participants enrolled in the Nephrotic Syndrome Study Network (NEPTUNE), between 2010 and 2019, at 23 sites across North America. Blood pressure, lipids, and kidney disease outcomes including complete proteinuria remission, kidney failure, and chronic kidney disease progression were evaluated. Data were analyzed using linear and logistic regression with generalized estimating equations and time-varying Cox regression with Kaplan-Meier plots. RESULTS: The prevalence of obesity at baseline was 43.3% (N = 156) in adults and 37.6% (N = 68) in children. In adults, obesity was longitudinally associated with higher systolic BP (ß = 6.49, 95% CI: 2.41, 10.56, p = 0.002), dyslipidemia (OR = 1.74, 95% CI: 1.30, 2.32, p < 0.001), triglycerides (ß = 41.92, 95% CI: 17.12, 66.71, p = 0.001), and lower HDL (ß = -6.92, 95% CI: -9.32, -4.51, p < 0.001). In children, obesity over time was associated with higher systolic BP index (ß = 0.04, 95% CI: 0.02, 0.06, p < 0.001) and hypertension (OR = 1.43, 95% CI: 1.04, 1.98, p = 0.03). In both adults and children, obesity was associated with a significantly lower hazard of achieving complete remission of proteinuria (adult HR = 0.80, 95% CI: 0.69, 0.88, p < 0.001; pediatric HR = 0.72, 95% CI: 0.61, 0.84, p < 0.001). CONCLUSION: Obesity was associated with higher cardiovascular risk and less proteinuria remission from nephrotic syndrome in adults and children with proteinuric glomerulopathies. Weight-loss strategies may forestall cardiovascular disease and progressive kidney function decline in this high-risk patient group.

Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease.

Congenital Anomalies of the Kidney and Urinary Tract can be associated with Hirschsprung disease. We report on three children with a similar 16p11.2 microdeletion with a spectrum of clinical anomalies consisting of congenital anomalies of the kidney and urinary tract in two patients (Patients 1 and 2) and Hirschsprung disease in two patients (Patients 1 and 3), leading us to hypothesize that a gene in this region is associated with these phenotypes. Patient 1 presented with left renal agenesis, grade-IV vesicoureteral reflux, and Hirschsprung disease, Patient 2 with left renal agenesis, chronic kidney disease, chronic constipation, seizures, and developmental delay, and Patient 3 with Hirschsprung disease and normal kidneys. Genome-wide microarray analysis demonstrated overlapping microdeletions within 16p11.2. The shortest region of overlap in the three patients contained only eight genes, including the SH2 domain-containing binding protein 1 (SH2B1), an adaptor protein which has been implicated in enhancement of the tyrosine kinase activity of RET, whose role in developmental disease of the kidney and enteric enervation is well established. Our findings suggest that 16p11.2 deletions are associated with abnormalities of renal and enteric development and we hypothesize that deletion of SH2B1 may account for the observed phenotype.

Vascular involvement in tuberous sclerosis.

Vascular involvement in tuberous sclerosis (TS) is rare. Central and peripheral aneurysms and large and medium size arterial stenotic-occlusive disease have been reported in patients with TS. We present here three pediatric patients with TS and severe vascular abnormalities, followed by a review of the literature. The three cases include a 14-month-old girl with polycystic kidneys and cerebral tubers who had a large asymptomatic abdominal aortic aneurysm, a 2-year-old boy with multiple features of TS who had hypertension and was found to have mid-aortic syndrome with bilateral renal artery stenosis, and an 18-year-old girl with abdominal pain and TS features who had greater than 70% celiac artery stenosis. In all cases, noninvasive vascular imaging modalities were utilized for either initial diagnosis, surveillance, or both. These cases highlight the collaborative roles of the pediatric nephrologist and cardiovascular imager in the diagnosis and management of the vascular complications in TS patients. Appropriate care can only be made through a high index of suspicion.

USB drives for communication of medical information in a pediatric dialysis unit.

