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Abstract Aims The primary aim of this study was to characterize the health-related quality of life (HRQoL) and identify the associated factors among children aged 2 to 18 in China diagnosed with idiopathic nephrotic syndrome (INS). Additionally, the study aimed to evaluate the HRQoL and caregiving burden of their caregivers and investigate the correlation between the HRQoL of the children and that of their caregivers. Methods This study recruited 181 children diagnosed with INS from Children’s Hospital, Zhejiang University School of Medicine in China. The proxy-reported PedsQL Generic Core Module (PedsQL™ 4.0 GCM) was used to measure the HRQoL of children, and the EuroQol five-dimensional questionnaire, five-level version (EQ-5D-5L) was applied to measure caregivers’ HRQoL. Differences in scale scores and total scores of PedsQL™ 4.0 GCM were assessed using t-tests and one-way ANOVA. Multivariate linear regression analysis was used to identify the factors associated with children’s HRQoL. Pearson correlation analysis evaluated the correlation between children’s HRQoL and caregiver’s HRQoL. Results HRQoL of Children with INS declines with increasing age, and children aged 5-18 had lower scores in physical functioning, emotional functioning, school functioning, psychosocial health summary score, and total PedsQL™ 4.0 GCM score compared to healthy children. Various factors, including the mother filling out the questionnaire, the father being unemployed, and the use of other medications except for steroids, were associated with worse HRQoL of children (p values

Background: The treatment modalities for testicular appendage torsion in children are classified as conservative or surgical, and the choice is controversial. Objectives: This study aimed to identify ultrasound-based indicators influencing the outcome of conservative treatment in children with testicular appendage torsion to divide the boundaries between conservative and surgical management. Methods: A retrospective analysis was conducted on testicular appendage torsion data of children from November 2022 and November 2023 in the Children’s Hospital of Zhejiang University School of Medicine to compare the conservatively successful and conservatively unsuccessful groups’ clinical and ultrasound characteristics. Furthermore, we constructed a logistic regression model and evaluated its predictive ability. Results: We observed 405 (88.62%) and 52 (11.38%) cases of conservative success and failure, respectively. Univariate analysis indicated significant differences between these groups in testicular appendage torsion nodule size, terminology for hydrocele, scrotal wall edema, and increased epididymal blood flow (p

Dysregulated specificity proteins (SPs), members of the C2H2 zinc-finger family, are crucial transcription factors (TFs) with implications for renal physiology and diseases. This comprehensive review focuses on the role of SP family members, particularly SP1 and SP3, in renal physiology and pathology. A detailed analysis of their expression and cellular localization in the healthy human kidney is presented, highlighting their involvement in fatty acid metabolism, electrolyte regulation, and the synthesis of important molecules. The review also delves into the diverse roles of SPs in various renal diseases, including renal ischemia/reperfusion injury, diabetic nephropathy, renal interstitial fibrosis, and lupus nephritis, elucidating their molecular mechanisms and potential as therapeutic targets. The review further discusses pharmacological modulation of SPs and its implications for treatment. Our findings provide a comprehensive understanding of SPs in renal health and disease, offering new avenues for targeted therapeutic interventions and precision medicine in nephrology.

Background: Inherited kidney diseases (IKDs) in children pose unique diagnostic and therapeutic challenges. IKD significantly impact patient quality of life, morbidity, mortality, and cost to the healthcare system. With over 150 genetic abnormalities, they account for approximately 30% of cases requiring renal replacement therapy. There is an urgent need to advance both diagnosis and treatment strategies. In this review, we present recent advances in diagnosis and treatment for facilitating personalized treatment approaches. Summary: The diagnostic landscape for IKDs have evolved significantly, emphasizing precise genetic identification and classification of these disorders. Recent advancements include the refinement of genetic testing techniques, such as whole exome sequencing, which has improved the accuracy of diagnosing specific diseases and facilitated early intervention strategies. Additionally, this review categorizes IKDs based on genetic abnormalities and clinical manifestations, enhancing understanding and management approaches. Finally, it summarizes the corresponding treatment, and lists the application of emerging therapeutic options such as gene therapy and organoids, which show promise in transforming treatment outcomes. Key Messages: This review summarizes the common types of IKDs in children, including their diagnosis and treatment advances, and provides an update on the status of gene therapy development for these disorders.

Abstract Background Calcification is common in advanced atheromatous plaque, but its clinical significance remains unclear. This study aimed to assess the prevalence of plaque calcification in the moderate-to-severe internal carotid artery stenosis and investigate its relationship with ipsilateral ischemia. Methods The retrospective study included 178 patients detected with proximal internal carotid artery (pICA) stenosis of ≥ 50% on multidetector computed tomography at Zhejiang Hospital from January 2019 to March 2023. Association between plaque calcification characteristics (calcification thickness, position, type, circumferential extent, calcium volume and calcium score) and ipsilateral cerebrovascular events was analyzed. Results The 178 patients (mean age 71.24 ± 10.02 years, 79.78% males) had 224 stenosed pICAs overall. Plaque calcification was noted in 200/224 (89.29%) arteries. Calcification rates were higher in older age-groups. Calcification volume (r = 0.219, p

Background: Nephrotic syndrome is a special type of chronic kidney disease, the specific pathogenesis of which remains unclear. An increasing number of studies have suggested that B cells play an important role in the pathogenesis of nephrotic syndrome. Summary: Idiopathic nephrotic syndrome is a common kidney disease in children. While previously believed to be primarily caused by T-cell disorders, recent research has shifted its focus to B cells. Studies have shown that B cells play a significant role in the pathogenesis of NS, potentially even more so than T cells. This article provides a comprehensive review of the involvement of B cells in the development of idiopathic nephrotic syndrome. Key Messages: B cells are involved in the pathogenesis of nephrotic syndrome by producing autoantibodies and various cytokines.

