Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of pediatric kidney failure, but predicting individual progression remains challenging. This multicenter study developed and validated POCC, a machine learning model for predicting kidney failure risk at 1, 3, and 5 years post-diagnosis in CAKUT patients. Two versions were created using data from 2249 children. The general model achieved internal AUCs of 0.93-0.99 and external AUCs of 0.89-0.98 and 0.81-0.90 in two independent validations at pediatric and general hospitals, respectively. The specialized model, integrating congenital-hereditary features, achieved internal AUCs of 0.93-0.99 and external AUCs of 0.91-0.96 in pediatric hospitals. Deployed online, POCC demonstrated 90.7% accuracy in real-world validation. As the first tool for multi-timepoint risk prediction across diverse CAKUT subphenotypes per patient, POCC has strong potential to support personalized management.

Vesicoureteral reflux (VUR) can cause retrograde urine flow under voiding pressure, facilitating ascending bacterial colonisation and recurrent inflammatory responses. These processes trigger a cascade of cellular and molecular events-innate immune activation, pro-inflammatory cytokine release, oxidative stress, apoptosis and extracellular matrix deposition-thereby promoting tubulointerstitial remodelling and increasing the risk of renal parenchymal injury and scarring. Static renal 99mTc-DMSA scintigraphy primarily reflects tracer uptake by proximal tubular cells in the renal cortex and can serve as an integrated phenotypic readout of tubular dysfunction and focal cortical involvement. However, its clinical interpretation remains experience-dependent and lacks reproducible quantitative criteria, while voiding cystourethrography (VCUG), the diagnostic and grading gold standard for VUR, is limited by invasiveness and procedural burden. In this study, we collected DMSA data from 346 children with febrile urinary tract infection treated at the Second Affiliated Hospital of Wenzhou Medical University between January 2019 and January 2023 and developed a deep learning model (MedSwinNet) for VUR risk stratification. Built on a Swin Transformer backbone and enhanced with multi-scale representation fusion, a convolutional block attention module and a gated selection strategy, MedSwinNet was designed to sensitively capture phenotypic signals such as reduced proximal tubular uptake and focal cortical defects while improving robustness. On the test set, the model achieved accuracies of 0.8290 under the severe-side input setting and 0.7997 under the bilateral-side input setting, demonstrating stable discriminative performance and favourable generalisation. Quality control analyses indicated broadly consistent distributions of key image quality metrics across data splits, mitigating potential bias from dataset shift. Collectively, deep learning-based decoding of tubular dysfunction-related phenotypic readouts enables noninvasive quantification of VUR-associated renal involvement, supports decision-making on whether VCUG is warranted and may reduce unnecessary invasive procedures while improving clinical risk-stratified management.

PURPOSE:Nephrotic syndrome (NS) is the main cause of the increasing end-stage renal disease (ESRD) patients worldwide. Podocytes are considered the crucial cells involved in the progression of NS, and their damage can directly lead to proteinuria. The objective of this study was to explore the protective effects of xanthohumol (XN) on podocyte injury. METHODS:Adriamycin (ADR)-induced podocyte injury in vivo and in vitro models were established to explore the effects of XN on adriamycin nephropathy (AN) by urine and serum biochemical assay, periodic acid-schiff (PAS) staining, immunohistochemistry, immunofluorescence, western blot, and real-time quantitative PCR (RT-qPCR). RESULTS:The results showed that XN could upregulate the expressions of podocyte specific marker Wilms' tumor protein 1 (Wt1), and glomerular filtration related functional proteins such as Nephrin, Synaptopodin, Zonula occludens 1 (ZO-1), and Crumbs2 (Crb2) as well as downregulate the expression of podocyte injury marker Desmin in ADR-treated podocytes to restrain the podocyte actin cytoskeleton disruption. CONCLUSION:Our study showed that XN treatment significantly attenuated ADR-induced podocyte injury, suggesting that XN may be a potential therapy option for patients with NS.

