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To construct a therapeutic play program for children undergoing preparation for kidney biopsy under local anesthesia and explore the feasibility of the program from stakeholders' perspectives.The program was constructed by a multidisciplinary team and the feasibility and acceptability of the program were explored by a descriptive qualitative study.Based on LazarusFolkman's stress-coping model and Piaget's theory of play, and using on-site participatory field observation, a multidisciplinary team constructed a therapeutic play program for children undergoing kidney biopsy under local anesthesia. The feasibility and acceptability of the program were evaluated by interviewing children, their caregivers, and physicians.The main tools constructed for the intervention were a 15-page picture book titled Kidney Biopsy Treasure Hunt and a homemade kidney biopsy play package. The therapeutic play intervention for kidney biopsy under local anesthesia was led by nurses and followed the steps of kidney biopsy, using the picture book, and group play simulation. Through informed in-depth interviews with 10 children and their caregivers, we showed that the therapeutic play program materials were accessible, clinically feasible, and necessary for kidney biopsy under local anesthesia in children. The children and their caregivers had high acceptance of the content of the picture book, the format of the play, and high satisfaction with the overall program.The therapeutic play program we constructed for children undergoing kidney biopsy with local anesthesia was simple, feasible, and well accepted in the clinical setting.

To describe the home care experience, challenges and coping strategies of caregivers with children on automatic peritoneal dialysis (PD) in mainland China during the early stage of the COVID-19 outbreak.A qualitative descriptive approach was adopted. Semi-structured telephone interviews were conducted among 14 families with children on automatic peritoneal dialysis from February 2nd to 10th, 2020. The care routine, stress and coping strategies of caregivers of children on peritoneal dialysis were collected. The data were analysed using thematic analysis.Four key themes were defined: (1) concerns about PD treatment intertwined with worries about COVID-19; (2) retaining a sense of normality in the middle of the challenges; (3) staying safe; and (4) staying positive and carrying on.Families with children on automatic PD addressed the stress from COVID-19 and its containment measures by closely adhering to COVID-19 preventative measures, actively adjusting mentality and maintaining a sense of normality during the outbreak. This implies that healthcare staff need to be more aware of the complex medical needs of families with children on automatic PD, advocate for them and facilitate their navigation through the repurposed healthcare system.

BACKGROUND: To investigate the risk factors for breakthrough urinary tract infection (BT-UTI) in children with vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). METHODS: This was a single-centre cohort study (January 2016 to December 2019). The clinical data of 256 children with grade I–V VUR receiving CAP were analysed. In this study, exposure variables were sex, younger age at the initial diagnosis of UTI ≤12 months, high-grade VUR, bilateral VUR, aetiology, presence of renal scarring at the initial diagnosis, presence of renal function impairment at the initial diagnosis, ultrasound abnormalities, antibiotic used and bladder and bowel dysfunction (BBD). Outcome was BT-UTI. RESULTS: BT-UTI occurred in 81 out of 256 children with grade I–V VUR who received CAP, an incidence of 31.64%. Univariate analysis showed that younger age at the initial diagnosis of UTI (≤12 months), bilateral VUR, renal scarring on the dimercaptosuccinic acid (DMSA) scan at the initial diagnosis of UTI and BBD were correlated with the occurrence of BT-UTI. Multivariate analysis showed that younger age at the initial diagnosis of UTI (≤12 months) [hazard ratio (HR): 4.629; 95% confidence interval (CI): 1.302–16.462], bilateral VUR (HR: 2.078; 95% CI: 1.084–4.022) and BBD (HR: 3.194; 95% CI: 1.243–8.206) were independent risk factors for the occurrence of BT-UTI. CONCLUSIONS: For VUR children receiving CAP, younger age at the initial diagnosis of UTI (≤12 months), bilateral VUR, and BBD were independent risk factors for the occurrence of BT-UTI.