The transient receptor potential canonical 6 (TRPC6) channel, a nonselective cation channel that allows the passage of Ca2+, plays an important role in renal diseases. TRPC6 is activated by Ca2+ influx, oxidative stress, and mechanical stress. Studies have shown that in addition to glomerular diseases, TRPC6 can contribute to renal tubular disorders, such as acute kidney injury, renal interstitial fibrosis, and renal cell carcinoma (RCC). However, the tubule-specific physiological functions of TRPC6 have not yet been elucidated. Its pathophysiological role in ischemia/reperfusion (I/R) injury is debatable. Thus, TRPC6 may have dual roles in I/R injury. TRPC6 induces renal fibrosis and immune cell infiltration in a unilateral ureteral obstruction (UUO) mouse model. Additionally, TRPC6 overexpression may modify G2 phase transition, thus altering the DNA damage checkpoint, which can cause genomic instability and RCC tumorigenesis and can control the proliferation of RCC cells. This review highlights the importance of TRPC6 in various conditions of the renal tubular system. To better understand certain renal disorders and ultimately identify new therapeutic targets to improve patient care, the pathophysiology of TRPC6 must be clarified.

Abstract. Over the past decade, mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney disease. However, the precise molecular mechanisms linking mitochondrial damage to kidney disease remain elusive. The recent insights into the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthetase (cGAS)-stimulator of interferon gene (STING) signaling pathway have revealed its involvement in many renal diseases. One of these findings is that mitochondrial DNA (mtDNA) induces inflammatory responses via the cGAS-STING pathway. Herein, we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage, focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney diseases. Furthermore, we summarize the latest findings of cGAS-STING signaling pathway in cell, with a particular emphasis on its downstream signaling related to kidney diseases. This review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway, kidney diseases, and mitochondrial dysfunction.

Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent hereditary disorder characterized by distinct phenotypic variability that has posed challenges for advancing in-depth research. Recent advancements in kidney organoid construction technologies have enabled researchers to simulate kidney development and create simplified in vitro experimental environments, allowing for more direct observation of how genetic mutations drive pathological phenotypes and disrupt physiological functions. Emerging technologies, such as microfluidic bioreactor culture systems and single-cell transcriptomics, have further supported the development of complex ADPKD organoids, offering robust models for exploring disease mechanisms and facilitating drug discovery. Nevertheless, significant challenges remain in constructing more accurate ADPKD disease models. This review will summarize recent advances in ADPKD organoid construction, focusing on the limitations of the current techniques and the critical issues that need to be addressed for future breakthroughs. New and Noteworthy: This review presents recent advancements in ADPKD organoid construction, particularly iPSC-derived models, offering new insights into disease mechanisms and drug discovery. It focuses on challenges such as limited vascularization and maturity, proposing potential solutions through emerging technologies. The ongoing optimization of ADPKD organoid models is expected to enhance understanding of the disease and drive breakthroughs in disease mechanisms and targeted therapy development.

This study aimed to discover novel serum biomarkers for IgA vasculitis with nephritis (IgAVN). The serum of IgA vasculitis (IgAV) patients without nephritis and IgAVN patients not treated with glucocorticoids was analyzed for 440 proteins using a novel quantitative planar protein microarray. To verify the biomarkers, semiquantitative immunofluorescence analysis was performed on selected differential cytokines in a separate cohort of kidney tissue samples. A total of 41 proteins were differentially expressed between the IgAVN and IgAV groups out of the 440 proteins analyzed. Five differentially abundant proteins, including VEGF R3, ADAM12, TIM-3, IL-12p40, and CEACAM-5, were further validated by semiquantitative immunofluorescence analysis in kidney tissue from independent cohorts. ADAM12, TIM-3, IL-12p40, and CEACAM-5 were expressed in kidney tissue. A linear relationship was observed between the pathological grade of IgAVN and the expression levels of ADAM12 and CEACAM-5. Furthermore, while the prognosis of children with IgAVN may have a linear relationship with CEACAM-5, the results did not indicate a significant statistical difference, which may be related to the sample size. The expression of ADAM12 and CEACAM-5 was positively correlated with the pathological grade. More importantly, we found that CEACAM-5 may be related to the prognosis of IgAVN, which could serve as a significant biomarker for assessing disease severity and monitoring disease progression.

Abstract Background This study aimed to identify an orcl1 mutation in a patient with Dent-2 Disease and investigate the underlying mechanisms. Methods The ocrl1 mutation was identified through exome sequencing. Knockdown of orcl1 and overexpression of the orcl1 mutant were performed in HK-2 and MPC5 cells to study its function, while flow cytometry measured reactive oxygen species (ROS), phosphatidylserine levels, and cell apoptosis. Scanning electron microscopy observed crystal adhesion, while transmission electron microscopy examined kidney tissue pathology. Laser scanning confocal microscopy was used to examine endocytosis, and immunohistochemical and immunofluorescence assays detected protein expression. Additionally, podocyte-specific orcl1 knockout mice were generated to investigate the role of orcl1 in vivo. Results We identified a mutation resulting in the replacement of Histidine with Arginine at position 318 (R318H) in ocrl1 in the proband. orcl1 was widely expressed in the kidney. In vitro experiments showed that knockdown of orcl1 and overexpression of ocrl1 mutant increased ROS, phosphatidylserine exocytosis, crystal adhesion, and cell apoptosis in HK-2 cells. Knockdown of orcl1 in podocytes reduced endocytosis and disrupted the cell cycle while increasing cell migration. In vivo studies in mice showed that conditional deletion of orcl1 in podocytes caused glomerular dysfunction, including proteinuria and fibrosis. Conclusion This study identified an R318H mutation in orcl1 in a patient with Dent-2 Disease. This mutation may contribute to renal injury by promoting ROS production and inducing cell apoptosis in tubular cells, while disrupting endocytosis and the cell cycle, and promoting cell migration of podocytes. Video Abstract

