Pediatric Reference Change Value Optimized for Acute Kidney Injury: Multicenter Retrospective Study in China.

OBJECTIVES: The standard definition of pediatric acute kidney injury (AKI) is evolving, especially for critically ill in the PICU. We sought to validate the application of the Pediatric Reference Change Value Optimized for Acute Kidney Injury in Children (pROCK) criteria in critically ill children. DESIGN: Multicenter retrospective study. SETTING: Six PICUs in mainland China. PATIENTS: One thousand six hundred seventy-eight hospitalized children admitted to the PICU with at least two creatinine values within 7 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKI was diagnosed and staged according to the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE), the Kidney Disease Improving Global Outcomes (KDIGO), and the pROCK criteria. Multiple clinical parameters were assessed and analyzed along with 90-day follow-up outcomes. According to the definitions of pRIFLE, KDIGO, and pROCK, the prevalence of AKI in our cohort of 1,678 cases was 52.8% (886), 39.0% (655), and 19.0% (318), respectively. The presence of AKI, as defined by pROCK, was associated with increased number of injured organs, occurrence of sepsis, use of mechanical ventilation, use of continuous renal replace therapy ( p < 0.05), higher Pediatric Risk of Mortality III score, and higher Pediatric Logistic Organ Dysfunction-2 score ( p < 0.001). The survival curve of 90-day outcomes showed that pROCK was associated with shorter survival time (LogRank p < 0.001), and pROCK definition was associated with better separation of the different stages of AKI from non-AKI ( p < 0.001). CONCLUSIONS: In this retrospective analysis of AKI criteria in PICU admissions in China, pROCK is better correlated with severity and outcome of AKI. Hence, the pROCK criteria for AKI may have better utility in critically ill children.

A Novel Mutation c.841C>T in COPA Syndrome of an 11-Year-Old Boy: A Case Report and Short Literature Review.

COPA syndrome is a rare autosomal dominant disorder with auto-immune and auto-inflammatory abnormalities. This disease is caused by mutations of COPα, a protein that functions in the retrograde transport from the Golgi to the ER. Here we report the first COPA case of an 11-year-old boy with c.841C>T, p.R281W mutation. The arginine at position 281 was located in a highly evolutionary-conserved region. Immunosuppressive drugs and corticosteroids might not improve the long-term outcome of COPA patients. For patients with pulmonary disease, polyarthritis and/or kidney disorder, and suspected of COPA, genetic analysis should be conducted promptly for early diagnosis.

Computational Systems Pharmacology, Molecular Docking and Experiments Reveal the Protective Mechanism of Li-Da-Qian Mixture in the Treatment of Glomerulonephritis.

BACKGROUND: Glomerulonephritis is a common urinary system disease among children. Growing evidence suggests that traditional Chinese medicine has potential in treating glomerulonephritis, such as Li-Da-Qian mixture. Although its anti-glomerulonephritis and alleviating hematuria effects have been reported, the exact mechanism of Li-Da-Qian mixture devoting to glomerulonephritis remains unexplored. It was necessary to explore the mechanism of Li-Da-Qian mixture against glomerulonephritis using modern technology, such as Chinese medicine database and molecular biological experiments. METHODS: Online databases were used to look up ingredients and predict targets of Li-Da-Qian mixture against glomerulonephritis. The intersecting targets of Li-Da-Qian mixture and glomerulonephritis were selected for enrichment analysis. Cytoscape software was applied to establish network and MCODE analysis. Molecular docking was used for the primary validation. Furthermore, we examined the function of the core compounds analyzed from Li-Da-Qian mixture to rescue LPS-induced inflammation in vivo and vitro. We also explored whether the core compounds can alleviate TGFß1-induced renal fibrosis in mouse proximal tubular cells. RESULTS: Network pharmacological analysis of Li-Da-Qian evaluated 20 active ingredients including baicalein, luteolin and quercetin. A total of 113 key targets were screened, including IL6, VEGFA, TP53, EGF, MMP2, etc, and they were enriched in AGE-RAGE signaling pathway in diabetic complications, TNF and IL-17 signaling pathways. Moreover, the core ingredients succeeded in binding to the main targets via molecular docking, further identifying the anti-glomerulonephritis effects and improvement of vascular injury. Western blotting and qPCR also suggested that baicalein and luteolin can improve inflammation and restore disturbance of mesangial cells or kidney induced by LPS. In addition, baicalein and luteolin inhibited renal fibrosis in vitro.

A Synonymous Variant c.579A>G in the ETFDH Gene Caused Exon Skipping in a Patient With Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency: A Case Report.

Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder characterized by a wide range of clinical features, including muscle weakness, hypoglycemia, metabolic acidosis, and multisystem dysfunctions. Loss-of-function mutations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene are associated with MADD. Disease-causing synonymous variants in the ETFDH gene have not been reported so far. Methods: We reported the clinical course of a Chinese girl who was diagnosed with late-onset MADD by the whole exome sequencing. The effects of variants on mRNA splicing were analyzed through transcript analysis in vivo and minigene splice assay in vitro. Results: The 6-month-old girl initially showed muscle weakness, muscular hypotonia, mild myogenic damage, and fatty liver. The blood and urine metabolic screening by tandem mass spectrometry suggested MADD. Molecular analysis of ETFDH gene revealed two novel heterozygous variants, a frameshift mutation c.1812delG (p.V605Yfs*34) in exon 13 and a synonymous variant c.579A>G (p.E193E) in exon 5. The transcript analysis in vivo exhibited that the synonymous variant c.579A>G caused exon 5 skipping. The minigene splice assay in vitro confirmed the alteration of ETFDH mRNA splicing which could lead to the production of a truncated protein. Supplementation of riboflavin, carnitine and low-fat diet improved the clinical symptoms. Conclusion: We firstly report a rare case of MADD with a pathogenic synonymous variant in the ETFDH gene which highlights the importance and necessity of bioinformatic analysis and functional testing for synonymous variants when searching for causative gene mutations. The results expand the spectrum of pathogenic variants in MADD.