Exosomes derived from tumors are critical agents in intercellular communication and the tumor microenvironment, offering a rich source of signatures for renal cell carcinoma (RCC) diagnosis. Conventional diagnostic techniques often suffer from limited sensitivity and can be invasive. This study presents an innovative approach using near-infrared (NIR) digital PCR (dPCR) with black phosphorus-embedded gelatin microcarriers for profiling exosomal miRNAs and modulating STAT3 signaling and macrophage polarization. Microcarriers produced via microfluidics, characterized by their phase-change and photothermal properties, are subjected to thermal cycling using a custom NIR source. The study identified a 4.2-fold increase in miR-210 levels in RCC cells (ACHN and A498) compared to normal cells (HK-2), with miR-126 and miR-30c levels decreasing by 7-9 times. Additionally, the method achieved a 20-fold enrichment of miRNA-34 in exosomes, leading to reduced STAT3 expression and decreased M2 macrophage polarization after co-incubation. This pioneering dPCR method provides a robust tool for early RCC detection through exosomal miRNA profiling and opens new avenues for therapeutic exosome engineering. The study underscores the potential of dPCR-based exosome genotyping in identifying cancer biomarkers and developing novel treatment strategies.

Primary nephrotic syndrome (PNS) is a prevalent kidney disorder in pediatric patients, characterized by significant proteinuria, hypoalbuminemia, and edema, which poses serious health risks and economic burdens due to frequent relapses and hospitalizations. This study aims to explore the utility of shear wave elastography (SWE) as a novel, non-invasive biomarker for assessing renal health in this population. We used a cross-sectional design involving 76 pediatric patients with PNS and a control group, and measured renal stiffness through SWE The clinical characteristics of the nephrotic group were collected, including age, sex, disease duration, clinical type, 24-h urine protein, plasma albumin, and the relationship with 2D-SWE value was analyzed. Our results demonstrated a significant difference in renal elasticity, with the nephrotic syndrome group exhibiting a mean shear wave velocity (YM) of 22.36 ± 8.53 kPa compared to 17.51 ± 4.09 kPa in controls (p < 0.05). Furthermore, the area under the ROC curve for SWE was 0.67, indicating moderate predictive capability for renal damage. Notably, there were no significant differences in YM values across various clinical classifications of nephrotic syndrome, suggesting a uniform renal damage assessment irrespective of clinical type. Additionally, renal elasticity did not significantly vary regardless of whether the patient’s proteinuria had improved. (p = 0.464), indicating SWE’s potential as an independent biomarker. Our findings highlight the promise of SWE in enhancing diagnostic accuracy and prognostic evaluation in pediatric nephrotic syndrome. Shear wave elastography is a valuable noninvasive method for assessing renal elasticity in children with primary nephrotic syndrome.

Objective This study aims to elucidate the genetic and phenotypic characteristics of pediatric patients with potential Dent disease (DD).Methods High-throughput sequencing was conducted on 11 pediatric patients with potential cases of DD. We also analyzed clinical phenotype and treatment regimens.Result Variants in CLCN5 and OCRL were identified in nine patients, including three novel variants. The predominant clinical manifestations among these patients with a definitive diagnosis of DD included low molecular weight proteinuria (LMWP) (100%), hypercalciuria (66.7%), abnormal renal function (55.6%), nephrocalcinosis (44.4%), and hypophosphatemia (44.4%). Patients with CLCN5 or OCRL variants exhibited significantly elevated levels of both β2-microglobulin and α1-microglobulin, exceeding the normal threshold by more than tenfold. In contrast, the potential cases of DD without identified genetic mutations showed a moderate increase in β2-microglobulin (5-10 times the normal level), while α1-microglobulin levels remained below this range. Seven DD patients were treated with nonsteroidal angiotensin-converting enzyme inhibitors. By the end of this study, five DD patients were diagnosed with stage 2 chronic kidney disease (CKD2), while four were classified as having CKD1.Conclusion This study provides insight into the clinical and genetic profiles of DD patients. Notably, integrating genetic analysis with the detection of markedly elevated levels of LMWP, particularly α1-microglobulin,can substantially reduce the misdiagnosis of this disease.