Abstract Background Steroid-resistant nephrotic syndrome (SRNS) is characterized by unrelieved proteinuria after an initial 4–8 weeks of glucocorticoid therapy. Genes in podocytes play an important role in causing SRNS. Objective This study aimed to report a pathogenic mutation in SRNS patients and investigate its effects on podocytes, as well as the pathogenic mechanism. Methods We screened out a novel mutation by using whole-exon sequencing in the SRNS cohort and verified it via Sanger sequencing. Conservative analysis and bioinformatic analysis were used to predict the pathogenicity of the mutation. In vitro, stable podocyte cell lines were constructed to detect the effect of the mutation on the function of the podocyte. Moreover, an in vivo mouse model of podocyte ANLN gene knockout (ANLN podKO) was used to confirm clinical manifestations. Transcriptome analysis was performed to identify differential gene expression and related signaling pathways. Results ANLN E841K was screened from three unrelated families. ANLN E841K occurred in the functional domain and was predicted to be harmful. The pathological type of A-II-1 renal biopsy was minimal change disease, and the expression of ANLN was decreased. Cells in the mutation group showed disordered cytoskeleton, faster cell migration, decreased adhesion, increased endocytosis, slower proliferation, increased apoptosis, and weakened interaction with CD2 association protein. ANLN podKO mice exhibited more obvious proteinuria, more severe mesangial proliferation, glomerular atrophy, foot process fusion, and increased tissue apoptosis levels than ANLN flox/flox mice after tail vein injection of adriamycin. Upregulated differentially expressed genes in cells of the mutation group were mainly enriched in the PI3K-AKT pathway. Conclusion The novel mutation known as ANLN E841K affected the function of the ANLN protein by activating the PI3K/AKT/mTOR/apoptosis pathway, thus resulting in structural and functional changes in podocytes. Our study indicated that ANLN played a vital role in maintaining the normal function of podocytes. Video Abstract

Background: Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are novel oral agents used for renal anemia treatment. Roxadustat, a first-in-class HIF-PHI used for treating anemia in chronic kidney disease patients, has been approved in China, Japan, South Korea, Chile, and Europe. Roxadustat is involved in HIF degradation, which can stimulate endogenous erythropoietin (EPO) production and improve iron utilization. Besides, roxadustat can promote dietary iron uptake and transport. In comparison with traditional erythropoiesis-stimulating agent treatment, it might reduce cardiovascular risk and mortality as it causes only a slight increase in the plasma EPO level. Phase II and III clinical trial reports have shown that roxadustat is effective for treating chronic kidney disease patients. The role of roxadustat in kidney transplant recipients (KTRs) needs to be examined as patients with chronic kidney disease are different from those receiving renal transplants. Summary: Clinical trials have demonstrated that roxadustat effectively increases and maintains hemoglobin levels in patients with dialysis-dependent and non-dialysis-dependent chronic kidney disease by stimulating endogenous EPO production and optimizing iron utilization. Roxadustat has recently been used effectively to treat patients with EPO-resistant anemia. It has also been used for treating patients with posttransplant anemia (PTA), which is a prognostic factor for mortality in KTRs with an iron deficiency and impaired glomerular filtration rate. Here, we examined the findings of four studies in a narrative review and discussed our perspectives regarding this field of study. Key Messages: Roxadustat significantly improves hemoglobin levels without affecting renal function in KTRs with PTA. It also enhances iron utilization by decreasing ferritin and hepcidin levels and increasing total iron binding capacity, transferrin, and serum iron levels. Roxadustat ameliorates anemia and inflammation, and might have reno-protective effects in KTRs.

Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by early-onset nephrotic syndrome and microcephaly with brain anomalies in children. Researchers studying GAMOS reported the first pathogenic variant identified was the WDR73 gene, and more recently, four new pathogenic genes, OSGEP, LAGE3, TP53RK, and TPRKB, have been identified. In the present study, we report a new mutation of c.290T>G (p.L97R) LAGE3 in a 4-year-old boy with specific urological and nephrological complications. The patient presented with early-onset proteinuria, brain atrophy, delayed language and motor development, and axial hypotonia. This patient also had mutations in two other genes: TRPC6 and NUP160, make the clinical presentation of this patient more diverse. Our novel findings add to the spectrum of pathogenic variants in the LAGE3 gene. In addition, early genetic diagnosis of GAMOS is essential for genetic counseling and prenatal care.

Abstract Background & aims Fabry disease (FD) is a rare X-linked metabolic storage disorder due to the deficiency of lysosomal α-galactosidase A which causes the accumulation of glycosphingolipids throughout the body. Underweight and low BMI have been occasionally reported in FD patients previously. Whether underweight is common in the early stage of FD and body composition analysis to determine the cause have not been reported. Methods Children who were diagnosed with FD in the Children’s Hospital of Zhejiang University School of Medicine from July 2014 to December 2022 were enrolled. Clinical data were obtained from medical records. Whole body dual energy X-ray absorptiometry scans (DXA) were used to assess body composition (fat mass, FM; fat free mass, FFM and bone mass) according to the International Society of Clinical Densitometry’s standard operating method. Whole body muscle mass was calculated as fat-free mass minus bone mass. Appendicular skeletal muscle mass (ASM) was calculated as the sum of the arm and the leg muscle mass. The FM, FFM, ULSM and LLSM indices were calculated by dividing the total FM, FFM, and upper and lower limb skeletal muscle mass (ULSM and LLSM) by the height squared. Results A total of eighteen children (14 boys and 4 girls) were enrolled. Thirteen boys had the classical phenotype, and five children (1 boy with the N215S mutation and 4 girls) had the late-onset phenotype. Seven children with the classical phenotype (53.8%) and two of the five children (40%) with the late-onset phenotype had abnormal BMIs. Sixteen of the eighteen children (88.9%) had a height in the normal range, suggesting that low BMI was mainly due to underweight. By DXA body composition analysis, the FMI was abnormal in 3 children (2 boys and 1 girl), and the FFMI was abnormal in 12 children (9 boys and 3 girls). For the classical phenotype, 2 of the 13 children (15.4%) had abnormal FMI values, while 10 (76.9%) had abnormal FFMI values. Eight patients (61.5%) with the classical phenotype had a significant reduction in muscle mass index, ASM index and LLSM index values compared with age- and sex- matched Chinese controls. Late-onset patients also had mild low skeletal muscle mass compared to controls. The results suggested that low skeletal muscle mass is common in early FD. Conclusions This is the first study to examine body composition and muscle mass in early Fabry disease patients. Low skeletal muscle mass is a common early symptom in children with Fabry disease, suggesting that skeletal muscle is significantly affected in the early stages of FD.

