Pediatrics and Neonatology最新文献

Alport syndrome (AS) is the second common monogenic cause of end-stage kidney disease (ESKD) worldwide and is caused by defective type 4 collagen due to pathogenic variants of COL4A3, COL4A4, or COL4A5. Type 4 collagen also exists in the eyes and ears, and thus ocular defects and hearing loss occur in AS. The understanding of AS has expanded over the past two decades due to greater availability of genetic testing and research on genotype-phenotype correlation. Patients previously diagnosed with idiopathic steroid resistant nephrotic syndrome or ESKD of unknown etiology may now be diagnosed as AS if pathogenic COL4A3-5 variants are identified. Some carriers of heterozygous COL4A3-5 variants may now be classified into females with X-linked AS or autosomal dominant AS, if there are typical pathologic changes in the glomerular basement membrane or if there is proteinuria and progression of kidney disease. Lastly, it has been recommended that renin-angiotensin-aldosterone system inhibition be started as soon as possible for selected AS patients for its long-term protective effect against kidney function deterioration. The purpose of this review is to introduce these important concepts to general pediatricians and pediatric nephrologists.

Emerging antenatal risk factors have been associated with an increased risk of kidney disease throughout the offspring's life course. However, the intricate kidney programming mechanisms underlying these risks remain complex and are incompletely understood, but they are rooted in structural and functional alterations within the kidneys. The Developmental Origins of Health and Disease (DOHaD) theory underscores the significance of elucidating core mechanisms initiated through the maternal-fetal interface, which trigger kidney programming. Furthermore, it offers a promising avenue for preventing kidney disease at its earliest stages through a process known as reprogramming. This concise review aims to synthesize existing knowledge regarding the impact of kidney programming on offspring kidney disease and to provide an overview of documented reprogramming strategies as observed in animal models of kidney programming. By consolidating this information, we aim to expedite the translation of research breakthroughs into practical clinical solutions, ultimately resulting in enhanced outcomes for children facing kidney-related issues.

Idiopathic nephrotic syndrome (INS) is a relatively common renal disorder of childhood characterized by severe proteinuria and associated hypoproteinemia and edema. Although the pathogenesis of INS remains unknown, the prevailing theory of its pathogenesis is as follows. Antigenic stimulation, such as viral infections or vaccines, in children with susceptibility factors for INS triggers abnormal immune responses, resulting in production of pathogenic substances that injure podocytes (renal glomerular epithelial cells). The injured podocytes then change their function and morphology, resulting in increased permeability of plasma proteins. Consequently, plasma proteins, especially albumin, are leaked into urine and massive proteinuria ensues. Research on susceptibility factors for INS has focused on polymorphisms in several genes including human leukocyte antigen class II genes. However, we propose that dysbiosis of the intestinal microbiota could be a susceptibility factor for relapse. This proposal is based on our research group finding that children with INS and frequent relapses have gut dysbiosis characterized by a decreased proportion of beneficial bacteria such as short-chain fatty acid-producing bacteria. Dysbiosis from the neonatal period to infancy may result from environmental factors, such as cesarean section delivery and antibiotic administration, which prevent the establishment of a normal intestinal microbiota. Dysbiosis leads to aberrant gut immunity and is characterized by a decreased ratio of T helper 1 cells/T helper 2 cells and an increased ratio of T helper 17 cells/regulatory T-cells. Therefore, relapse occurs when immunologically pathogenic factors that injure podocytes are produced in response to trigger events in children with INS and gut dysbiosis. Our recent clinical trial suggested that long-term oral administration of butyric acid-producing bacterium as a probiotic is promising for suppressing relapse. Therefore, studying the causal relationship between dysbiosis and relapses in patients with INS in a larger number of patients is necessary.

Background: Some infants with urinary tract infection (UTI) may exhibit concurrent bacteremia, potentially leading to septic shock or bacterial meningitis. Identifying risk factors for bacteremia in infants with UTI is crucial for prompt intervention to prevent subsequent adverse outcomes.

Methods: Between 2015 and 2021, a total of 632 infants with UTI aged ≤12 months were enrolled at Kaohsiung Veterans General Hospital (KSVGH), among whom 20 had concurrent bacteremia. We analyzed their differences in outcomes and demographic, clinical, and laboratory characteristics. Independent risk factors for bacteremic UTI were identified using binary logistic regression analysis.

Results: A positive underlying disease (including congenital anomalies of kidney and urinary tract [CAKUT] and prematurity), C-reactive protein (CRP) > 8 mg/dL, lower body weight, and positive urinary nitrite were independent risk factors for infants with UTI and bacteremia.

Conclusions: Physicians should be mindful of the potential for bacteremia to develop in infants with UTI, particularly those with concurrent positive underlying diseases or CRP >8 mg/dL.