A novel gain-of-function mutation in transient receptor potential C6 that causes podocytes injury.

Podocyte injury plays a vital role in focal segmental glomerulosclerosis (FSGS), and apoptosis is one of its mechanisms. The transient receptor potential channel 6 (TRPC6) is highly expressed in podocytes and mutations mediate podocyte injury. We found TRPC6 gene mutation (N110S) was a new mutation and pathogenic in the preliminary clinical work. The purpose of this study was to investigate the potential mechanism of mutation in TRPC6 (TRPC6-N110S) in the knock-in gene mouse model and in immortalized mouse podocytes (MPC5). Transmission electron microscopy was used to evaluate renal injury morphology. We measured 24-hour urinary albumin-to-creatinine ratios and major biochemical parameters such as serum albumin, urea nitrogen, and total cholesterol. The results of CCK-8 assay and apoptosis experiments showed that the TRPC6-N110S overexpression group had slower proliferative activity and increased apoptosis than the control group. FluO-3 assay revealed increased calcium influx in the TRPC6-N110S overexpression group. Podocin level was decreased in TRPC6-N110S group, while TRPC6 and desmin levels were increased in TRPC6-N110S group. The 24 h uACR at 6 weeks was significantly higher in the pure-zygotes group than in the WT and heterozygotes groups, and this difference was found at 8 and 10 weeks.TRPC6 levels showed no significant difference between homozygote and WT mice. Compared to homozygote group, expression of podocin and nephrin were increased in WT, but levels of desmin was decreased in WT. Our results suggest that this new mutation causes podocyte injury probably by enhancing calcium influx and podocyte apoptosis, accompanied by increased proteinuria and decreased expression of nephrin and podocin.

Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

Nephrotic Syndrome Complicated with Familial Hypocalciuric Hypercalcemia in an Infant: A Case Report and Comprehensive Literature Review.

Background: Nephrotic syndrome, a prevalent childhood glomerular disorder, manifests with proteinuria, hypoalbuminemia, edema, and hypercholesteremia. Hypercalcemia, though rare, occasionally complicates these cases. Familial hypocalciuric hypercalcemia, an autosomal dominant disorder, is characterized by lifelong hypercalcemia, hypocalciuria, and normal or elevated parathyroid hormone levels due to loss-of-function mutations. Case Presentation: We detail a 2-year-old girl with nephrotic syndrome whose proteinuria responded effectively to steroid therapy without side effects. Hypercalcemia emerged after one month, prompting a familial history investigation, revealing a predisposition to hypercalcemia. Genetic analysis identified a heterozygous mutation c.1394G>A (p.R465Q) in the calcium-sensing receptor gene, shared among the patient, her grandmother, her father, and one sister. Notably, hypercalcemia required no intervention. Conclusions: This case report is the first documenting familial hypocalciuric hypercalcemia in a child with primary nephrotic syndrome and delineates the familial pedigree. While familial hypocalciuric hypercalcemia is infrequent, our findings affirm its generally benign nature. A critical aspect of patient care involves monitoring for potential complications, including acute pancreatitis or chondrocalcinosis. The indispensability of genetic studies in both diagnosis and the differentiation of related conditions is underscored, emphasizing their pivotal role in enhancing our understanding of this rare yet clinically significant disease. Continued research is imperative for advancing knowledge and improving clinical management.

Targeting ferroptosis attenuates podocytes injury and delays tubulointerstitial fibrosis in focal segmental glomerulosclerosis.