Abstract Integrins are heterodimeric receptors comprising α and β subunits. They are expressed on the cell surface and play key roles in cell adhesion, migration, and growth. Several types of integrins are expressed on the platelets, including αvβ3, αIIbβ3, α2β1, α5β1, and α6β1. Among these, physically αIIbβ3 is exclusively expressed on the platelet surface and their precursor cells, megakaryocytes. αIIbβ3 adopts at least three conformations: i) bent-closed, ii) extended-closed, and iii) extended–open. The transition from conformation i) to iii) occurs when αIIbβ3 is activated by stimulants. Conformation iii) possesses a high ligand affinity, which triggers integrin clustering and platelet aggregation. Platelets are indispensable for maintaining vascular system integrity and preventing bleeding. However, excessive platelet activation can result in myocardial infarction (MI) and stroke. Therefore, finding a novel strategy to stop bleeding without accelerating the risk of thrombosis is important. Regulation of αIIbβ3 activation is vital for this strategy. There are a large number of molecules that facilitate or inhibit αIIbβ3 activation. The interference of these molecules can accurately control the balance between hemostasis and thrombosis. This review describes the structure and signal transduction of αIIbβ3, summarizes the molecules that directly or indirectly affect integrin αIIbβ3 activation, and discusses some novel antiαIIbβ3 drugs. This will advance our understanding of the activation of αIIbβ3 and its essential role in platelet function and tumor development.

As a sign of chronic kidney disease (CKD) progression, renal fibrosis is an irreversible and alarming pathological change. The accurate diagnosis of renal fibrosis depends on the widely used renal biopsy, but this diagnostic modality is invasive and can easily lead to sampling error. With the development of imaging techniques, an increasing number of noninvasive imaging techniques, such as multipara meter magnetic resonance imaging (MRI) and ultrasound elastography, have gained attention in assessing kidney fibrosis. Depending on their ability to detect changes in tissue stiffness and diffusion of water molecules, ultrasound elastography and some MRI techniques can indirectly assess the degree of fibrosis. The worsening of renal tissue oxygenation and perfusion measured by blood oxygenation level-dependent MRI and arterial spin labeling MRI separately is also an indirect reflection of renal fibrosis. Objective and quantitative indices of fibrosis may be available in the future by using novel techniques, such as photoacoustic imaging and fluorescence microscopy. However, these imaging techniques are susceptible to interference or may not be convenient. Due to the lack of sufficient specificity and sensitivity, these imaging techniques are neither widely accepted nor proposed by clinicians. These obstructions must be overcome by conducting technology research and more prospective studies. In this review, we emphasize the recent advancement of these noninvasive imaging techniques and provide clinicians a continuously updated perspective on the assessment of kidney fibrosis.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by the development of fluid-filled cysts in the kidneys. The primary cause of ADPKD is mutations in the PKD1 (polycystic kidney disease 1) or PKD2 (polycystic kidney disease 2) gene. Patients with ADPKD often develop a variety of vascular abnormalities, which have a major impact on the structure and function of the blood vessels and can lead to complications such as hypertension, intracranial aneurysm (ICAN), and atherosclerosis. The progression of ADPKD involves intricate molecular and cellular processes that lead to the development of these vascular abnormalities. Our understanding of these processes remains incomplete, and available treatment options are limited. The aim of this review is to delve into the underlying mechanisms of these vascular abnormalities and to explore potential interventions.

The research and application of immune checkpoint inhibitors (ICIs) have enormously promoted the progression of tumor treatment. Gradual implementation of ICIs in clinical practice is largely limited as they exert uncontrolled collateral effects on the immune system, such as immune-related adverse events (irAEs); this includes rarely reported glomerular diseases. This study aimed to describe the clinical and pathological manifestation of ICIs-induced glomerular diseases and focused on the mechanism and therapeutic strategy for glomerular diseases associated with ICIs. The data of 53 patients with glomerular diseases related to ICIs were retrieved from the PubMed database. The most frequently reported ICIs-related glomerular diseases were pauci-immune glomerulonephritis (28.3%), podocytopathies (26.4%), and immune-complex glomerulonephritis (18.9%). Moreover, anti-PD1 antibodies were the most commonly used ICIs (71.4%). Most patients receiving ICIs discontinued the treatment (89.4%) and were initiated with steroids (87.2%). Rituximab was also useful in the treatment, especially for renal vasculitis. Rechallenging ICIs could be considered for cancer progression or as salvage therapy, where rechallenging ICI therapy with steroids may be beneficial. We believe the treatment should be personalized based on the degree of renal pathology, serum creatinine (Scr), and tumor progression to obtain a good prognosis.

Summary: Nephronophthisis-like nephropathy-1 (NPHPL1) is a rare ciliopathy, caused by mutations of XPNPEP3. Despite a well-described monogenic etiology, the pathogenesis of XPNPEP3 associated with mitochondrial and ciliary function remains elusive. Here, we identified novel compound heterozygous mutations in NPHPL1 patients with renal lesion only or with extra bone cysts together. Patient-derived lymphoblasts carrying c.634G>A and c.761G>T together exhibit elevated mitochondrial XPNPEP3 levels via the reduction of mRNA degradation, leading to mitochondrial dysfunction in both urine tubular epithelial cells and lymphoblasts from patient. Mitochondrial XPNPEP3 was co-immunoprecipitated with respiratory chain complex I and was required for the stability and activity of complex I. Deletion of Xpnpep3 in mice resulted in lower activity of complex I, elongated primary cilium, and predisposition to tubular dilation and fibrosis under stress. Our findings provide valuable insights into the mitochondrial functions involved in the pathogenesis of NPHP.

Abstract Background Multiple magnetic foreign body ingestion in children is increasingly common and can cause serious injury. The present study aimed to analyze the clinical features of such cases and summarize treatment experiences. Methods A retrospective survey of 91 patients in the Children’s Hospital, Zhejiang University School of Medicine with magnetic foreign body ingestion from October 2018 to October 2021 was performed, the data were collected including the clinical information of the patients, treatment details, and prognosis. Results Twenty-two (24.2%) patients were conservatively treated, with the foreign bodies discharged through the anus, 31 (34.1%) underwent laparoscopic surgery, including 18 cases converting from laparoscopic surgery to laparotomy, and 38 (41.8%) underwent laparotomy. In 13 (14.3%) patients, the foreign bodies were partially removed by gastroscope. The remaining foreign bodies were removed by laparoscopy in six patients, including three cases converting from laparoscopy to laparotomy, by laparotomy in four patients, and by conservative treatment in three patients. Conclusions Multiple magnetic foreign body ingestion can cause significant harm to patients and different clinical techniques must be used for patients in different situations to reduce the harm to children.

