Background. In 2011 Escherichia coli O104:H4 caused an outbreak with >800 cases of hemolytic uremic syndrome (HUS) in Germany, including 90 children. Data on the intermediate outcome in children ...after HUS due to E. coli O104:H4 have been lacking. Methods. Follow-up data were gathered retrospectively from the medical records of patients who had been included in the German Pediatric HUS Registry during the 2011 outbreak. Results. Seventy-two of the 89 (81%) patients were included after a median follow-up of 3.0 (0.9–4.7) years. Hypertension and proteinuria were present in 19% and 28% of these patients, respectively. Of 4 patients with chronic kidney disease (CKD) > stage 2 at short-term follow-up, 1 had a normalized estimated glomerular filtration rate, and 3 (4%) had persistent CKD > stage 2. In 1 of these patients, CKD improved from stage 4 to 3; 1 who had CKD stage 5 at presentation received kidney transplantation; and 1 patient required further hemodialysis during follow-up. One patient (1.4%) still had major neurological symptoms at the latest follow-up. Dialysis during the acute phase (P = .01), dialysis duration (P = .01), and the duration of oligo-/anuria (P = .005) were associated with the development of renal sequelae. Patients treated with eculizumab (n = 11) and/or plasmapheresis (n = 13) during the acute phase of HUS had comparable outcomes. Conclusions. The overall outcome of pediatric patients after HUS due to E. coli O104:H4 was equivalent to previous reports on HUS due to other types of Shiga toxin–producing E. coli (STEC). Regular follow-up visits in patients are recommended after STEC-HUS.
Hereditary defects of coenzyme Q10 biosynthesis cause steroid-resistant nephrotic syndrome (SRNS) as part of multiorgan involvement but may also contribute to isolated SRNS. Here, we report 26 ...patients from 12 families with recessive mutations in ADCK4. Mutation detection rate was 1.9% among 534 consecutively screened cases. Patients with ADCK4 mutations showed a largely renal-limited phenotype, with three subjects exhibiting occasional seizures, one subject exhibiting mild mental retardation, and one subject exhibiting retinitis pigmentosa. ADCK4 nephropathy presented during adolescence (median age, 14.1 years) with nephrotic-range proteinuria in 44% of patients and advanced CKD in 46% of patients at time of diagnosis. Renal biopsy specimens uniformly showed FSGS. Whereas 47% and 36% of patients with mutations in WT1 and NPHS2, respectively, progressed to ESRD before 10 years of age, ESRD occurred almost exclusively in the second decade of life in ADCK4 nephropathy. However, CKD progressed much faster during adolescence in ADCK4 than in WT1 and NPHS2 nephropathy, resulting in similar cumulative ESRD rates (>85% for each disorder) in the third decade of life. In conclusion, ADCK4-related glomerulopathy is an important novel differential diagnosis in adolescents with SRNS/FSGS and/or CKD of unknown origin.
Summary
Epstein‐Barr virus (EBV) primary infection constitutes a serious risk for pediatric transplant recipients, particularly as regards the development of EBV‐related post‐transplant ...lymphoproliferative disease (PTLD). Currently, there is no established prophylactic regimen. We investigated the association between chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) and the incidence of EBV viremia in EBV‐naïve pediatric renal transplant recipients (R−) who had received a graft from an EBV‐positive donor (D+) and are therefore at high risk of EBV primary infection. In a prospective, multicenter trial (n = 114), we compared a cohort on chemoprophylaxis (n = 20) with a similar control cohort without chemoprophylaxis (n = 8). Over the 1‐year study period, antiviral prophylaxis with VGCV/GCV was associated with a significantly decreased incidence of EBV primary infection: 9/20 patients (45%) in the prophylaxis group experienced an EBV primary infection compared to 8/8 controls (100%) (P < 0.0001). Chemoprophylaxis was associated with a significantly lower EBV viral load (P < 0.001). Type or intensity of immunosuppressive therapy did not influence the occurrence of EBV primary infection or the level/persistence of EBV viral load. Chemoprophylaxis with VGCV/GCV is associated with a reduced incidence of EBV viremia in high‐risk pediatric kidney allograft recipients in the first year post‐transplant.
(ClinicalTrials.gov number: NCT00963248).
Background
Because infections constitute a major cause of morbidity and mortality in paediatric renal allograft recipients, avoidance of preventable systemic infections by vaccination before ...transplantation is of utmost importance. However, data on the completeness of vaccinations and factors associated with incomplete vaccination coverage are scarce.
Methods
Within the framework of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN), we therefore performed a multi-centre, multi-national, retrospective study investigating the vaccination coverage before transplantation of 254 European children with end-stage renal disease (mean age 10.0 ± 5.6 years).
Results
Only 22 out of 254 patients (8.7%) presented complete vaccination coverage. In particular, the respective vaccination coverage against human papillomavirus (27.3%), pneumococci (42.0%), and meningococci (47.9%) was low. Patients with complete pneumococcal vaccination coverage had numerically less lower respiratory tract infections during the first 3 years post-transplant than children without vaccination or with an incomplete status (16.4% vs 27.7%,
p
= 0.081). Vaccine-preventable diseases post-transplant were 4.0 times more frequently in unvaccinated than in vaccinated patients. Factors associated with an incomplete vaccination coverage were non-Caucasian ethnicity (OR 9.21,
p
= 0.004), chronic dialysis treatment before transplantation (OR 6.18,
p
= 0.001), and older age at transplantation (OR 1.33,
p
< 0.001).