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is a rare histopathologic pattern of glomerular injury with limited studies in pediatric patients. Characteristics and outcomes of children with MPGN have also remained to be further explored. METHODS: We retrospectively reviewed the clinicopathological features, genetic findings, treatments and outcomes in 17 pediatric patients pathologically diagnosed with MPGN from 2007 to 2020 in the Children’s National Medical Center in China. RESULTS: Median age at disease onset was 9.9 years (IQR, 5.6–11.9 years). Most of the patients (12/17) had nephrotic range of proteinuria, and nephritic-nephrotic syndrome was the most common clinical presentation (35.2%). Secondary causes were identified in eight patients including hepatitis B virus (HBV) infection (n=4), methylmalonic acidemia (MMA, n=2), rheumatoid arthritis (RA, n=1) and Aymé-Gripp Syndrome (n=1). The nine patients with primary MPGN were further identified as immune-complex mediated MPGN (n=8), and unclassifiable MPGN (U-MGPN, n=1). Genetic analyses identified pathogenic variants of MMACHC gene in two cases of MMA and established the diagnosis for Aymé-Gripp syndrome in one case with a de novo variant of MAF gene. Comparing study between the complete or partial remission group (n=8) and non-response group (n=9) showed a significant difference in the timing of renal biopsy (P

BackgroundArtificial intelligence (AI)-assisted diagnosis is considered to be the future direction of improving the efficiency and accuracy of pediatric diseases diagnosis, while the existing research based on AI are far from sufficient because of limited data amount, inadequate coverage of disease types, or high construction costs, and have not been applied on a large scale. We aimed to develop an accurate deep learning model trained on millions of real-world data to verify the feasibility of the technology, and build the whole process of outpatient auxiliary diagnosis.Methods and findingsWe applied a Chinese Natural Language Processing (NLP) and an end-to-end deep neural network classifier to the outpatient’s electronic medical records (EMRs) in a single child care center in Shanghai, China, to unstructured text processing and construct an auxiliary diagnostic model, all patients were aged from 0 to 18 years. A training cohort with millions of records and an independent validation cohort with tens of thousands of records were intake separately and calculate diagnosis concordance rate (DCR) of model in each diseases group. The records with inconsistent diagnoses between human and AI were evaluated by clinical experts’ group, and calculate the relative correct rate (RCR) to evaluate the diagnostic performance of the model. A total of 5,271,347 medical records were intake in model training covering sixteen categories of diseases according to disease coding, reaching a DCR of 95· 49% (95· 48∼95· 51). For validation, 91,880 records were obtained from validation dataset, which reached a DCR of 93· 51% (93· 35∼93· 67) and FDCR of 72.04% (71· 75∼72· 33). It was confirmed that the accuracy of the model was still higher than that of human with most RCR>1 in validation dataset.ConclusionsThe deep learning system could support diagnosis of pediatric diseases, which has high diagnostic performance, comprehensive disease coverage, feasible technology, and can be promoted in multiple sites in the future.FundingThe Authors received no specific funding for this work.

Impaired type I interferons (IFNs) may cause immune deficiency in tumours. Current supplementary IFN therapy partially restores anticancer immunity but simultaneously induces immune evasion by upregulating multiple immune checkpoints. Here we create a T lymphocyte membrane-decorated epigenetic nanoinducer that is engineered with programmed cell death protein 1 (PD1), which we call OPEN, for the delivery of the IFN inducer ORY-1001. OPEN increases IFNs and blocks IFN-induced immune checkpoint upregulation. OPEN also targets tumours that express programmed cell death ligand 1 (PDL1) through PDL1/PD1 recognition and subsequently triggers the internalization of OPEN and immune checkpoint proteins. OPEN, which is loaded with ORY-1001, upregulates intratumoural IFNs and downstream major histocompatibility complex I and PDL1. The replenished PDL1 enables further ligation of OPEN, which in turn blocks PDL1. These sequential processes result in an eight- and 29-fold increase of the intratumoural densities of total and active cytotoxic T lymphocytes, respectively, and a strong inhibition of xenograft tumour growth. This T lymphocyte membrane-decorated epigenetic nanoinducer presents a generalizable platform to boost antitumour immunity.