Abstract Background Early and accurate identification of infection viruses among children can benefit the personalized medical treatment and management, and reduce the future occurrence of serious symptoms. Thus, it is critical to develop a high-throughput multiplex real-time RT-PCR method to improve the accuracy and efficiency in routine clinical lab tests. Methods We developed a real time RT-PCR combined with melting curve analysis (RRCMC) method for simultaneous detection of rotavirus A, B, C, norovirus GI and GII, adenovirus, astrovirus and sapovirus. Results Stool samples were collected from 160 children with acute diarrhea and tested by RRCMC assay. A total of 71 patients were tested positive with norovirus, adenovirus or rotavirus. The RRCMC assay has high specificity. There is no internal cross-reaction among the 8 diarrhea viruses and no cross-reaction of other commonly intestinal pathogens and human genome. The limit detection was ranged from 1 × 102 to 1 × 105 nucleic acid copies/ml for each diarrhea virus. Conclusion The RRCMC method is a suitable rapid clinical test for infectious viruses, with the advantages of high-throughput, low cost, high sensitivity and specificity.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder. Renal involvement in FD is characterized by proteinuria and progressive renal decline. Reports on FD with nephrogenic diabetes insipidus as the initial manifestation are rare. In this paper, we report a pediatric case with an N215S variant. Results: A boy with an onset of polydipsia and polyuria at approximately 4 years of age was diagnosed with nephrogenic diabetes insipidus. Whole-exome sequencing showed a GLA N215S variation with no secondary cause of diabetes insipidus. No family history of polydipsia or polyuria was reported; however, the patient's maternal grandmother and her two younger brothers had hypertrophic cardiomyopathy. Both brothers required surgery due to severe cardiac involvement, and the youngest brother died of heart disease at the age of 50 years. The patient's polydipsia and polyuria worsened over the next 7 years. Serum sodium was normal, but the patient required high-dose potassium chloride to maintain normal serum potassium levels. His physical and intellectual development was normal, with no common complications of nephrogenic diabetes insipidus, such as anemia, malnutrition, vomiting, high fever, or convulsions. Dried blood spot testing showed α-galactosidase A (α-gal A) activity of 0.6 μmol/L/h and a Lyso-GL-3 level of 7.01 ng/ml. The patient developed mild proteinuria and mild myocardial hypertrophy. Renal biopsy showed myeloid bodies and zebra bodies. After more than 1 year of ERT, his urine specific gravity increased to 1.005–1.008, which was a new sign reflecting the efficacy of ERT, although urine output was maintained at 3–5 ml/kg/hour. We will continue to monitor the patient's renal tubular function and urine output. Conclusions: Nephrogenic diabetes insipidus may be the initial manifestation in children with FD and/or N215S variation. In FD, the same mutation in a family may present a completely different phenotype.

Anemia is a common complication of chronic kidney disease (CKD), and its prevalence rises as the disease progresses. Intravenous or subcutaneous erythropoiesis-stimulating agents (ESAs) are advised to treat CKD-associated anemia, since shortage of erythropoietin (EPO) and iron are the main cause of anemia. However, ESA resistance and safety have spurred a lot of interest in the development of alternate anemia therapies. Roxadustat, an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that increases erythropoiesis and may modulate iron metabolism, was recently licensed in China, Chile, South Korea, Japan and the European Union for the treatment of CKD-related anemia. Despite this, clinical trials have shown a number of adverse effects, including cardiovascular disease, hyperkalemia, and infections. In addition, of concern is roxadustat's possible effects on other organs and systems. In this review, based on clinical evidence, we discuss the potentially detrimental effects of roxadustat to the known biology on systems other than kidney, and the need for long-term follow-up in order for roxadustat to be approved in more countries in the future.

Stress granules (SGs) are distinct RNA granules induced by various stresses, which are evolutionarily conserved across species. In general, SGs act as a conservative and essential self-protection mechanism during stress responses. Viruses have a long evolutionary history and viral infections can trigger a series of cellular stress responses, which may interact with SG formation. Targeting SGs is believed as one of the critical and conservative measures for viruses to tackle the inhibition of host cells. In this systematic review, we have summarized the role of SGs in viral infection and categorized their relationships into three tables, with a particular focus on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Moreover, we have outlined several kinds of drugs targeting SGs according to different pathways, most of which are potentially effective against SARS-CoV-2. We believe this review would offer a new view for the researchers and clinicians to attempt to develop more efficacious treatments for virus infection, particularly for the treatment of SARS-CoV-2 infection.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive genetic disorder caused by mutations in the AGXT gene. The hepatic peroxisomal enzyme alanine glyoxylate aminotransferase (AGT) defects encoded by the AGXT gene increase oxalate production, resulting in nephrocalcinosis, nephrolithiasis, chronic kidney disease, and kidney failure. Traditional pharmacological treatments for PH1 are limited. At present, the treatment direction of PH1 is mainly targeted therapy which refer to a method that targeting the liver to block the pathway of the production of oxalate. Lumasiran (OxlumoTM, developed by Alnylam Pharmaceuticals), an investigational RNA interference (RNAi) therapeutic agent, is the first drug approved for the treatment of PH1, which was officially approved by the US Food and Drug Administration and the European Union in November 2020. It is also the only drug that has been shown to decrease harmful oxalate. Currently, there are 5 keys completed and ongoing clinical trials of lumasiran in PH1. Through the three phase III trials that completed the primary analysis period, lumasiran has been shown to be effective in reducing oxalate levels in urine and plasma in different age groups, such as children, adults, and patients with advanced kidney disease, including those on hemodialysis. In addition to clinical trials, cases of lumasiran treatment for PH1 have been reported in small infants, twin infants, and children diagnosed with PH1 after kidney transplantation. These reports confirm the effectiveness and safety of lumasiran. All adverse events were of mild to moderate severity, with the most common being mild, transient injection-site reactions. No deaths or severe adverse events were reported. This article reviews PH1 and lumasiran which is the only approved therapeutic drug, and provide new options and hope for the treatment of PH1.