We evaluated the feasibility of using universal serial bus (USB) drives for communicating medical information between parents of children receiving dialysis and medical personnel during clinical encounters. When surveyed, parents and pediatric resident physicians supported the use of USB drives and were willing to use the devices. The utilization rate of USB drives was 57%.

Modeling of human anti-GBM antibody-alpha3(IV)NC1 interactions predicts antigenic cross-linking through contact of both heavy chains with repeating epitopes on alpha3(IV)NC1.

BACKGROUND/AIMS: Patients with anti-glomerular basement membrane diseases produce pathogenic autoantibodies (autoAb) that deposit in the kidney and initiate severe inflammation. Restricted antigenic specificity of the autoAb against 2 regions (with related sequences) within alpha3(IV)NC1, along with shared idiotypes (i.e. structural determinants), among pathogenic human autoAb suggested that common genetic elements encode the autoAb. The aim of this study was to determine whether the idiotypic relatedness of the autoAb was due to the fact that unique and similar genes were used to encode them, divergent genes were used to produce Ab with similar Ag-binding properties and conformation, or if other mechanisms were operative. METHODS: The encoding V gene sequences of pathogenic human anti-alpha3(IV)NC1 Ab, derived following immunization of XenoMice which produce human but not murine IgG, with alpha3(IV)NC1 were determined. Predicted conformations of autoAb-alpha3(IV)NC1 interactions were derived using the Ab sequences and molecularmodels of the alpha3(IV)NC1 structure. RESULTS: The pathogenic Ab were encoded by multiple, common V(H) and V(L) gene families indicating that they were not encoded by a unique subset of genes and that normal individuals have the capacity to produce them. However, modeling of the Ag-Ab interactions suggested that although the contact regions varied for individual Ab, the optimized energy constraints facilitate interaction of both Ab-binding regions with pathogenically relevant epitopes on alpha3(IV)NC1. CONCLUSIONS: The results suggest that the repetitive nature and relatedness of the alpha3(IV)NC1 antigenic epitopes facilitate cross-linking of pathogenic Ab, in vivo, by allowing both IgG Fab to bind to the basement membrane. This most likely accounts for the high-affinity Ab binding we and others observed among human anti-alpha3(IV)NC1 Ab. Based on these observations, we postulate that this interaction provides for the stability of the Ab interaction, resulting in a high-affinity interaction that serves as an ideal scaffold for optimal FcR engagement and complement activation, thereby accelerating inflammation and contributing to the rapidly progressive nature of this disease.

Perceived barriers to adherence among adolescent renal transplant candidates.

Non-adherence to medical regimens is a ubiquitous hindrance to quality health care among adolescent transplant recipients. Identification of potentially modifiable barriers to adherence when patients are listed for organ transplant would help with early intervention efforts to prepare adolescents for the stringent medication regimen post-transplant. Fifty-six adolescents listed for a kidney transplant, mean age 14.27 (s.d. = 2.2; range 11-18 yr), 73.2% male, 62.5% Caucasian participated in a semi-structured interview, the Medical Adherence Measure, to assesses the patient's knowledge of the prescribed regimen, reported adherence (missed and late doses), the system used to organized medications, and who holds the primary responsibility over medication management. Better knowledge of the medication regimen was associated with fewer missed doses (r = -0.48, p < 0.001). Patients who perceived more barriers had more missed (r = 0.38, p = 0.004) and late (r = 0.47, p < 0.001) doses. Patients who endorsed "just forget," the most common barrier (56.4%), reported significantly more missed (z = -4.25, p < 0.001) and late (z = -2.2, p = 0.02) doses. Only one-third of the transplant candidates used a pillbox to organize medications but these patients had significantly better adherence, z = -2.2, p = 0.03. With regard to responsibility over managing the regimens, adolescents missed fewer doses when their parents were in charge than when they were solely responsible, z = -2.1, p = 0.04. Interventions developed to prepare transplant candidates for a stringent post-transplant regimen need to focus on ensuring accurate knowledge of as simple a regimen as possible. Use of an organized system such as a pillbox to establish a routine and facilitate tracking of medications is recommended with integration of reminders that may be appealing for this age group. Although individuation is developmentally normative at this age, parent involvement seems critical until the adolescent is able to manage the responsibility more independently.