Kidney disease is manifested in a wide variety of phenotypes, many of which have an important hereditary component. To delineate the genotypic and phenotypic spectrum of pediatric nephropathy, a multicenter registration system is being implemented based on the Chinese Children Genetic Kidney Disease Database (CCGKDD). In this study, all the patients with kidney and urological diseases were recruited from 2014 to 2020. Genetic analysis was conducted using exome sequencing for families with multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early-onset or extrarenal features. The genetic diagnosis was confirmed in 883 of 2256 (39.1%) patients from 23 provinces in China. Phenotypic profiles showed that the primary diagnosis included steroid-resistant nephrotic syndrome (SRNS, 23.5%), glomerulonephritis (GN, 32.2%), congenital anomalies of the kidney and urinary tract (CAKUT, 21.2%), cystic renal disease (3.9%), renal calcinosis/stone (3.6%), tubulopathy (9.7%), and chronic kidney disease of unknown etiology (CKDu, 5.8%). The pathogenic variants of 105 monogenetic disorders were identified. Ten distinct genomic disorders were identified as pathogenic copy number variants (CNVs) in 11 patients. The diagnostic yield differed by subgroups, and was highest in those with cystic renal disease (66.3%), followed by tubulopathy (58.4%), GN (57.7%), CKDu (43.5%), SRNS (29.2%), renal calcinosis /stone (29.3%) and CAKUT (8.6%). Reverse phenotyping permitted correct identification in 40 cases with clinical reassessment and unexpected genetic conditions. We present the results of the largest cohort of children with kidney disease in China where diagnostic exome sequencing was performed. Our data demonstrate the utility of family-based exome sequencing, and indicate that the combined analysis of genotype and phenotype based on the national patient registry is pivotal to the genetic diagnosis of kidney disease.

BACKGROUND: Telemedicine is becoming an emerging innovative supplement to the traditional medical system in China. In the present study, we described the rapid implementation of the telemedicine in pediatrics during the coronavirus disease 2019 (COVID-19) outbreak and explored its value in response to the demand for pediatric medical services during the epidemic. METHODS: An Internet-based platform for multidisciplinary online medical consultation was established on February 8, 2020, by a national children’s medical center in China. The medical data of the traditional hospital visits and novel online visits from the first two months (February 8 to March 31) after the establishment of the platform were collected and analyzed. The demographic features, changes in the disease spectrum and characteristics of online medical services were described. RESULTS: The total number of visits was significantly lower (by 75.3%) than that of in the same period in the previous year. The disease spectrum was different with a significant decrease of >95% in the number of patients with infectious or contagious diseases. The online visits accounted for 14.7% of all visits. Online patients came from all over the country, covering 91% of the administrative regions of China, and the largest proportion of inquiries were for infants (33.7%) (P

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. 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. 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). 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 offspring of Robo2 mutant mice usually present with variable phenotypes of congenital anomalies of the kidney and urinary tract (CAKUT). An intrauterine low-protein diet can also cause CAKUT in offspring, dominated by the duplicated collecting system phenotype. A single genetic or environment factor can only partially explain the pathogenesis of CAKUT. The present study aimed to establish an intrauterine low-protein diet roundabout 2 ( Robo2) mutant mouse model and found that the intrauterine low-protein diet led to significantly increased CAKUT phenotypes in Robo2PB/+ mice offspring, dominant by a duplicated collecting system. At the same time, more ectopic and lower located ureteric buds (UBs) were observed in the intrauterine low-protein diet-fed Robo2 mutant mouse model, and the number of UB branches was reduced in the serum-free culture. During UB protrusion, intrauterine low-protein diet reduced the expression of Slit2/Robo2 in Robo2 mutant mice and affected the expression of glial cell-derived neurotrophic factor/Ret, which is a key molecule for metanephric development, with increasing phospho-Akt and phospho-cAMP responsive element-binding protein 3 activity and a reduction of apoptotic cells in embryonic day 11.5 UB tissues. The mechanism by which an intrauterine low-protein diet aggravates CAKUT in Robo2 mutant mice may be related to the disruption of Akt/cAMP responsive element-binding protein 3 signaling and a reduction in apoptosis in UB tissue.