Ferroptosis is a non-apoptotic form of cell death, involved in chronic kidney diseases (CKD) and acute kidney injury (AKI), so far, the role of ferroptosis in focal segmental glomerulosclerosis (FSGS) remains largely unknown. We aimed to investigate the role of ferroptosis in FSGS, in this study, we found the reduced expression of GPX4 in podocytes, as well as tubular epithelial cells (TECs), from patients with FSGS. Treatment with ferrostatin-1 (Fer-1), a potent and selective ferroptosis inhibitor, significantly reduced proteinuria, prevented glomerulosclerosis, attenuated podocyte injury in ADR-induced FSGS murine model. As expected, ADR treatment caused downregulation of GPX4 in human podocytes, treatment with Fer-1 greatly blocked the downregulation of GPX4, restored the GSH level and attenuated cell death. Furthermore, Fer-1 treatment greatly delayed the development of tubulointerstitial fibrosis in ADR-induced FSGS murine model. Taken together, ferroptosis is involved in the pathogenesis of FSGS, targeting ferroptosis is a promising therapeutic option for patients with FSGS.

Anti-C1q antibodies in lupus nephritis children with glomerular microthrombosis.

AIM: Glomerular microthrombosis (GMT) was a common vascular lesion in patients with lupus nephritis (LN). The objective of this study was to investigate the relationship between serum anti-beta2-glycoprotein I antibodies (a-ß2GP1) and anti-complement 1q antibodies (a-C1q) antibodies and to investigate the possible mechanism of GMT in children with LN. METHODS: The subjects were 191 children with LN diagnosed by renal biopsy in our hospital from January 2017 to January 2020. The patients were divided into GMT group and non-GMT group. The clinical manifestations, laboratory tests, renal pathology, prognosis of the two groups and the relationship between a-ß2GP1 and a-C1q antibodies were observed. RESULTS: In 191 children with LN, 52 cases (27.23%) presented with GMT. The value of C3, haemoglobin (Hb), estimate glomerular filtration rate (eGFR) and anticardiolipin antibody (ACA) in GMT group were lower than that of non-GMT group (p < .05, p < .01). The value of serum creatinine (Scr), 24 h proteinuria (PRO), urine red blood cells (RBC), N-acetyl-ß-d-glucosidase (NAG) and retinol-binding protein (RBP), a-C1q, a-ß2GP1, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and renal histopathological activity index (AI) score in GMT group were higher than that of non-GMT group (p < .05, p < .01). The positive proportions of serum a-C1q and a-ß2GP1 in GMT group were higher than those in non-GMT group (p < .05). According to Spearman correlation analysis, a-C1q was positively correlated with AI score, SLEDAI, a-ß2GP1, GMT, LN-III and LN-IV. Hb, eGFR and a-C1q Ab were associated with the formation of GMT in children with LN. The complete proteinuria remission and renal survival in GMT group were significantly lower than those in non-GMT group (p < .05, p < .01). CONCLUSION: LN children with GMT had more severe clinical manifestations and renal pathologic damages, and poor outcome. Serum a-C1q level was positively correlated with a-ß2GP1, and a-ß2GP1 may be involved in the formation of GMT in children with LN, which might involve in the activation of complement classical pathway.

Clinical significance of kidney immune complex deposition in children with acute interstitial nephritis disease.

BACKGROUND: Acute interstitial nephritis (AIN) is a relatively rare cause of acute kidney injury (AKI) in children. Immune complex (IC) deposition was rare in renal pathology of AIN. METHODS: Based on the status and position of IC deposition, a total of 78 children with AIN were divided into two groups: the non-IC group and IC group. IC group was further divided into two subgroups: intraglomerular (IG)-IC group and extraglomerular (EG)-IC group. To compare the clinical and histological features, renal outcomes between groups. RESULTS: The IC deposition, IG-IC and EG-IC deposition were observed in 22 (28.21%), 12 (15.38%) and 10 (12.82%) children, respectively. The IC group demonstrated a higher frequency of AKI, higher level of Scr, urine N-acetyl-ß-D-glucosidase (NAG) enzyme, retinol-binding protein (RBP), neutrophil gelatinase-associated lipocalin (NGAL), higher frequency of neutrophils, plasma cells and eosinophils infiltrate, higher scores of interstitial inflammation (i), total inflammation (ti) and interstitial edema, lower level of estimated glomerular filtration rate (eGFR) as compared to non-IC group (p < 0.05, p < 0.01). EG-IC deposition positively moderate correlated with levels of RBP, IG-IC deposition positively moderate correlated with plasma cell infiltrate, interstitial inflammation (i), total inflammation (ti) and interstitial edema. Interstitial inflammation, EG-IC deposition and interstitial edema were risk factors for AKD in AIN, and interstitial fibrosis/tubular atrophy (IF/TA) was a risk factor for CKD in children with AIN. CONCLUSION: IG-IC and EG-IC deposition positively correlated with severe clinical manifestations, glomerular and tubular injuries, and EG-IC deposition was risk factor for the progression of AIN in children.