BackgroundIn the absence of effective measures to predict steroid responsiveness, patients with nonhereditary steroid-resistant nephrotic syndrome (SRNS) have a significantly increased risk of progression to end-stage renal disease. In view of the poor outcomes of SRNS, it is urgent to identify the steroid responsiveness of idiopathic nephrotic syndrome (INS) early.MethodsTo build a prediction model for SRNS, we collected 91 subjects; 57 of them had steroid-sensitive nephrotic syndrome, and the others had SRNS. For each subject, 87 clinical variables were measured. In general, only a small part of these variables is informative to SRNS. Thus, we proposed a new variable selection framework including a penalized regression approach (named MLR+TLP) to select variables having a linear effect on the SRNS and a nonparametric screening method (MAC) to select variables having a nonlinear marginal (joint) effect on the SRNS. Thereafter, considering the correlation between selected clinical variables, we used a stepwise method to build our final model for predicting SRNS. In addition, a statistical testing procedure is proposed to test the overfitting of the proposed model.ResultsTwenty-six clinical variables were selected to be informative to SRNS, and an SVM model was built to predict SRNS with a leave-one-out cross-validation (LOO-CV) accuracy of 95.2% (overfitting p value

Background: The kidney requires abundant blood supply, and oxygen is transmitted by diffusion through blood vessels. Most physiological metabolism of the kidney depends on oxygen, so it is very sensitive to oxygen. An increasing pool of evidence suggests that hypoxia is involved in almost all acute and chronic kidney diseases (CKDs). Vascular damage, tubular injury, and fibrosis are the main pathologies associated during hypoxia. Hypoxia-inducible factors (HIFs) are the main mediators during hypoxia, but their functions remain controversial. This article reviewed recent studies and described its mechanisms on renoprotection. Summary: HIF is degraded rapidly during under normal oxygen. But under hypoxia, HIFs accumulate and many target genes are regulated by HIFs. Homeostasis during injury is maintained through these genes. Pretreatment of HIF can protect the kidney from acute hypoxia and can improve repair, but HIF’s role in CKD and in renal tumor is still controversial. Due to its mechanism in kidney disease, many drugs toward HIFs are widely researched, even some of which have been used in clinical or in clinical research. Key Messages: In this review, we described the known physiological mechanisms, target genes, and renal protective roles of HIFs, and we discussed several drugs that are researched due to such renal protective roles.

Abstract Background Pathogenic variants of PAX2 cause autosomal-dominant PAX2-related disorder, which includes variable phenotypes ranging from renal coloboma syndrome (RCS), congenital anomalies of the kidney and urinary tract (CAKUT) to nephrosis. Phenotypic variability makes it difficult to define the phenotypic spectrum associated with genotype. Methods We collected the phenotypes in patients enrolled in the China national multicenter registry who were diagnosed with pathogenic variant in PAX2 and reviewed all published cases with PAX2-related disorders. We conducted a phenotype-based cluster analysis by variant types and molecular modeling of the structural impact of missense variants. Results Twenty different PAX2 pathogenic variants were identified in 32 individuals (27 families) with a diagnosis of RCS (9), CAKUT (11) and nephrosis (12) from the Chinese cohort. Individuals with abnormal kidney structure (RCS or CAKUT group) tended to have likely/presumed gene disruptive (LGD) variants (Fisher test, p

BackgroundHutchinson–Gilford Progeria Syndrome (HGPS) is a ultrarare, fatal autosomal dominant disorder. The pathogenesis of the disease is a mutation in LMNA, which leads to the accumulation of progerin in cells, impairing the normal physiological functions. Stroke and transient ischemic attack seriously affect the survival rate and quality of life of HGPS children, although the literature of this aspect is limited. This study summarizes the clinical manifestations and related imaging features of HGPS children with stroke to improve pediatric clinicians' understanding of this disease.Case presentationBoth children have a de novo heterozygous mutation of LMNA [c.1824C > T ( p.G608G)]. Case 1. At the age of 4 years, the child had a cerebral infarction, which manifested as blurred vision and communication disturbance. Multiple abnormal signals were observed on the head MRI in the bilateral frontoparietal cortex, bilateral semiovale center, lateral ventricle, and deep frontal and parietal lobes. Multiple abnormal white matter signals on head MRA: bilateral internal carotid artery stenosis with basilar artery, and bilateral thickening of the posterior communicating artery. Case 2. At the age of 8.5 years, the child presented with cerebral infarction, which manifested as decreased muscle strength and choking after drinking water. MRI of the head showed that the bilateral frontal lobes were small with multiple abnormal signal shadows in the bilateral center of the semiovale and the lateral ventricle. Brain MRA revealed that the bilateral internal carotid arteries (C5–7) were narrow and uneven in thickness, and the A1 segment of the left anterior cerebral artery was narrower than the contralateral one. After symptomatic and supportive treatment, the two children improved.ConclusionHemiplegia and physical weakness are the most prevalent stroke symptoms in children with HGPS, followed by headache, epilepsy, dysarthria, and psychosis as the primary manifestation in some children. Stroke in children with HGPS is mostly ischemic cerebral infarction caused by an insufficient cerebral blood supply. Pediatric cerebral infarction mainly occurs in the large vascular area, involving all vascular areas, with the internal carotid artery and middle cerebral artery being the most commonly accumulated.