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C16-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days in vitro, with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC., Graphical abstract C16-N hydrogel containing triptolide was created as an intraperitoneal depot for the treatment of orthotopic hepatocellular carcinoma. After intraperitoneal injection, the hydrogel retained in the peritoneal cavity for more than 2 weeks with preferential drug accumulation in the liver, and doubled the median survival time of tumor-bearing mice without noticeable side effects to major organs.Image 1

Objective Nephronophthisis (NPH) is an autosomal recessive cystic kidney disease. Its onset is obscure, and its early clinical manifestations and pathological changes lack specificity, which makes clinical diagnosis difficult. At present, as many as 90 genetic alterations can result in NPH, which exhibits significant genetic heterogeneity. Therefore, high-throughput sequencing technology provides an effective method to identify and characterize novel NPH pathogenic genes when compared to Sanger sequencing. This study summarizes the gene mutations and clinical data of whole exome sequencing, which was used to diagnose 5 NPH patients to improve the understanding of the causative genes and clinical phenotypes of NPH. Materials and methods The clinical manifestations, laboratory examination indexes, and imaging data of 5 patients of NPH were reported. Whole exome sequencing was performed in 5 children, and the causative genes and mutation sites were analyzed by bioinformatics and genetics. The mutation sites were verified in children and their parents using Sanger direct sequencing. Results Among the 5 patients (3 male and 2 female), 2 patients had infantile NPH, and 3 patients had juvenile NPH. The 2 infantile NPH patients were characterized by the onset of liver dysfunction accompanied by hypertension and left ventricular change, and the renal function progressed to end-stage renal disease (ESRD) after 7 months and 9 months, respectively. The 2 cases of infantile NPH had NPHP3 mutations, with one carrying compound heterozygous mutations (c.1358A>G, c.2369A>G) and the other simultaneously carrying a c.1174C>T IVS26-3A>G cleavage site mutation from the father and a nonsense mutation (p.392R>X, 939) from the mother. The 2 juvenile NPH children had entered ESRD at the onset of the disease, including 1 patient with Joubert syndrome. The 2 patients with juvenile NPH had frameshift mutations (c.1583 to 1596: deletion) and homozygous point mutations (7 c.640G>T) of the NPHP1 gene. In addition, another patient with frequent urination and nocturia resulting in stage CKD3 renal function had a complex heterozygous mutation of the NPHP2 gene (c.2686G>A, c.1943A>G). The urine A1MU/creatinine and urinary transferrin increased in all 5 patients without hematuria. Conclusion Whole exome sequencing identified the causative genes of NPH in 5 children. In NPH children with NPHP3 gene mutations, renal functional damage was characterized by early onset and rapid progression to ESRD, often accompanied by liver dysfunction and hypertension.