Successful deceased donor renal transplant in a sensitized pediatric recipient with the use of plasmapheresis.

Sensitization following renal transplant is a significant barrier to repeat transplantation in children. We report a successful DD renal transplant, with the use of PP, in an 11-yr-old girl who became highly sensitized following a prior failed transplant. She received PP treatments after failure of high-dose IVIg (Gamimune). We established the effectiveness of PP by attaining a 0% PRA and negative cross-matches after five PP treatments. Subsequently, our patient underwent a second round of scheduled PP. When the PRA was 0%, unacceptable antigens were removed from the UNOS wait list, PP was continued, and a kidney became available within 10 days. The final flow cytometry cross-match with the eventual donor was negative. This success demonstrates that coordination of desensitization by PP and advanced laboratory monitoring techniques with recent policies regarding allocation of organs to pediatric patients provides new opportunities for children awaiting transplantation. Since the transplant, our patient sustained a low-titer increase of anti-HLA antibodies. However, she has had no episodes of acute rejection and has maintained excellent graft function more than 17 months later.

Blood Pressure and Visit-to-Visit Blood Pressure Variability Among Individuals With Primary Proteinuric Glomerulopathies.

Hypertension and blood pressure variability (BPV; SD and average real variability) in primary proteinuric glomerulopathies are not well described. Data were from 433 participants in the NEPTUNE (Nephrotic Syndrome Study Network). Hypertensive BP status was defined as previous history of hypertension or BP ≥140/90 mm Hg for adults/≥95th percentile for children at baseline. BPV was measured in participants with ≥3 visits in the first year. Two-hundred ninety-six adults (43 years [interquartile range, 32-57.8 years], 61.5% male) and 147 children (11 years [interquartile range, 5-14 years], 57.8% male) were evaluated. At baseline, 64.8% of adults and 46.9% of children were hypertensive. Histological diagnosis was associated with hypertensive status in adults (P=0.036). In adults, hypertensive status was associated with lower hazard of complete remission (hazard ratio, 0.36; 95% confidence interval, 0.19-0.68) and greater hazard of achieving the composite end point (end-stage renal disease or estimated glomerular filtration rate decline >40%; hazard ratio, 4.1; 95% confidence interval, 1.4-12). Greater systolic and diastolic SD and average real variability were also associated with greater hazard of reaching the composite end point in adults (all P<0.01). In children, greater BPV was an independent predictor of composite end point (determined by systolic SD and average real variability) and complete remission (determined by systolic and diastolic average real variability; all P<0.05). Hypertensive status was common among adults and children enrolled in NEPTUNE. Differences in hypertensive status prevalence, BPV, and treatment were found by age and histological diagnosis. In addition, hypertensive status and greater BPV were associated with poorer clinical outcomes.

Vascular Stiffness in Children With Chronic Kidney Disease.

Carotid-femoral pulse wave velocity (cfPWV) is a measure of arterial stiffness associated with cardiovascular events in the general population and in adults with chronic kidney disease. However, few data exist regarding cfPWV in children with chronic kidney disease. We compared observed cfPWV assessed via applanation tonometry in children enrolled in the CKiD cohort study (Chronic Kidney Disease in Children) to normative data in healthy children and examined risk factors associated with elevated cfPWV. cfPWV Z score for height/gender and age/gender was calculated from and compared with published pediatric norms. Multivariable linear regression was used to assess the relationship between cfPWV and age, gender, race, body mass index, diagnosis, urine protein-creatinine ratio, mean arterial pressure, heart rate, number of antihypertensive medications, uric acid, and serum low-density lipoprotein. Of the 95 participants with measured cfPWV, 60% were male, 19% were black, 46% had glomerular cause of chronic kidney disease, 22% had urine protein-creatinine ratio 0.5 to 2.0 mg/mg and 9% had >2.0 mg/mg, mean age was 15.1 years, average mean arterial pressure was 80 mm Hg, and median glomerular filtration rate was 63 mL/min per 1.73 m2 Mean cfPWV was 5.0 m/s (SD, 0.8 m/s); mean cfPWV Z score by height/gender norms was -0.1 (SD, 1.1). cfPWV increased significantly with age, mean arterial pressure, and black race in multivariable analysis; no other variables, including glomerular filtration rate, were independently associated with cfPWV. In this pediatric cohort with mild kidney dysfunction, arterial stiffness was comparable to that of normal children. Future research is needed to examine the impact of chronic kidney disease progression on arterial stiffness and associated cardiovascular parameters in children.

