Background. The epidemiology and morbidity of Epstein-Barr virus (EBV) infection in pediatric renal transplant recipients have been characterized insufficiently. Methods. In a prospective, ...multicenter study among 106 pediatric kidney allograft recipients aged 11.4 ± 5.9 years, we investigated the epidemiology of EBV infection and the relationship between EBV load, EBV serology, and EBV-related morbidity (posttransplant lymphoproliferative disease PTLD or symptomatic EBV infection, defined as flu-like symptoms or infectious mononucleosis). Results. EBV primary infection occurred in 27 of 43 (63%) seronegative patients and reactivation/reinfection in 28 of 63 (44%) seropositive patients. There was no association between the degree or duration of EBV load and EBV-related morbidity: The vast majority (17 of 18 94%) of patients with a high, persistent EBV load remained PTLD-free throughout a follow-up of 5.0 ± 1.3 years, while 2 of 3 (66%) patients with EBV-related PTLD exhibited only a low EBV load beforehand. Eight of 18 (44%) patients with a high, persistent EBV load remained asymptomatic during a follow-up of 5.3 ± 2.9 years. Multivariate analysis identified the EBV high-risk (D + /R − ) serostatus (odds ratio OR, 7.07; P < .05), the presence of human leukocyte antigen (HLA)–DR7 (OR, 5.65; P < .05), and the intensity of the immunosuppressive therapy (OR, 1.53; P < .01) as independent risk factors for the development of a symptomatic EBV infection. Conclusions. Presence of EBV high-risk seroconstellation, HLA-DR7, and intensity of immunosuppressive therapy are significant risk factors for a symptomatic EBV infection, whereas there is no close association between the degree or duration of EBV load and EBV-related morbidity. Clinical Trials Registration. NCT00963248.
DEAP-HUS
De
ficiency of CFHR (complement factor H-related) plasma proteins and
A
utoantibody
P
ositive form of
H
emolytic
U
remic
S
yndrome represents a novel subtype of hemolytic uremic syndrome ...(HUS) with unique characteristics. It affects children and requires special clinical attention in terms of diagnosis and therapy. DEAP-HUS and other atypical forms of HUS share common features, such as microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia. However, DEAP-HUS has the unique combination of an acquired factor in the form of autoantibodies to the complement inhibitor Factor H and a genetic factor which, in most cases, is the chromosomal deletion of a 84-kbp fragment within human chromosome 1 that results in the absence of the CFHR1 and CFHR3 proteins in plasma. Special attention is required to diagnose and treat DEAP-HUS patients. Most patients show a favorable response to the reduction of autoantibody titers by either plasma therapy, steroid treatment, and/or immunosuppression. In addition, in those DEAP-HUS patients with end-stage renal disease, the reduction of autoantibody titers prior to transplantation is expected to prevent post-transplant disease recurrence by aiming for full complement control at the endothelial cell surface in order to minimize adverse complement and immune reactions.
Effect of renal transplantation in childhood on longitudinal growth and adult height.
Severe growth failure is frequently observed in children suffering from end-stage renal disease (ESRD).
We ...analyzed the effect of renal transplantation (RTx) on longitudinal growth and final height in 37 children (19 girls) with ESRD with a mean follow-up of 8.5 years. The mean age at RTx was 11.3 years.
In children transplanted before start of puberty, mean height velocity increased significantly from 4.9 to 8.0 cm/year (P < 0.01), resulting in an increase in standardized height of 0.6 SD within two years post RTx. Although peak height velocity during puberty was significantly increased compared with healthy children, total pubertal height gain was reduced by 20% because of its shortened duration. Mean standardized height significantly increased from the time of RTx until final height by 1.3 SD and 0.7 SD in children transplanted before and after start of puberty, respectively. Mean adult height (boys 170 cm; girls 151 cm) was normal (>-2 SD) in 68% of patients. Change in standardized height from RTx until adult height was associated with initial degree of stunting and glomerular filtration rate (GFR; cumulative r2 0.49). Total pubertal height gain was associated with the age at start of puberty, GFR, and age at RTx (cumulative r2 0.57).
RTx in children with ESRD induces moderate catch-up growth during the prepubertal growth period. However, final height is reduced in about one third of patients due to the reduced pubertal height gain and preexisting height deficit at the time of RTx.