Proteinuria is an important marker and is closely related to the progressive decline of renal function. Our previous research showed that angiopoietin-like-3 (ANGPTL3) plays a crucial role in proteinuria. In this study, we prepared an antibody against ANGPTL3 coil-coiled domain (ANGPTL3-CCD) and investigated the protective effect of anti-ANGPTL3-CCD antibody in mice with adriamycin-induced nephropathy. Nephropathy was established by adriamycin injection at a dose of 25 mg per kg in 8–12 week-old male mice in the ADR group. Blockade of ANGPTL3 by anti-ANGPTL3-CCD antibody (20 mg per kg) was performed every three days nine times after adriamycin injection in the ADR plus anti-angptl3-antibody group. The anti-ANGPTL3-CCD antibody can specifically recognize ANGPTL3. After anti-ANGPTL3-CCD antibody intervention, the urinary protein level in the ADR plus anti-angptl3-antibody group was significantly lower than that in the ADR group. Serum albumin was higher and triglyceride and total cholesterol were lower in the ADR plus anti-angptl3-antibody group than in the ADR group. The levels of serum creatinine did not significantly differ among the groups. Focal sclerotic glomeruli and podocyte foot processes extensive fusion were found in the renal tissue of the ADR group, whereas no sclerotic glomeruli and only partial fusion were found in the ADR plus anti-angptl3-antibody group. This study demonstrated that the anti-ANGPTL3-CCD antibody ameliorated proteinuria and podocyte dysfunction in adriamycin-induced nephropathy in mice.

Intrauterine low-protein diet can affect kidney development and hence final nephron number. In this study, we reported that intrauterine low-protein diet can cause congenital anomalies of the kidney and urinary tract (CAKUT) phenotypes, which was dominated by the duplicated collecting system phenotype. At the same time, ectopic ureteric buds were increased under intrauterine low-protein diet and the number of UB branches was reduced in the serum-free culture. Intrauterine low-protein diet can change metanephric gene expression. Slit2/Robo2 and Spry1 expression levels were decreased, Ret expression was increased, and downstream p-Akt activity enhanced with apoptosis abnormal in ureteric bud tissue, which may be the mechanisms that intrauterine low-protein diet causes increased incidence of CAKUT in offspring. Thus, we showed correlation between intrauterine low-protein diet and CAKUT in offspring.

Background Angiopoietin-like-3 (Angptl3) knockout is known for its protective effects on podocyte injury and proteinuria in the early stage of adriamycin (ADR) nephropathy. The current study re-evaluated the renoprotective effect of Angptl3 knockout in chronic ADR nephropathy and attempted to explore the mechanism underlying the effect associated with Angptl3 knockout in glomerulosclerosis. Methods B6; 129S5 mice were injected with ADR to induce nephropathy. Kidney structure and serum and urine parameters were observed during long-term follow-up. Cultured primary mouse podocytes were exposed to ADR and analyzed for the expression of some relative proteins. Podocyte loss was analyzed in both in vivo and in vitro experiments. Results Angptl3 knockout attenuated proteinuria and hypoproteinemia, protected renal structure and function, and improved the survival of mice over the whole process of ADR nephropathy. Furthermore, Angptl3 knockout reduced the numbers of the detached and apoptotic cells in the renal tissue and alleviated podocyte loss in mice with ADR chronic nephropathy, thereby, delaying the glomerulosclerosis formation. Additional results in vitro showed that Angptl3 knockout attenuated ADR-induced primary podocyte loss, including podocyte detachment and apoptosis. Conclusion In addition to serving a renoprotective role in the early stage of ADR nephropathy, Angptl3 knockout contributed to disease amelioration throughout the ADR nephropathy process. Angptl3 knockout effectively delayed glomerulosclerosis formation by attenuating podocyte loss through rescuing podocytes from detachment and apoptosis. Angptl3 antagonists or inhibitors might have therapeutic potential in the occurrence and progression of nephropathy. Electronic supplementary material The online version of this article (10.1186/s12882-019-1383-1) contains supplementary material, which is available to authorized users.