BackgroundMinimal change disease (MCD) has a high recurrence rate, but currently, no biomarker can predict its recurrence. To this end, this study aimed at identifying potential serum cytokines as valuable biomarkers for predicting the risk of MCD recurrence.Materials and methodsRaybiotech 440 cytokine antibody microarray was used to detect the serum samples of eight relapsed, eight non-relapsed MCD patients after glucocorticoid treatment, and eight healthy controls. The differentially expressed cytokines were confirmed by enzyme-linked immunosorbent assay (ELISA) with serum samples from 29 non-relapsed and 35 relapsed MCD patients. The study used the receiver operating characteristic (ROC) curve analysis to investigate the sensitivity and specificity of a serum biomarker for predicting the MCD relapse.ResultsSerum IL-12p40 levels increased significantly in the relapsed group. The Area Under the ROC Curve (AUC) of IL-12p40 was 0.727 (95%CI: 0.597–0.856; P < 0.01). The RNA-sequencing analysis and qPCR assay performed on the IL-12 treated mouse podocytes and the control group showed increased expression of podocyte damage genes, such as connective tissue growth factor (CTGF), matrix metallopeptidase 9 (MMP9), secreted phosphoprotein 1 (SPP1), and cyclooxygenase-2 (COX-2) in the former group.ConclusionIL-12p40 may serve as a new biomarker for predicting the risk of MCD recurrence after glucocorticoid treatment, and it may be involved in the pathogenesis and recurrence of MCD.

A specific emitter identification method based on deep residual network (DRN) is proposed to solve the problem that the traditional expert features relying on artificial extraction are difficult to characterize the subtle differences of specific emitters.The DRN is used to complete the identification task. The in-phase component (I-way) and the quadrature component (Q-way) of signal sample data are inputted into the DRN for training. The performance of the proposed method is evaluated by experiments on datasets containing actual collected ADS-B signals from different planes. The results show that the proposed DRN model achieves high classification accuracy without manual feature selection. Furthermore, data augmentation on signal-to-noise ratio can further improve the performance of the model.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, accounting for approximately 5% of all ESRD cases worldwide. As a vasopressin receptor 2 antagonist, tolvaptan is the FDA-approved therapeutic agent for ADPKD, which is only made available to a limited number of adult patients; however, its efficacy in pediatric patients has not been reported widely. Summary: Tolvaptan was shown to delay ADPKD progression in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 study, Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trial, and other clinical studies. In addition to its effects on aquaretic adverse events and alanine aminotransferase elevation, the effect of tolvaptan on ADPKD is clear, sustained, and cumulative. While ADPKD is a progressive disease, the early intervention has been shown to be important and beneficial in hypotheses as well as in trials. The use of tolvaptan in pediatric ADPKD involves the following challenges: patient assessment, quality of life assessment, cost-effectiveness, safety, and tolerability. The ongoing, phase 3b, 2-part study (ClinicalTrials.gov identifier: NCT02964273) on the evaluation of tolvaptan in pediatric ADPKD (patients aged 12–17 years) may help obtain some insights. Key Messages: This review focuses on the rationality of tolvaptan use in pediatric patients with ADPKD, the associated challenges, and the suggested therapeutic approaches.

Abstract Demethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers’ expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.

Abstract Existing research suggests that the human immune system and immune cells are involved in the pathogenesis of nephrotic syndrome, but there is still a lack of direct evidence. This study tried to analyze the profiling of immune cells in the peripheral blood of steroid-sensitive nephrotic syndrome (SSNS) patients and steroid-resistant nephrotic syndrome (SRNS) patients before and after standard steroid treatment to clarify the immunological mechanism of nephrotic syndrome patients. The number and proportion of CD4 + T cells in patients with nephrotic syndrome remained unchanged. However, there is an imbalance of Th1 and Th2 and an excessive increase of Th17 cells. The number of CD8 + T cells and the number of effector CD8 + T cells in them increased significantly, but only in SSNS, the number of activated CD8 + T cells increased, and the number of activated Treg cells decreased significantly. Nephrotic syndrome patients also have B cell disorder, and it is more prominent in SSNS patients. Compared with the normal control, only the number of B cells and plasmablast in SSNS patients increased significantly (Z = − 2.20, P = 0.028). This study also observed that transitional B cells decreased in both SSNS and SRNS patients, but SSNS patients' decrease was lower than in SRNS patients. Compared with normal controls, monocytes in patients with nephrotic syndrome decreased significantly. The main reason was that Non-classical Monocyte decreased, while Classical Monocyte increased slightly. The total number of NK cells did not change, but the internal cell subgroups' composition occurred. Changes, realized as CD56hi NK cells increased, CD56low NK cells decreased; and the above trend is more evident in SSNS patients. Patients with nephrotic syndrome have immune disorders, including T cells, B cells, Monocytes, and NK cells. It can be confirmed that immune factors are involved in the pathogenesis of the nephrotic syndrome.

Summary: The current procedure thoroughly explains how to reprogram induced pluripotent stem cells (iPSCs) from the patient’s peripheral blood mononuclear cells (PBMCs), a less invasive source; e.g., somatic cells. We describe how to isolate PBMCs and reprogram them into iPSCs by electroporation. Furthermore, we provide an alternative approach to generating iPSC using Geltrex or Matrigel matrix to replace MEF-feeder. The challenge of this process is the relatively lower cell survival rates of PBMCs due to the damage of electroporation.For complete details on the use and execution of this protocol, please refer to Hu et al. (2021). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Increasing genetic and biochemical evidence has broadened our view of the pathomechanisms that lead to Spinal muscular atrophy (SMA) and Amyotrophic lateral sclerosis (ALS), two fatal neurodegenerative diseases with similar symptoms and causes. Stress granules are dynamic cytosolic storage hubs for mRNAs in response to stress exposures, that are evolutionarily conserved cytoplasmic RNA granules in somatic cells. A lot of previous studies have shown that the impaired stress granules are crucial events in SMA/ALS pathogenesis. In this review, we described the key stress granules related RNA binding proteins (SMN, TDP-43, and FUS) involved in SMA/ALS, summarized the reported mutations in these RNA binding proteins involved in SMA/ALS pathogenesis, and discussed the mechanisms through which stress granules dynamics participate in the diseases. Meanwhile, we described the applications and limitation of current therapies targeting SMA/ALS. We futher proposed the promising targets on stress granules in the future therapeutic interventions of SMA/ALS.

