Clinical outcomes and clinico-pathological correlations in children with MPO-ANCA-associated glomerulonephritis showing renal arteritis.

The aim of this study was to evaluate the clinical features, pathological characteristics, and prognosis in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) with renal arteritis. The study involved 97 children from five pediatric clinical centers with MPO-AAGN who exhibited distinct clinical features. The patients were divided into AAGN-A+ and AAGN-A-, based on the presence or absence of arteritis, and the disparities in clinical, histopathological characteristics, and prognosis between the two groups was evaluated. In contrast to the AAGN-A- group, the children in the AAGN-A+ group exhibited more pronounced clinical symptoms and renal pathological injury. Arteritis positively moderately correlated with the serum creatinine, interleukin-6, urinary neutrophil gelatinase-associated lipocalin, negatively moderately correlated with serum complement C3. The renal survival rate in the AAGN-A+ group was significantly poorer than AAGN-A- group (χ2 = 4.278, p = 0.039). Arteritis showed a good predictive value for end-stage kidney disease (ESKD), and C3 deposition, ANCA renal risk score and arteritis were independent risk factors for the development of ESKD in children with MPO-AAGN. Arteritis is a significant pathological change observed in children with MPO-AAGN, and the formation of arteritis may be related to the inflammatory response and activation of the complement system.

Bowman capsule rupture in children with myeloperoxidase-antineutrophil cytoplasmic antibody-associated glomerulonephritis predicts poor renal survival.

Background: Recent developments indicated that Bowman capsule rupture (BCR) is observed in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). We aimed to explore the relationship between BCR and clinical manifestations, pathological changes, and prognosis in children with myeloperoxidase (MPO)-AAGN. Methods: A total of 56 children with MPO-AAGN were divided into BCR (+) and BCR (-) groups according to the status of Bowman's capsule. Clinical and histological features and renal outcomes were compared, and the predictive value of BCR for end-stage kidney disease (ESKD) of MPO-AAGN was evaluated. Results: After retrospective analysis of the data, 24 children (42.9%) were found to have BCR. The results showed that BCR positively correlated with intrarenal immune cell infiltrates, obsolescence and crescents in glomeruli, tubulointerstitial inflammation, tubulitis, and tubular atrophy negatively correlated with normal glomeruli and immunoglobulin G deposition in the kidney. The clinical features and kidney pathological changes were more severe in the BCR (+) group than BCR (-) group, and the renal survival rate was significantly poorer in the BCR (+) group than BCR (-) group (χ2 = 5.45, p = 0.02). Moreover, estimated glomerular filtration rate (≤15 mL/min/1.73 m2), BCR and ANCA renal risk score (ARRS) were independent risk factors for the development of ESKD in children with MPO-AAGN. After combining BCR with the Berden classification and ARRS, our data suggested that the Berden classification + BCR and ARRS + BCR showed better predictive values for ESKD than those of the Berden classification and ARRS, respectively. Conclusion: BCR is an important pathological lesion that correlates with severe clinical manifestations, pathological changes, and poor prognosis in children with MPO-AAGN.

The effect of levetiracetam and oxcarbazepine monotherapy on thyroid hormones and bone metabolism in children with epilepsy: A prospective study.

BACKGROUND: Long-term treatment with certain antiepileptic drugs may lead to thyroid function disturbances or alterations in bone metabolism; the data on the effects of new antiepileptic drugs on this are limited and conflicting, especially in children with epilepsy. Therefore, the aim of this study was to investigate the effects of levetiracetam and oxcarbazepine on thyroid hormone levels and bone metabolism in children with epilepsy. METHODS: A total of 51 children with new-onset partial epilepsy were selected. They were randomly treated with either levetiracetam (n = 25), or oxcarbazepine (n = 26) monotherapy. Eight of the 51 patients were excluded for failing to take the drug continuously or failing to undergo a regular review. Thus, 43 patients were finally included (levetiracetam: 23 patients, oxcarbazepine: 20 patients). A control group consisting of age- and sex-matched healthy subjects (n = 20) was included for comparison. Serum triiodothyronine, tetraiodothyronine, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, calcium, phosphorus, alkaline phosphatase, osteocalcin, parathyroid hormone, and 25-hydroxyvitamin D levels and bone mineral density values were measured before and at 6 and 12 months after therapy in all groups. RESULTS: At baseline, thyroid hormone levels, bone metabolism index, and bone mineral density values did not differ between the control group and the drug-treated groups. Levetiracetam-treated patients showed no significant changes in thyroid hormone levels, bone metabolism, and bone mineral density during the 12-month follow-up period compared with baseline values. In the oxcarbazepine group, compared to baseline values, serum free thyroxine levels decreased after 12 months of treatment (Z = -3.115, p = 0.002), and after 6 and 12 months of treatment, calcium levels decreased (Z = -3.705, p < 0.001 and Z = -3.884, p < 0.001, respectively) and parathyroid hormone levels increased (Z = -3.698, p < 0.001 and Z = -3.921, p < 0.001, respectively); however, all other parameters did not differ from baseline values. CONCLUSION: Our data show that levetiracetam treatment has no significant effect on thyroid function and bone metabolism in children with epilepsy. Long-term use of oxcarbazepine may reduce serum free thyroxine levels, resulting in impaired thyroid function, and may reduce serum calcium and increase parathyroid hormone levels, leading to bone metabolism disorders.