Most of the available epidemiological data on peritonitis have been derived from developed countries. Limited data from China have been reported.An 18-year (2001-2018) peritoneal dialysis (PD) program at the Children's Hospital of Fudan University was described, and data on peritonitis were retrospectively analyzed.Since 2001, a program with a comprehensive PD care bundle has been developed, and 283 patients (53.7% male, median age 9.3 years) were enrolled between 2001 and 2018. Among these patients, 117 peritonitis episodes occurred in 68 (24.0%) patients over 4896 patient-months. The peritonitis rate decreased 20-fold from 2.2 episodes per patient-year in 2003 to 0.11 episodes in 2018. The culture-negative rate decreased from 68.7% during 2001-2006 to 18.5% during 2013-2018, and the proportion of gram-negative and fungal infections increased significantly from 6.6 to 33.8% and 0 to 9.2%, respectively (p 0.001). Short stature as height ≤ - 2 SD (OR 2.35, 95% CI 1.30-4.24, p = 0.005) and PD duration ≥ 1 year (OR 3.38, 95% CI 1.76-6.49, p 0.001) were independently associated with a higher risk of developing peritonitis. Of the 117 peritonitis episodes, 9.4% required permanent removal of the catheter, among which half were fungal infections. Patients with peritonitis had a higher risk for PD technique failure (p = 0.006), but there was no difference in estimated patient survival rates and no patient death due to peritonitis.With the successful development of the PD program and care bundles per the International Society of Pediatric Dialysis (ISPD) guidelines, peritonitis rates have been tremendously reduced in the most active pediatric PD center in China. Growth deficits and a long PD duration were risk factors for developing peritonitis, requiring further close monitoring for a better outcome. A higher resolution version of the Graphical abstract is available as Supplementary information.

Objective: To analyse the clinical manifestations, aetiology, prognosis, and risk factors of fungal peritonitis (FP) in children on peritoneal dialysis (PD).Methods: Among 322 children undergoing PD at Children's Hospital of Fudan University, between January 2001 and December 2019, FP cases were retrospectively analysed and compared with those of bacterial peritonitis (BP) to analyse the risk factors of FP.Results: A total of 124 cases of peritonitis were treated, including 11 FP cases in 11 children (0.0019 episodes/patient*month) and 113 BP cases in 64 children (0.02 episodes/patient*month). Among the 11 FP cases, 7 cases (63.64%) were caused by Candida and Candida parapsilosis (5/7) was the most common pathogen of Candida. All FP patients were converted to haemodialysis (HD) and did not resume PD during follow-up. Two patients (18.2%) died after 6 months of HD due to heart failure, 2 patients underwent kidney transplant after 2 years of infection, and the other 7 patients were still on HD. The univariate analysis showed the usage rate of antibiotics in the month before the onset of peritonitis was higher (45.45 vs. 15.93%) and the mean serum albumin was lower (31.4 vs. 34.4 g/L) in the FP group when compared with BP group (P < 0.05), while multivariate analysis showed that serum albumin ≤ 30 g/L was an independent risk factor for FP (odds ratio 4.896, 95% confidence interval 1.335–17.961).Conclusion: FP is a rare complication of PD in children, but it is associated with high technique failure. Attention should be paid to hypoproteinaemia and antibiotic use in children on PD.

Genetic kidney disease is well established as an important cause of pediatric kidney failure, and genetic testing might increase diagnostic accuracy, but evidence is limited. This study was conducted to determine the diagnostic yield and clinical impact of genetic testing for children with kidney failure. Patients who were diagnosed with kidney failure before 19 years of age at Children’s Hospital of Fudan University from 2009 to 2018 and received next-generation sequencing (NGS) were enrolled. The results for likely pathogenic variants in genes known to cause chronic kidney disease (CKD) were analyzed. A molecular diagnosis was identified in 39.9% (75/188) of children with kidney failure. Specific subtype of clinical category was discerned in 54 (72.0%) patients, kidney disease was reclassified in 7 (9.3%) patients, the unknown etiology of 5 (6.7%) patients was molecularly diagnosed, and the clinical diagnoses of the other 9 (12.0%) patients were confirmed. In addition, genetic diagnosis was considered to have contributed to clinical management, including negating the need for kidney biopsy (26/75, 34.7%), avoiding immunosuppressive therapy (24/75, 32.0%), changing surveillance (48/75, 64.0%), guiding specific treatment (21/75, 28.0%), and guiding peri-transplant management and options for kidney transplantation (12/75, 16.0%). Furthermore, cascade testing was subsequently offered to 34.7% (26/75) of families. Genetic testing identified a molecular diagnosis in nearly 40% of children with kidney failure. Our results confirm that in children with kidney failure, genetic testing can not only establish a specific molecular diagnosis, but has a significant impact on clinical management.