Comparative Functional Analysis in vitro of 2 COL4A5 Splicing Mutations at the Same Site in 2 Unrelated Alport Syndrome Chinese Families.

X-linked Alport syndrome (XLAS) is a common hereditary nephropathy caused by COL4A5 gene mutations. To date, many splice site mutations have been described but few have been functionally analyzed to verify the exact splicing effects that contribute to disease pathogenesis. Here, we accidentally discovered 2 COL4A5 gene splicing mutations affecting the same residue (c.2917+1G>A and c.2917+1G>C) in 2 unrelated Chinese families. In vitro minigene assays showed that the 2 mutations produced 3 transcripts in H293T cells: one with a 96-bp deletion in exon 33, one with exon 33 skipping, and one with exon 33-34 skipping. However, fragment analysis results showed that the main splicing effects of the 2 mutations were different, the c.2917+1G>A mutation mainly activated a cryptic donor splice site in exon 33 and resulted in the deletion of 96 bp in exon 33, while the c.2917+1G>C mutation mainly caused exon 33 skipping. Our findings indicate that different nucleotide substitutions at the same residue can cause different splicing effects, which may contribute to the variable phenotype of Alport syndrome.

Urinary proteomics of Henoch-Schönlein purpura nephritis in children using liquid chromatography-tandem mass spectrometry.

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) is the principal cause of morbidity and mortality in children with Henoch-Schönlein purpura (HSP). However, the criteria for risk assessment currently used is not satisfactory. The urine proteome may provide important clues to indicate the development of HSPN. METHODS: Here, we detected and compared the urine proteome of patients with HSPN and healthy controls by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the data-independent acquisition (DIA) mode. The differentially expressed proteins were analysed by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. For validation, enzyme-linked immunosorbent assay (ELISA) was used to analyse the selected proteins. RESULTS: A total of 125 proteins (29 upregulated and 96 downregulated) were found to be differentially expressed in children with HSPN compared with the controls. Forty-one proteins were predicted to have direct interactions. The enriched pathways mainly included focal adhesion, cell adhesion molecules, the PI3K-Akt signalling pathway, ECM-receptor interactions and so on. Cell adhesion related to the pathogenesis of HSPN was the main biological process identified in this study. The decrease in two proteins (integrin beta-1 and tenascin) was validated by ELISA. CONCLUSIONS: Our study provides new insights into the assessment of HSPN progression in children, as well as new potential biomarkers. The data confirm the value of the urinary proteome in capturing the emergence of HSPN.

Long non-coding RNA Snhg3 protects against hypoxia/ischemia-induced neonatal brain injury.

Hypoxic-ischemic brain damage (HIBD) is a major cause of morbidity and mortality in the preterm and term infant. However, the precise mechanism of HIBD remains largely elusive. As a newly discovered long non-coding RNA, small nucleolar RNA host gene 3 (Snhg3) has shown its important roles in cell apoptosis, proliferation, and disease development. In this study, we determined the role of Snhg3 in the pathogenesis of HIBD. Snhg3 expression was significantly down-regulated in the neonatal brain and primary hippocampal cells response to hypoxic/ischemic stress. Snhg3 overexpression protected against hypoxic/ischemic-induced brain injury in vivo and hippocampal cell injury in vitro. Snhg3 acted as the sponge of miR-196 in the hippocampal cells by regulating the expression of miR-196 target genes, XIAP and CAAP1. Moreover, Snhg3 overexpression decreased brain infarct size and ameliorated hypoxic-ischemic neonatal brain damage. This study suggests that Snhg3 is a potential target for the treatment of HIBD.