Serum fetuin-A has been shown to be a strong risk marker for myocardial infarction/stroke in the general population, and has been associated with vascular calcifications in patients with chronic ...kidney disease. Although these issues are worthy of being addressed in children and adolescents as well, adequate age- and gender-related reference values are missing.
Within a healthy paediatric population (n = 246), fetuin-A serum concentrations were determined (ELISA kit; Epitope Diagnostics, San Diego, CA, USA) essentially as described by the manufacturer. At the same time, serum protein and serum albumin were measured with established procedures (Beckman Coulter Inc., Krefeld, Germany). Subjects were stratified according to age (<1 yr n = 25, > or =1 and <6 yr n = 65, > or =6 and <12 yr n = 66, > or =12 yr and <16 n = 45 and > or =16 yr n = 45), and both genders were equally distributed within each age cohort.
Within each age cohort, fetuin-A serum concentrations were normally distributed, independent of age and gender and the respective reference range (mean +/- 1.96 SD) is 0.22-0.70 g/L (0.46 +/- 0.24 g/L).
Fetuin-A serum concentrations are independent of age and gender in a healthy paediatric population and are well comparable with those determined in adults with the same assay.
The extracellular protein fetuin-A is a potent soluble inhibitor of calcification, and its deficiency has been associated with vascular calcification in dialysis patients. In proteinuric patients, ...significant urinary losses of fetuin-A may cause low serum fetuin-A levels.
In a cross-sectional study, urinary/serum concentrations of fetuin-A were investigated in proteinuric children with glomerular diseases and preserved renal function (n = 58) in comparison to healthy controls (n = 246).
Mean fetuin-A serum concentrations were clearly reduced in children with nephrotic syndrome (0.25 ± 0.14 g/l, p < 0.001), slightly reduced in children with large proteinuria (0.39 ± 0.15 g/l, p < 0.05), and comparable to controls in those with mild proteinuria (0.45 ± 0.14 vs. 0.46 ± 0.12 g/l). Fetuin-A was positively correlated with serum protein (r = 0.58), albumin (r = 0.57), and calcium (r = 0.64), but negatively correlated with proteinuria (r = -0.41), albuminuria (r = -0.46), and urinary fetuin-A excretion (r = -0.48; each p < 0.001). The fractional excretion of fetuin-A was significantly associated with the degree of proteinuria and serum fetuin-A levels. However, the urinary loss of fetuin-A and albumin in nephrotic children differed by three orders of magnitude and the mean fractional excretion of fetuin-A was only 1/10 of that of albumin (0.016 ± 0.029 vs. 0.162 ± 0.403%; p < 0.001).
Fetuin-A is clearly reduced in children with nephrotic syndrome and associated with the degree of hypoalbuminemia. This is due to urinary fetuin-A loss and/or reduced hepatic synthesis. Persistent fetuin-A deficiency may have an impact on cardiovascular morbidity in nephrotic children.
This study assessed the long-term renoprotective effect of intensified blood-pressure control among children receiving a fixed high dose of an angiotensin-converting–enzyme inhibitor. Intensified ...blood-pressure control, achieved with additional medication, to reach a targeted 24-hour blood pressure in the low range of normal appeared to confer a substantial benefit with respect to a delay in the progression of renal disease among children with chronic kidney disease. However, reappearance of proteinuria after initial successful pharmacologic control was common.
Intensified blood-pressure control to reach a targeted 24-hour blood pressure in the low range of normal appeared to confer a substantial benefit with respect to a delay in the progression of renal disease among children with chronic kidney disease. However, reappearance of proteinuria was common.
Among both adults and children, chronic kidney disease tends to progress to end-stage renal failure, which is a major clinical problem. Systemic hypertension and glomerular hyperfiltration lead to progressive nephron damage.
1
–
3
Effective blood-pressure control delays the progression of renal disease in adults with chronic kidney disease, and antihypertensive agents that inhibit the renin–angiotensin system provide superior renoprotection, owing to their additional antiproteinuric, antiinflammatory, and antifibrotic properties.
4
–
7
Children comprise less than 1% of the total population with chronic kidney disease and often have congenital kidney malformations, urinary tract disorders, or genetic disorders that affect nephron formation or function. Hypertension . . .