Complete Remission in the Nephrotic Syndrome Study Network.

BACKGROUND AND OBJECTIVES: This analysis from the Nephrotic Syndrome Study Network (NEPTUNE) assessed the phenotypic and pathology characteristics of proteinuric patients undergoing kidney biopsy and defined the frequency and factors associated with complete proteinuria remission (CRever). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We enrolled adults and children with proteinuria ≥0.5 g/d at the time of first clinically indicated renal biopsy at 21 sites in North America from April 2010 to June 2014 into a prospective cohort study. NEPTUNE central pathologists assigned participants to minimal-change disease (MCD), FSGS, membranous nephropathy, or other glomerulopathy cohorts. Outcome measures for this analysis were (1) CRever with urine protein-to-creatinine ratio (UPC) <0.3 g/g with preserved native kidney function and (2) ESRD. Continuous variables are reported as median and interquartile range (IQR; 25th, 75th percentile). Cox proportional hazards modeling was used to assess factors associated with CRever. RESULTS: We enrolled 441 patients: 116 (27%) had MCD, 142 (32%) had FSGS, 66 (15%) had membranous nephropathy, and 117 (27%) had other glomerulopathy. The baseline UPC was 4.1 g/g (IQR, 1.9, 7.7) and the eGFR was 81 ml/min per 1.73 m(2) (IQR, 50, 105). Median duration of observation was 19 months (IQR, 11, 30). CRever occurred in 46% of patients, and 4.6% progressed to ESRD. Multivariate analysis demonstrated that higher prebiopsy proteinuria (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.5) and pathology diagnosis (FSGS versus MCD; hazard ratio, 0.2; 95% confidence interval, 0.1 to 0.5) were inversely associated with CRever. The effect of immunosuppressive therapy on remission varied by pathology diagnosis. CONCLUSIONS: In NEPTUNE, the high frequency of other pathology in proteinuric patients affirms the value of the diagnostic kidney biopsy. Clinical factors, including level of proteinuria before biopsy, pathology diagnosis, and immunosuppression, are associated with complete remission.

Chromophobe renal cell carcinoma in a pediatric living-related kidney transplant recipient.

Renal cell carcinoma can occur in children who have received renal allografts from adults. Chromophobe renal cell carcinoma is a rare variant of renal carcinoma with distinct histochemical, ultrastructural, and genetic characteristics. We describe the incidental finding of a chromophobe renal cell carcinoma in a 13 1/2-year-old boy 5 years after receiving a living-related renal transplant. This tumor was found by serendipity during the evaluation of fever and inguinal lymphadenopathy, with the presumptive diagnosis of posttransplantation lymphoproliferative disorder. The patient was found to have cat-scratch disease. A renal cell carcinoma should be considered in the differential diagnosis of a pediatric recipient of an adult kidney with an incidental finding of a tumor in the graft.

Evaluation of hematuria in children.

The detection of blood in a child's urine is alarming and often prompts many laboratory studies. Hematuria is one of the most important signs of renal or bladder disease, but proteinuria often is a more important diagnostic and prognostic finding. The physician should ensure that serious conditions are not overlooked, avoid unnecessary laboratory studies, reassure the family, and provide guidelines for additional studies if there is a change in the child's course. This article provides an approach to the evaluation and management of hematuria in a child. Many tests have been recommended for the child with hematuria, but no consensus exists on a systematic evaluation.