IPDN-China promotes the development of pediatric dialysis in China.

BACKGROUND: In mainland China, dialysis for children with end-stage renal disease (ESRD) was not introduced until the 1980s. To describe the development of pediatric dialysis in different regions of China, a national pediatric dialysis network, namely, International Pediatric Dialysis Network-China (IPDN-China) ( www.pedpd.org.cn ), was launched in 2012. METHODS: Original and updated information from the renal centers registered with the IPDN-China was collected between 2012 and 2016 from two sources, namely, the registry and the survey, and demographic features were analyzed. RESULTS: Due to promotion by the IPDN-China, the number of registered renal centers increased from 12 to 39 between 2012 and 2016, with a significant increase in the coverage of the Chinese administrative divisions (from 26.5 to 67.6%) (p < 0.01); and the coverage of the pediatric (0~14 years old) population increased to nearly 90% in 2016. The distribution of renal centers indicated that East China had the highest average number of registered centers per million population (pmp) 0~14-year-old age group. Seventeen relatively large dialysis centers were distributed across 14 divisions. Various modalities of renal replacement therapy (RRT) were available in most centers. The IPDN-China has promoted collaborations between dieticians, psychologists, and social workers on dialysis teams to provide better service to children with ESRD and their families. The proportion of centers with all three types of paramedic support (i.e., dieticians, psychologists, and social workers) as well as the proportion of centers with a partial paramedic team significantly increased between 2012 (25.0%) and 2016 (69.2%) (p < 0.05). In terms of the point prevalent cases of patients (aged < 18 years), data from the survey of 39 registered centers revealed that the number of children with ESRD who were on RRT was 578 (49% received a kidney transplant) at the end of 2016, which was more than that reported in previous surveys. Data from the registry showed that 349 dialysis patients had been enrolled as of the end of 2016. The median age at RRT start was 9.5 years, and the leading cause of ESRD was congenital abnormalities of the kidney and urinary tract (CAKUT). CONCLUSIONS: The IPDN-China has helped to promote the development of pediatric dialysis for ESRD in China by improving the organization of care for dialysis patients and increasing the availability and the quality of RRT for patients who need it. To improve knowledge about the epidemiology and outcomes of pediatric RRT around the country, a sustained effort needs to be made by the IPDN-China to increase the enrollment of dialysis patients and increase the number of registered centers in the future.

The correlation analysis between the Oxford classification of Chinese IgA nephropathy children and renal outcome - a retrospective cohort study.

BACKGROUND: The 2016 Oxford Classification's MEST-C scoring system predicts outcomes in adults with IgA nephropathy (IgAN), but it lacks tremendous cohort validation in children with IgAN in China. We sought to verify whether the Oxford classification could be used to predict the renal outcome of children with IgAN. METHODS: In this retrospective cohort study, 1243 Chinese IgAN children who underwent renal biopsy in Jinling Hospital were enregistered from 2000 to 2017. The combined endpoint was defined as either a ≥ 50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD). We probed into the relevance betwixt the Oxford classification and renal prognosis. RESULTS: There were 29% of children with mesangial proliferation(M1), 35% with endocapillary proliferation (E1), 37% with segmental sclerosis/adhesion lesion (S1), 23% with moderate tubular atrophy/interstitial fibrosis (T1 25-50% of cortical area involved), 4.3% with severe tubular atrophy/interstitial fibrosis (T2 > 50% of cortical area involved), 44% with crescent in< 25% of glomeruli(C1), and 4.6% with crescent in> 25% of glomeruli (C2). All children were followed for a medial of 7.2 (4.6-11.7) years, 171 children (14%) arrived at the combined endpoint. The multivariate COX regression model revealed that the presence of lesions S (HR2.7,95%CI 1.8 ~ 4.2, P<0.001) and T (HR6.6,95%CI 3.9 ~ 11.3, P<0.001) may be the reason for poorer prognosis in the whole cohort. In contrast, C lesion showed a significant association with the outcome only in children received no immunosuppressive treatment. CONCLUSIONS: This study revealed that S and T lesions were useful as the long-term renal prognostic factors among Chinese IgAN children.