Background. In May and June 2011 the largest known outbreak of hemolytic uremic syndrome (HUS) occurred in northern Germany. Because, quite unusually, a large number of adults was affected and the ...causative Escherichia coli strain, serotype O104:H4, showed an atypical virulence factor pattern, it was speculated that this outbreak was associated with an aggressive course and an unfavorable prognosis also in children. Methods. Retrospective analysis of medical records of 90 children and comparison to previous outbreak and sporadic case series. Results. Median age was unusually high (11.5 years) compared with that in historical series. Only 1 patient (1.1%) died in the acute phase. Most patients (67/90 74%) received supportive care only. Renal replacement therapy was required in 64 of 90 (71%) of the children. Neurological complications, mainly seizures and altered mental stage, were present in 23 of 90 (26%) patients. Ten patients received plasmapheresis, 6 eculizumab, and 7 a combination of both. After a median follow-up of 4 months, renal function normalized in 85 of 90 (94%) patients, whereas 3 patients had chronic kidney disease stage 3 or 4, and 1 patient (1.1%) still requires dialysis. Complete neurological recovery occurred in 18 of 23 patients. Mild to moderate and major residual neurological changes were present in 3 patients and 1 patient, respectively, although all patients were still improving. Conclusions. E. coli O104:H4 caused the largest HUS outbreak in children reported in detail to date and most patients received supportive treatment only. Initial morbidity, as well as short-term outcome, due to this pathogen, is comparable to previous pediatric series of Shiga toxin—producing E. coli HUS.
WT1 mutations cause a wide spectrum of renal and extrarenal manifestations. Here we evaluated disease prevalence, phenotype spectrum, and genotype–phenotype correlations of 61 patients with ...WT1-related steroid-resistant nephrotic syndrome relative to 700 WT1-negative patients, all with steroid-resistant nephrotic syndrome. WT1 patients more frequently presented with chronic kidney disease and hypertension at diagnosis and exhibited more rapid disease progression. Focal segmental glomerulosclerosis was equally prevalent in both cohorts, but diffuse mesangial sclerosis was largely specific for WT1 disease and was present in 34% of cases. Sex reversal and/or urogenital abnormalities (52%), Wilms tumor (38%), and gonadoblastoma (5%) were almost exclusive to WT1 disease. Missense substitutions affecting DNA-binding residues were associated with diffuse mesangial sclerosis (74%), early steroid-resistant nephrotic syndrome onset, and rapid progression to ESRD. Truncating mutations conferred the highest Wilms tumor risk (78%) but typically late-onset steroid-resistant nephrotic syndrome. Intronic (KTS) mutations were most likely to present as isolated steroid-resistant nephrotic syndrome (37%) with a median onset at an age of 4.5 years, focal segmental glomerulosclerosis on biopsy, and slow progression (median ESRD age 13.6 years). Thus, there is a wide range of expressivity, solid genotype–phenotype associations, and a high risk and significance of extrarenal complications in WT1-associated nephropathy. We suggest that all children with steroid-resistant nephrotic syndrome undergo WT1 gene screening.
Children requiring kidney replacement therapy experience high burden of cardiovascular (CV) disease leading to increased mortality. Intima-media thickness (IMT) indicating atherosclerosis is a ...validated surrogate marker for future CV events.
We investigated the effect of different treatment modalities (dialysis, preemptive kidney transplantation (KTx), late KTx after dialysis) on IMT by multivariable linear mixed-effect modeling. Patients were enrolled in a prospective cohort study.
A total of 261 analyzed children had a mean follow-up of 3 y. Children after preemptive and late KTx had lower levels of IMT when compared with dialysis. Using an interaction term, a significant progression of IMT over time was seen during dialysis (β = 0.0053 mm/y, P = 0.004). IMT before the start of therapy was the most influential determinant in all models. Low IMT was associated with maintenance steroid treatment after preemptive KTx. High IMT on dialysis was associated with higher systolic blood pressure, lower body mass index, lower serum albumin, and lower bicarbonate.
IMT remained rather stable in children several years after KTx. In contrast, children on dialysis had higher IMT values, which increased over time. In these children, blood pressure control, calorie and protein intake, and acid-base homeostasis seem important. Taken together, children might profit from early transplantation to limit accumulation of CV risk.
PDF