Risk factors for arterial ischemic and hemorrhagic stroke in childhood.

This study assessed potential etiologies of arterial ischemic stroke and hemorrhagic stroke among children of Mainland China. From January 1996-June 2006, 251 patients with consecutive childhood stroke (aged 1 month through 16 years) were admitted to Beijing Children's Hospital. Arterial ischemic stroke accounted for the majority of cases (62.5%). Idiopathic stroke (32.5%) was more common than cardiac stroke (8.9%), vascular or arteriopathic stroke (21.0%), hematologic disorder-associated stroke (10.8%), and other etiologies (26.8%). Vitamin K deficiency was a major etiology in 72 of 94 hemorrhagic strokes (76.6%), most of which occurred in breastfeeding infants (80.6%) and those who received no vitamin K after birth (73.6%). Arteriovenous malformation (6.4%) was a frequent etiology in the remaining hemorrhagic stroke cases. We found that ischemic stroke in children is more common than hemorrhagic stroke, and many cases of ischemic stroke are idiopathic. Vitamin K deficiency was a major etiology in these young infants who experienced hemorrhagic stroke.

Role of TNF-alpha gene variation in idiopathic childhood ischemic stroke: a case-control study.

Etiology of the idiopathic childhood stroke remains unknown. In previous studies, the immunologic process may be involved in the idiopathic stroke. Tumor necrosis factor- alpha (TNF-alpha), an important immune mediator, may contribute to the initiation and progression in the stroke. The main purpose of this study was to investigate correlation of TNF-alpha genetic variation and idiopathic childhood ischemic stroke. Using the direct DNA sequencing method, polymorphisms in the TNF-alpha promoter region were genotyped in 67 Chinese patients with idiopathic childhood stroke and 70 controls. Among totally 7 single nucleotide polymorphisms identified in the TNF-alpha promoter region, the variant of the -863C/A is associated with increased risk of idiopathic childhood ischemic stroke in our study group. TNF-alpha molecule may have genetically as well as functionally an important role in the pathogenesis of idiopathic childhood ischemic stroke in the Chinese population.

Arterial ischemic stroke: experience in Chinese children.

The aim of this study was to review cases of pediatric arterial ischemic stroke among Chinese subjects and thereby evaluate risk factors, clinical and neuroimaging features, and treatment, to establish a reasonable guideline for assessment and management of the disease. Between 1996 and 2006, 157 children (male:female ratio, 1.4:1) with arterial ischemic stroke were identified at Beijing Children's Hospital. The median age at stroke was 32 months (range, 4-192). Among patients with determined etiology, infections (12.1%), moyamoya disease (12.1%), and trauma (10.8%) were the most common. In 51 patients, there were no obvious risk factors (32.5%). Hemiplegia was the most common presenting feature (81.5%). The region of left middle cerebral artery was most frequently affected (36.3%), followed by the right middle cerebral artery (29.9%). Of the 157 patients, 56 were treated by intravenous thrombolytic agents (35.7%), all but one of them successfully (the one exception involving hemorrhagic complication). Randomized controlled trials are needed to establish primary prevention, acute treatment, and secondary prevention of pediatric ischemic stroke.

[Association between vitamin D receptor gene polymorphism and the susceptibility of children to lead].

OBJECTS: To investigate the distribution of vitamin D receptor (VDR) genotypes among the Hans of a lead contaminated mine in Shanxi and explore the relationship between blood lead levels and the genetic polymorphism of VDR gene. METHODS: VDR genotypes were determined by polymerase-chain-reaction and restrictive fragment length polymorphism (PCR-RFLP) and the blood lead level was measured by using the graphite furnace atomic absorption spectrometry in a population of 120 pre-school children aged 5 - 6 years who were from the mine kindergarten and were unrelated Hans. An environmental questionnaire in relation to blood lead level was filled for each subject. RESULTS: (1) The gene distribution of the VDR phenotypes in these children was VDRBB, 1.7%; VDRBb, 9.2%; VDRbb, 89.2%. (2) The mean blood lead level of the children who had VDR B allele [(0.910 8 +/- 0.265 0) micromol/L] was significantly higher than that whose VDR genotype was bb [(0.740 1 +/- 0.270 1) micromol/L (mean +/- standard deviation)] (t = 2.155, P < 0.05). (3) Many factors were found to affect the blood lead levels, such as the VDR genotype, the type of fuel, educational level of mothers and so on. After controlling the possible confounding variables by multiple regression, the contribution of the VDR phenotype to the blood lead levels was still statistically significant. CONCLUSION: These results indicated that the frequency distribution of the VDR genotype in these children was apparently different from that in Caucasians who had high frequencies of VDR B. The results also indicated that the individuals carrying the VDR B allele were more susceptible to lead poisoning.