Background: Variants in the COL4A4 gene have been identified as a significant cause of autosomal Alport syndrome. This study aimed to investigate the genetic features, clinical manifestations, and genotype-phenotype correlations in Chinese children with COL4A4 variants. Methods: 19 children with COL4A4 variants who presented with hematuria and/or proteinuria as their main complaints were included in our analysis. Genetic variants were identified using next-generation sequencing, Sanger sequencing and comprehensive bioinformatics analysis. Clinical data and family histories were retrospectively collected. Results: A total of 17 distinct COL4A4 variants were identified, 10 of which had not been previously described (10/17). Among these novel variants, 3 were likely pathogenic variants (3/10) and 1 was pathogenic variant (1/10). Among 19 patients, two carried compound heterozygous variants, one was homozygous, and the remainder were heterozygous. Most children presented with hematuria (4 had gross hematuria and 15 microscopic) and had a family history of kidney disease, with no extrarenal manifestations. In our cohort, frameshift, and missense COL4A4 variants were related to varying degrees of Alport kidney disease and nonsense variants resulted in isolated hematuria. Conclusion: This is the first study to apply the new classification of Alport kidney disease to Chinese pediatric patients with COL4A4 variants, substantially expanding the spectrum of COL4A4 variants and providing new insights into genotype-phenotype correlations in this population.

Acute pancreatitis (AP) is a prevalent, destructive, non-infectious pancreatic inflammatory disease, which is usually accompanied with systemic manifestations and poor prognosis. Gastrodin (4-hydroxybenzyl alcohol 4-O-β-d-glucopyranoside) has ideal anti-inflammatory effects in various inflammatory diseases. However, its potential effects on AP had not been studied. In this study, serum biochemistry, H&E staining, immunohistochemistry, immunofluorescence, western blot, real-time quantitative PCR (RT-qPCR) were performed to investigate the effects of Gastrodin on caerulein-induced AP pancreatic acinar injury model in vivo and lipopolysaccharide (LPS) induced M1 phenotype macrophage model in vitro. Our results showed that Gastrodin treatment could significantly reduce the levels of serum amylase and serum lipase while improving pancreatic pathological morphology. Additionally, it decreased secretion of inflammatory cytokines and chemokines, and inhibited the levels of p-p38/p38, p-IκB/IκB as well as p-NF-κB p-p65/NF-κB p65. Overall our findings suggested that Gastrodin might be a promising therapeutic option for patients with AP by attenuating inflammation through inhibition of the p38/NF-κB pathway mediated macrophage cascade.

Background: Type 1 diabetes mellitus (T1DM) is one of the most common endocrine and metabolic diseases in children. Pancreatic β cells are thought to be critical cells involved in the progression of T1DM, and their injury would directly lead to impaired insulin secretion. Purpose: To investigate the protective effects of allicin on pancreatic β cell injury and elucidate the underlying mechanism. Methods: The streptozotocin (STZ)-induced mouse T1DM model in vivo and STZ-induced pancreatic β cell Min6 model in vitro were used to explore the effects of allicin on T1DM. The experiments include fasting blood glucose test, oral glucose tolerance detection, HE staining, immunohistochemistry, immunofluorescence, TUNEL staining, western blot, real-time quantitative PCR (RT-qPCR), and flow cytometry. Results: Allicin could significantly decrease blood glucose level, improve islet structure and insulin expression, and inhibit apoptosis to reduce STZ-induced pancreatic β cell injury and loss through activating AMPK/mTOR mediated autophagy pathway. Conclusion: Allicin treatment significantly reduced STZ-induced T1DM progression, suggesting that allicin may be a potential therapy option for T1DM patients.

Background: Nephrotic syndrome (NS) is a chronic kidney disease mainly caused by impaired podocytes, ultimately resulting in massive proteinuria or even end-stage renal disease (ESRD). Methods: The objective of this study was to explore the potential pathogenesis of NS caused by podocyte injury, and further explore the underlying mechanism through data mining, bioinformatics analysis, and experimental verification. The integrated analyses including Seurat, CellChat, gene ontology (GO), and molecular docking were performed based on the single-cell RNA-seq data (scRNA-seq). The adriamycin (ADR)-induced podocyte injury model in vitro was established to conduct the experimental verification for bioinformatics analysis results through western blot and real-time quantitative PCR (RT-qPCR). Results: The results of bioinformatics analysis revealed that the bone morphogenetic protein (BMP) signaling pathway was involved in the podocyte-to-podocyte communication, which plays a crucial role in podocyte injury. The expression of BMP7 was significantly increased in ADR-induced podocytes through activating the Adenosine-monophosphate activated-protein kinase/Mammalian target of rapamycin (AMPK/mTOR) mediated autophagy pathway, and these findings were confirmed by in vitro experiments. Conclusion: This study first demonstrated that BMP7 participated in ADR-induced podocyte injury. The BMP7/ AMPK/mTOR mediated autophagy pathway may play a crucial role in podocyte injury, which may be the potential therapeutic target for NS patients.