GAS5 silencing protects against hypoxia/ischemia-induced neonatal brain injury.

Hypoxic/ischemic brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. However, the molecular mechanism of HIBD in the neonatal infant is still elusive. Long non-coding RNAs are shown as important regulators of brain development and many neurological diseases. Here, we determined the role of long noncoding RNA-GAS5 in HIBD. GAS5 expression was significantly up-regulated in hypoxic/ischemic-injured neonatal brain and hippocampal neurons. GAS5 silencing protected against hypoxic/ischemic-induced brain injury in vivo and primary hippocampal neuron injury in vitro. Mechanistically, GAS5 regulated hippocampal neuron function by sponging miR-23a. Intracerebroventricular injection of GAS5 shRNA significantly decreased brain GAS5 expression, reduced brain infarct size, and improved neurological function recovery. Collectively, this study suggests a promising therapeutic approach of GAS5 inhibition in the treatment of neonatal HIBD.

The COL4A3 and COL4A4 Digenic Mutations in cis Result in Benign Familial Hematuria in a Large Chinese Family.

Mutations in the COL4A5 gene result in X-linked Alport syndrome, homozygous or compound heterozygous mutations in COL4A3 or COL4A4 are responsible for autosomal recessive Alport syndrome, and heterozygous mutations in COL4A3 or COL4A4 cause autosomal dominant Alport syndrome or benign familial hematuria. Recently, the existence of a digenic inheritance in Alport syndrome has been demonstrated. We here report heterozygous COL4A3 and COL4A4 digenic mutations in cis responsible for benign familial hematuria. Using bioinformatics analyses and pedigree verification, we showed that COL4A4 c.1471C>T and COL4A3 c.3418 + 1G>T variants in cis are pathogenic and co-segregate with the benign familial hematuria. This result suggests that COL4A3 and COL4A4 digenic mutations in cis mimicking an autosomal dominant inheritance should be considered as a novel inheritance pattern of benign familial hematuria, although the disease-causing mechanism remains unknown.

Three Novel Heterozygous COL4A4 Mutations Result in Three Different Collagen Type IV Kidney Disease Phenotypes.

Thin basement membrane nephropathy (TBMN), autosomal dominant Alport syndrome (ADAS), and focal segmental glomerulosclerosis (FSGS) are kidney diseases that differ in clinical diagnosis, treatment, and prognosis. Nevertheless, they may result from the same causative genes. Here, we report 3 COL4A4 heterozygous mutations (p.Gly208Arg, p.Ser513Glufs*2, and p.Met1617Cysfs*39) that lead to 3 different collagen type IV kidney disease phenotypes, manifesting as TBMN, ADAS, and FSGS. Using bioinformatics analyses and pedigree verification, we show that these novel variants are pathogenetic and cosegregate with TBMN, ADAS, and FSGS. Furthermore, we found that the collagen type IV-associated kidney disease phenotypes are heterogeneous, with overlapping pathology and genetic mutations. We propose that COL4A4-associated TBMN, ADAS, and FSGS should be considered as collagen type IV kidney disease subtypes that represent different phases of disease progression.

Differentially expressed microRNAs in kidney biopsies from various subtypes of nephrotic children.