Conclusions
The vaccination coverage in paediatric kidney transplant candidates is incomplete. Paediatric nephrologists, together with primary-care staff and patients’ families, should therefore make every effort to improve vaccination rates before kidney transplantation.
The efficacy and acceptability of cinacalcet for treatment of secondary hyperparathyroidism (SHPT) was assessed in seven pediatric patients suffering from end-stage renal disease (ESRD) presenting ...with inadequately controlled SHPT despite conventional management. Patients received daily treatment with cinacalcet (dosage 0.25 mg/kg body weight) for a total of 4 weeks. Within 4 h after application of the first dose, median levels of serum parathyroid hormone (PTH) had decreased from 932 pg/ml (range 511–1,938 pg/ml) to 584 pg/ml (88–937 pg/ml), and final pre-dose values after 4 weeks were 199 pg/ml (121–940 pg/ml; each
P
< 0.05 versus baseline). Median concentrations of serum calcium (Ca) decreased within 4 h of the first administration, from 2.56 mmol/l to 2.38 mmol/l, returning to 2.58 mmol/l at 24 h, and they remained slightly decreased compared to baseline values thereafter (each
P
< 0.05 versus baseline). Both the median levels of serum phosphorus (P) and the Ca × P ion product decreased significantly during the 4-week period. Cinacalcet was well tolerated and without drug-related adverse effects. Thus, even with approximately half of the dose usually given to adult dialysis patients, PTH and the Ca × P ion product were markedly reduced in pediatric ESRD patients presenting with inadequately controlled SHPT. Therefore, our results support the initiation of a randomized, controlled, long-term trial in children.
Fetuin-A and vitamin D are significant correlates of cardiovascular morbidity in paediatric chronic kidney disease (CKD) patients. It is thus far unknown, whether or not serum fetuin-A is affected by ...the vitamin D status or treatment with vitamin D preparations in these patients.
In a cross-sectional study, serum concentrations of fetuin-A, 25-hydroxyvitamin D(3) (25OHD) and 1,25-dihydroxyvitamin D(3) (calcitriol) levels were determined in 112 paediatric patients with mild-to-severe CKD (Stages 1-5) and after renal transplantation. A25OHD supplementation and/or calcitriol treatment were given in 64% of the patients.
Fetuin-A levels were clearly reduced in dialysis patients but were comparable to healthy controls in those with moderate CKD and after transplantation. Although 64 and 46% of all patients received 25OHD and/or calcitriol treatment, 48 and 20% of patients were 25OHD and/or calcitriol deficient, respectively. Within the whole patient cohort, fetuin-A correlated with serum calcium and yearly weight-related 25OHD dosage (each P < 0.01) but not with the vitamin D status per se. Multiple regression analysis revealed the need for dialysis treatment and cumulative 25OHD dosage as independent predictors of fetuin-A concentrations (model r(2) = 0.17). In dialysis patients, fetuin-A was inversely correlated with serum C-reactive protein but positively correlated with cumulative calcitriol dosage and serum parathormone (each P < 0.01).
Fetuin-A levels are clearly reduced in children on dialysis but not in those with moderate CKD and after transplantation. Besides the degree of microinflammation, the cumulative intake of 25OHD and calcitriol are significantly correlated to fetuin-A in these patients. The impact of vitamin D treatment appears to be at least partly mediated by serum calcium.
Long-term survival of children and adolescents with chronic kidney disease (CKD) is mainly limited by cardiovascular disease. Pediatric CKD patients (
n
= 26) on conservative treatment, dialysis and ...after renal transplantation were compared with healthy controls (
n
= 24) with respect to cardiovascular status. Mean baseline diameter of the brachial artery was significantly higher, and mean flow-mediated vasodilation (FMD) was significantly reduced, in CKD patients. CKD patients showed significantly increased left ventricular mass index, blood pressure (BP) values and age-related values of mean carotid intima-media thickness intima-media thickness–standard deviation score (IMT-SDS) compared with those of controls. Approximately 60% of patients presented with impaired FMD (≤ 5.79%), which was significantly associated with intima-media thickening, although only three patients (12%) presented with both, impaired FMD and increased age-related IMT. The latter was significantly associated with higher values for day-time BP. In contrast, duration and degree of CKD, mode of renal replacement therapy, homocysteine levels and concomitant medication showed no association with cardiovascular status. The majority of our pediatric CKD patients showed reduced endothelial function, which may have preceded the development of carotid arteriopathy. Therefore, routine assessment of FMD may be a useful tool to identify CKD patients at risk of progressive cardiovascular morbidity.
The aim of this study was to investigate the hepatic microsomal and cytosolic functions by using the
13
CO
2
breath test in healthy subjects either before or after consumption of red wine. Twelve ...adults received
13
C
2
aminopyrine and l-1-
13
Cphenylalanine together with a standardised dinner. Expired air samples were taken over 6 h. After a wash-out period, the subjects consumed 0.4 ml ethanol per kg per day together with dinner over a 7.5-day period on average. Thereafter,
13
C-tracer administration was repeated under identical conditions. The
13
CO
2
enrichments were measured by isotope ratio mass spectrometry. The mean cumulative percentage
13
C-dose recovery after administration of
13
C
2
aminopyrine and l-1-
13
Cphenylalanine either without or with red wine consumption amounted to 17.0±4.4 vs. 14.7±3.1% (p=0.170) and 14.0±2.8 vs. 11.5±3.9% (p=0.084), respectively. Moderate alcohol consumption does not induce significant short-term changes of the microsomal and the cytosolic function of the human liver in healthy subjects.
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