School urinary screening programming can be useful for the early detection of renal and urinary disorders. However, urine screening is not included in the school health check-up in our region. Therefore, from February 2012 to March 2021, 12,497 school students were screened for urinalysis, and a long-term follow-up took place via an electronic medical record system. Among these screened students, 719 (5.75%) positive individuals received a repeat urinalysis 2 weeks later. During the 9-year medical record system follow-up period, 5 children had renal biopsies and 2 children had a diagnosis of IgA nephropathy (IgAN), while the remaining 3 children were diagnosed with thin basement membrane disease (TBM), primary nephrotic syndrome (PNS), and were suspected of C3 glomerulopathy, respectively. By this, calling for the school urine screening program as a physical examination item for primary and secondary school-aged students will contribute to enabling early detection of urine abnormalities and allow for early treatment.

目的 探讨使用婴幼儿局部皮肤刺激排尿的方法协助留取尿液标本的效果.方法 选取2019年3月至2020年2月尿路感染需留取尿标本的患儿266例,随机分为对照组和观察组,对照组按常规方法宣教指导留取尿液标本;观察组使用婴幼儿局部刺激排尿的方法协助排尿并留取尿液标本,比较两组留尿成功时间,入院后首次抗生素使用时间,中段尿标本污染情况,年龄分层后留尿成功率、主要照顾家属焦虑程度等指标.结果 观察组2?h内留尿成功率、中段尿标本合格率高于对照组(P<0.05).不同月龄比较,小月龄患儿使用刺激排尿的方法效果更好;观察组入院后首次抗生素执行时间、家属焦虑评分测定均优于对照组,差异有统计学意义(P<0.05).结论 婴幼儿局部皮肤刺激的方法能有效诱导患儿排尿、准确及时留取尿标本,一定程度提高标本合格率,减少家长的焦虑心情.

目的:研究地塞米松(Dex)对水通道蛋白2(AQP2)的体外直接调控效应,明确该作用是否依赖于PKA信号通路.方法:制备AQP2野生型及突变型质粒,突变型质粒通过突变AQP2 C末端4个PKA磷酸化位点(S256、S261、S264和S269)阻断PKA信号通路.AQP2野生型及突变型质粒分别转染HEK293细胞和显微注射爪蟾卵母细胞,再予共转染PKA质粒或Dex 0.1 μmol/L干预,采用蛋白质印迹(Western blot)法检测AQP2总蛋白表达,通过细胞表面生物素化评估AQP2膜蛋白表达,比较各组爪蟾卵母细胞的水渗透性差别.结果:Dex及PKA均显著上调HEK293细胞的AQP2膜蛋白及总蛋白表达(均P＜0.01);与野生型相比,PKA磷酸化位点的突变显著抑制了体外PKA直接诱导的AQP2磷酸化;突变后AQP2的膜蛋白及总蛋白表达均显著下调(均P＜0.01);PKA磷酸化位点突变后,Dex及PKA对AQP2膜蛋白及总蛋白表达的上调效应均被显著抑制(均P＜0.01);Dex及PKA均显著增加爪蟾卵母细胞水通透活性,PKA磷酸化位点突变后,该效应被显著抑制(均P＜0.01).结论:Dex对AQP2的总蛋白及膜蛋白表达具有显著的上调效应,该作用依赖于PKA信号通路实现.

Gitelman Syndrome (GS) is an inherited autosome recessive disorder syndrome, which can be caused by the gene mutations of solute carrier family 12 member 3 gene (SLC12A3). In present study, the urine cells (UCs) of a 7-year-old male GS patient with the homozygote SLC12A3 gene mutation p.T60M (c.179C > T) were reprogrammed into induced pluripotent stem cells (iPSCs) named WMUi021-A through the commercial Sendai virus reprogramming kit. The pluripotent markers OCT4 and SOX2 can be expressed positively in WMUi021-A, which can be differentiated into three germ layers in vitro as well as maintain a stable karyotype (46, XY).