BACKGROUND: Our previous study showed a set of increased miRNAs in serum or urine from nephrotic syndrome children. In this study, we investigated the renal expression of these miRNAs in nephrotic children and explored their role in pathogenesis and as potential indicators to differentiate subtypes of kidney diseases. METHODS: We enrolled 52 children with six different subtypes of nephropathy, and 8 normal kidney tissues were used as controls. RT-qPCR was used to quantify the expression of miR-191, miR-151-3p, miR-150, miR-30a-5p and miR-19b in renal tissues. RESULTS: miR-191 and miR-151-3p exhibited significantly higher and lower intrarenal expression in all six subtypes of kidney diseases compared to controls. miR-19b was upregulated in three subtypes, and miR-30a-5p and miR-150 were downregulated in two and four subtypes, respectively. The intrarenal expression of miR-150 was significantly different between minimal change disease (MCD) and some other subtypes. The renal levels of these miRNAs correlated significantly with some renal functions and immune parameters. Bioinformatics showed that some target genes of these miRNAs were associated with immune and renal pathological changes. CONCLUSIONS: These five miRNAs may be involved in the pathogenesis of nephropathy in children. miR-150 is a potential typing indictor to differentiate MCD from other nephropathy subtypes.

Risk Factors and Clinical Outcomes of Renal Thrombotic Microangiopathy in Children with Lupus Nephritis in Terms of Pathological and Clinical Features.

BACKGROUND: Thrombotic microangiopathy (TMA) is an important risk factor for the prognosis of lupus nephritis (LN). Patients with LN complicated with TMA tend to be critically ill with high mortality and poor prognosis. In the present study, we retrospectively analyzed the clinical manifestations, laboratory results, renal pathological manifestations, and prognosis of children with LN-TMA and analyzed the risk factors for end-stage renal disease (ESRD) in children with LN-TMA. METHODS: Seventy-four patients with LN and renal TMA (rTMA) were selected and compared to 128 LN controls without TMA (1:2 ratio) matched according to demographics, pathological type and treatments. RESULTS: The mean values of systolic blood pressure, diastolic blood pressure (DBP), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), urinary protein quantitation (PRO), urine red blood cells, N-acetyl-ß-D-glucosidase (NAG), retinol-binding protein, systemic lupus erythematosus disease activity score (SLEDAI), and activity index (AI) scores in the TMA group were all higher than those in the non-TMA group (p < 0.05 and p < 0.01). The mean values of complement C3, hemoglobin, platelets, estimated glomerular filtration rate, and chronic index (CI) score in the TMA group were all lower than those in the non-TMA group (p < 0.05 and p < 0.01). The number of cases of glomerular crescent, fibrous crescent, endocapillary proliferation, tubular atrophy, interstitial fibrosis, C3 and C1q deposition in the TMA group was higher than that in the non-TMA group (p < 0.05 and p < 0.01). The 3-year and 5-year renal survival rates in the TMA group (88.93% vs. 97.00%, p < 0.05) and TMA group (61.41% vs. 82.31%, p < 0.05) were significantly lower than those in the non-TMA group. Multivariate Cox regression analysis showed that serum creatinine before treatment (≥110 µmol/L), TMA and interstitial fibrosis were independent risk factors for the development of ESRD in LN children. CONCLUSION: The general condition of children with TMA is critical, and the prognosis is poor. Early detection, early treatment and the development of new treatments are key to improving LN-TMA outcomes in children.

Clinical Characteristics of Children Infected with SARS-CoV-2 Omicron (B.1.1.529) in China's Shanghai.