Membranous nephropathy (MN) falls within the scope of a glomerular disease. MN exhibits subepithelial immune- complex deposition and capillary wall thickening which could occur in all age groups. In comparison with adult patients with MN, MN in pediatric population has a lower incidence and more secondary factors (e.g., systemic lupus erythematosus, infection, malignancy, or drug toxicity). Two target antigens for the immune complexes, PLA2R (identified in 2009) and THSD7A (in 2014), found in previous studies and first presented in adult MN, are found in pediatric patients suffering from MN and their antibodies are now an effective tool for diagnosis and monitoring in children and adolescents. Several novel antigens have been identified (e.g., EXT1/EXT2, NELL1, Sema3B, PCDH7, HTRA1, and NCAM1) over the past few years. Each of them represents different clinical and pathologic findings. In-depth research should be conducted to gain insights into the outcomes and pathophysiology of the above novel antigen-associated MN. Targeted treatment opinions for different novel antigen-related MN are under development both in adults and pediatric patients.

Patients with epidermolysis bullosa (EB) could develop significant urological complications, such as hydroureteronephrosis, renal amyloidosis and IgA nephropathy (IgAN). Here, we presented a 12-year-old boy carrying pathogenic COL7A1 mutation with diagnosis of dystrophic epidermolysis bullosa (DEB). The patient had concomitant gross hematuria and proteinuria. Pathological examinations and immunostaining of renal biopsy showed glomeruli with mesangial hypercellularity and deposition of IgA, which were indicative of IgAN. Interestingly, serological evaluation showed antineutrophil cytoplasmic antibody (ANCA) directed against myeloperoxidase and proteinase 3. Treatment with glucocorticoid, immunosuppressants, angiotensin-converting enzyme inhibitor and antibiotics efficiently improved hemato-proteinuria, and ANCAs became negative as well. This case of DEB presented a unique collection of clinical manifestations and pathological alterations. IgAN and serum positive ANCA were possibly associated with sustained infection secondary to DEB, and can be managed by empirical treatment for primary IgAN.

Abstract Background Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disorder. Up to now, reports on the clinical characteristics of MPS IVA mainly focused on patients with progressive bone dysplasia and multiple organ damage, while the effects of this disorder on neurogenic bladder have not been reported. Therefore, the aim of the present study is to report two cases of nocturnal enuresis finally diagnosed as neurogenic bladder in MPS IVA. Case presentation Both children were characterized by the presence of pectus carinatum, kyphoscoliosis, nocturnal enuresis, urinary incontinence, normal intelligence, and loss of strength in the legs, diagnosed as neurogenic bladder in association with MPS IVA through the analysis of the clinical characteristics, enzyme activity and genetic testing. In addition, the terminator codon mutation c.1567T > G (p.X523E) and a novel missense mutation c.575A > G (p.E192G) were found in the coding region of the GALNS gene of the 1st patient, while the missense mutation c.488C > A (p.P163H) was found in the coding region of the GALNS gene of the 2nd patient. Conclusions Neurogenic bladder may occur in patients with MPS IVA after spinal cord injury. It is necessary to screen for the diagnosis of MPS IVA in patients with atypical enuresis and skeletal abnormalities through the analysis of the clinical characteristics, enzyme activity and genetic testing.

Abstract People with cardiovascular disease (CVD) often contract coronavirus disease 2019 (COVID‐19). However, the interaction between COVID‐19 and CVD is unclear. In this systematic review, the available evidence for the crosstalk between COVID‐19 and CVD and its treatment was analysed. A search was performed in the electronic databases MEDLINE and EMBASE. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infects human cells via angiotensin‐converting enzyme 2. SARS‐CoV‐2 can cause CVD by inducing cytokine storms, creating an imbalance in the oxygen supply and demand and disrupting the renin–angiotensin–aldosterone system; SARS‐CoV‐2 infection can also lead to the development of CVD through the side effects of therapeutic drugs, psychological factors, and aggravation of underlying CVD. The most common CVDs caused by SARS‐CoV‐2 infection are acute myocardial injury, arrhythmia, and heart failure. Studies have found that there is an interaction between COVID‐19 and CVD. Underlying CVD is associated with a high risk of mortality in patients with COVID‐19. SARS‐CoV‐2 infection can also cause new‐onset CVD. Clinicians need to pay close attention to cardiovascular complications during the diagnosis and treatment of patients with COVID‐19 to reduce patient mortality.

Abstract Background 13q33–q34 microdeletions are rare chromosomal aberrations associated with a high risk of developmental disability, facial dysmorphism, cardiac defects and other malformation of organs. It is necessary to collect and report evidence of this rare chromosome mutation to improve the prognosis of this rare disease. Case presentation We report a patient harboring an 11.56 Mb microdeletion at 13q33.1–34 region, which contains about 30 OMIM genes. Besides the common clinical manifestations such as facial dysmorphism, developmental delay, intellectual disability, epilepsy, and congenital heart disease, she also suffered from a reduced anogenital distance, hematuria and left renal hypoplasia. Most related cases were characterized by facial deformity and heart defects, but there were few reports on renal malformation, especially regarding renal hypoplasia with hematuria. Conclusion We have reported a patient suffering from a reduced anogenital distance, hematuria and left renal hypoplasia. A de novo 11.56 Mb deletion ranging from 13q33.1 to 13q34 (Chr13:103542220–115,106,996) was found by SNP-array analysis. It might be the first time for hematuria and renal hypoplasia to be reported as symptoms of 13q33-q34 deletion syndrome Neurodevelopmental disability, heart defects and urogenital/anorectal anomalies may be resulted from common or overlapping regions of deletion in chromosome bands 13q33.1-q34 and may share a common molecular mechanism.

Abstract Background Female Dent disease 1 patients with low-molecular-weight proteinuria (LMWP) due to CLCN5 gene mutation were rarely reported, and these cases that the people were also with Turner syndrome (TS) were even hardly documented before. Case presentation Here we report a 3-year and 11-month old Chinese girl with short stature who had a karyotype of 46,X,i(X)(q10) and a de novo pathogenic variant in the CLCN5 gene on the short arm of X chromosome. Laboratory examinations showed that the patient had LMWP, hypercalciuria, hypophosphatemia, delayed bone age, and genital dysplasia. Conclusion The combination of i(X)(q10) and CLCN5 mutation causes the deletion of the wild-type CLCN5 allele that results in Dent-1 and TS. To the best of our knowledge, this is the first case that a female CLCN5 mutation hemizygote is diagnosed with Dent-1 and Turner syndrome due to isochromosome X. Also, our case has indicated that the prevalence of the situation may be largely underestimated because of the mild signs of females with Dent-1.