Antley-Bixler syndrome (ABS) is a rare inherited autosome recessive malformation syndrome, which can be caused by the gene mutations of cytochrome P450 oxidoreductase (POR). In this study, the urine cells (UCs) derived from a 5-year-old female ABS patient with the homozygote POR gene mutation p.R457H (c.1825C>G) were reprogramming into induced pluripotent stem cells (iPSCs) named WMUi018-A using a commercial Sendai virus reprogramming kit. The pluripotent markers of stem cells like OCT4 and SOX2 can be positively expressed in this iPSC line, which can be induced to differentiate into three germ layers in vitro and maintain a stable karyotype (46, XX).

Bartter Syndrome (BS) is a group of rare inherited autosome-recessive disease, which can be caused by the gene mutations of sodium–potassium-chloride cotransporter gene (SLC12A1). Here, the urine cells (UCs) derived from a 4-year-old female BS patient with the homozygote SLC12A1 gene mutation p.A244D (c.731C>A) were reprogramming into induced pluripotent stem cells (iPSCs) named WMUi019-A using a commercial Sendai virus reprogramming kit. The pluripotent stem cell markers like OCT4 and SSEA4 can be positively expressed in this iPSC line, which can also be induced to differentiate into three germ layers in vitro and maintain a stable karyotype (46, XY).

The gene mutations of the chloride channel gene (CLCN5) can lead to the inherited X-linked Dent disease (X-Dent). The urine cells of a 4-year-old male X-Dent patient with the hemizygous CLCN5 gene mutation p.R718* (c.2152C > T) were reprogrammed into induced pluripotent stem cells (iPSCs) using integration free Sendai virus reprogramming system. The generated iPSCs stably expressed pluripotent stem cell markers and can be induced to differentiate into three germ layers in vitro. The karyotype of the generated iPSCs was normal (46, XY).

Lowe Syndrome (LS) is a rare X-linked multisystemic disorder syndrome, which can be caused by the gene mutations of OCRL. In present study, the urine cells (UCs) derived from a 12-year-old male LS patient with the hemizygote OCRL gene mutation p.M876N (c.2626dupA) were reprogrammed into induced pluripotent stem cells (iPSCs) named WMUi031-A through the commercial Sendai virus reprogramming kit. The pluripotent markers OCT4 and SOX2 can be expressed positively in WMUi031-A, which can be differentiated into three germ layers in vitro as well as maintain a stable karyotype (46, XY).

OBJECTIVE To study the clinical features of vesicoureteral reflux (VUR) in children with neurogenic bladder (NB), and to provide a reference for its early diagnosis and treatment. METHODS Clinical data were collected from 26 children with NB and urinary tract infection who were admitted to the Department of Pediatric Nephrology from January 2014 to December 2019. According to the presence or absence of VUR, the children were divided into a VUR group with 11 children and a non-VUR group with 15 children. Clinical features were compared between the two groups. RESULTS Compared with the non-VUR group, the VUR group had a significantly higher proportion of children with non-Escherichia coli urinary tract infection, hydronephrosis (the severity of hydronephrosis increased with the grade of VUR), abnormal 99mTc-DMSA renal scanning findings, elevated ratios of urinary albumin, urinary IgG and urinary transferrin to creatinine, increased residual urine volume, and increased detrusor leak point pressure (P < 0.05). CONCLUSIONS When NB children have the clinical manifestations of non-Escherichia coli urinary tract infection, hydronephrosis, abnormal 99mTc-DMSA renal scanning findings, glomerular proteinuria, increased bladder residual urine volume, and high detrusor leak point pressure, such children may already have VUR, and so diagnosis and intervention should be performed as early as possible.

The mutations of polyglutamine binding protein 1 gene (PQBP1) can lead to the rare inherited X-linked Renpenning syndrome (X-RSY). Here, an induced pluripotent stem cell (iPSC) line WMUi017-A was generated through reprogramming the urine cells of a 5-year-old male X-RSY patient with the hemizygous PQBP1 gene mutation p.P609A (c.1825C>G) using the commercial Sendai virus reprogramming system. The established iPSCs can stably express pluripotent stem cell markers OCT4 and NANOG, and can be induced into three germ layers and maintain a normal karyotype (46, XY) in vitro.