Introduction: The pandemic of SARS-CoV-2 brings great challenge and threats to humans worldwide. Multiple variants of SARS-CoV-2 tend to be epidemic, among which Omicron is highly infectious within China. The aim of this study was to analyze the clinical characteristics of children infected with SARS-CoV-2 variant B.1.1.529 (Omicron) in the Shanghai, China. Methods: We included 9378 pediatric patients diagnosed with Omicron and treated in the Shanghai International Convention and Exhibition Center between April 1, 2022 and May 31, 2022. We recorded and summarized the clinical characteristics, infectious conditions and biological features of the children infected with Omicron. Results: A total of 9355 paediatric patients were treated in isolation since Makeshift became available, including 5564 males (59.48%) and 3791 females (40.52%). More than half (55.56%) of the affected children were identified at premises screening. The number of symptomatic or asymptomatic patients was 4530 (48.42%) and 4825 (51.58%), respectively. Initial signs or symptoms in asymptomatic patients included fatigue (3582, 38.29%), cough (560, 5.99%), fever (242, 2.59%) and other (146, 1.56%). Age and number of vaccinations in paediatric patients were negatively associated with the number of days from positive to negative nucleic acid test results. Conclusion: Age and number of vaccinations were key factors influencing the conversion of nucleic acid test results in paediatric patients. Early childhood vaccination is encouraged to establish a complete immune barrier.

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.

Increased serum and urinary microRNAs in children with idiopathic nephrotic syndrome.

BACKGROUND: MicroRNAs (miRNAs) are present in body fluids and may have the potential to serve as disease biomarkers. This study explored the clinical value of miRNAs in serum and urine as biomarkers for idiopathic childhood nephrotic syndrome (NS). METHODS: We obtained serum samples from 159 NS children (24 steroid resistant and 135 steroid sensitive), 109 age/sex-matched healthy controls and 44 children with other kidney diseases. Serum miRNAs were analyzed with the TaqMan Low Density Array and then validated with a quantitative reverse-transcription PCR assay with 126 individual samples. Moreover, we collected paired serum samples from 50 patients before and after treatment to determine the value of these miRNAs for condition assessment. In addition, urine samples from these patients were examined for candidate miRNAs. RESULTS: The concentrations of serum miR-30a-5p, miR-151-3p, miR-150, miR-191, and miR-19b were highly increased in NS children compared with controls (P < 0.0001). The urinary miR-30a-5p concentration was also increased in NS (P = 0.001). The area under the ROC curve and the odds ratio for the combined 5 serum miRNAs were 0.90 (95% CI, 0.86-0.94; P < 0.0001) and 40.7 (95% CI, 6.06-103; P < 0.0001), respectively. Moreover, the concentrations of the 5 serum miRNAs and urinary miR-30a-5p markedly declined with the clinical improvement of the patients. CONCLUSIONS: We determined that 5 distinct serum miRNAs and urinary miR-30a-5p were increased in NS children. These circulating or urinary miRNAs may represent potential diagnostic and prognostic biomarkers for idiopathic pediatric NS.

Serum microRNAs levels in primary focal segmental glomerulosclerosis.

BACKGROUND: MicroRNAs (miRNAs, miRs) are involved in most physiological, developmental, and pathological processes. miR-192 and miR-205 are expressed preferentially in the renal cortex and closely relevant to the renal cell biology. In the present study, we aim to measure the serum levels of miR-192 and miR-205 and their correlation with clinicopathological data in patients with primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). METHODS: Fifty-six patients (35 male, 21 female) with idiopathic nephrotic syndrome (FSGS 30, MCD 26) and 20 healthy controls were enrolled in the study. We quantified the serum levels of miR-192 and miR-205 in patients with FSGS and MCD by RT-qPCR. RESULTS: Patients with FSGS had higher serum levels of miR-192 and miR-205 than those with MCD (324.49 ± 42.74 fmol/l versus 90.19 ± 27.14 fmol/l, p < 0.01, 2.25 ± 0.69 fmol/l versus 0.60 ± 0.51 fmol/l, p < 0.01, respectively). The level of miR-192 was positively correlated with the proteinuria in patients with FSGS and MCD (r = 0.62, p < 0.001, r = 0.84, p < 0.001, respectively). Similarly, the level of miR-205 was positively correlated with the proteinuria in patients with FSGS (r = 0.54, p = 0.002). In addition, the serum level of miR-192 was significantly correlated with the degree of interstitial fibrosis in patients with FSGS (r = 0.342, p < 0.05). CONCLUSIONS: miR-192 and miR-205 have the potential as markers to differentiate FSGS from MCD.