Background The caregivers of children on peritoneal dialysis face heavy care burdens and may have a high risk of depression. This study aimed to describe the prevalence and severity of depression and identify its related demographic and socioeconomic factors in the caregivers of children on peritoneal dialysis in China. Methods A multicenter cross-sectional study was conducted in four pediatric dialysis centers in four tertiary children’s hospitals in mainland China. Primary caregivers of children with end-stage kidney disease and currently on peritoneal dialysis were screened and recruited from December 2018 to July 2019. A self-developed questionnaire and the Self-Rating Depression Scale (SDS) were administered to the participants by a trained nurse in each center. The chi-square test or Fisher’s exact test, one-way ANOVA, and the Mann-Whitney U test were used to compare the prevalence of depressive symptoms by demographic features. A multivariate logistic regression analysis was used to identify factors related to depressive symptoms in caregivers of children on peritoneal dialysis. Results One hundred twenty-one caregivers were included in the data analysis. The mean age of the caregivers was 40.1 ± 8.1 years. More than 75% of the participants were female, married, and unemployed. The overall prevalence of depressive symptoms was 59%. In total, 46 (38%), 20 (17%) and 5 (4%) caregivers reported mild, moderate, and severe depressive symptoms, respectively. In the univariate analysis, caregivers with an average household income per month under 4000 RMB and caregivers of children undergoing laparoscopic surgery had a higher prevalence of depressive symptoms. Characteristics such as treatment center, duration on PD, PD modalities, and history of peritonitis episodes showed no difference in terms of the prevalence of depressive symptoms. The multivariate logistic regression analysis demonstrated that an average household income per month under 4000 RMB was the associated factor for caregivers’ depressive symptoms. Conclusions The caregivers of children on peritoneal dialysis in mainland China were socially vulnerable and experienced depression. Those who had a higher average household income were less vulnerable to depression.

Objectives:Nocturnal enuresis (NE) is a common pediatric condition, and desmopressin (dDAVP) is a first-line therapy for NE. The standard initial dosage of dDAVP is 0. 2 mg/day, and most guidelines recommend that the dose should be increased at 0.2 mg increments until dryness is achieved or to the maximal recommended dose. However, previous evidence has shown that this strategy seems insufficient to further improve efficacy and results in unnecessarily high doses for some patients. Our study aimed to assess the efficacy of our modified dDAVP treatment regimen in children with MNE in China and evaluate predictive factors associated with the dDAVP response.Methods:All MNE patients at the Department of Nephrology at Children's Hospital of Fudan University from January to December 2019 were prospectively and consecutively enrolled. dDAVP treatment comprised a dose titration period and a 3-month maintenance period. The efficacy of dDAVP was assessed according to the latest International Children's Continence Society criteria at the end of the study. Predictive factors were evaluated by logistic regression analysis.Results:Overall, 322 MNE patients were enrolled in our study, and 225 (69.9%) completed the study. The intention to treat analysis showed that the overall dDAVP response rate was 69.9%: among these patients 32.3% were complete responders, and 37.6% were partial responders. At the end of the study, 194/225 (86.2%) patients received a final dose of 0.2 mg, 24/225 (10.7%) patients received a final dose of 0.3 mg, and 7/225 (3.1%) patients received a final dose of 0.4 mg. Multivariate analysis showed that patients requiring lower doses to achieve responses were significantly more likely to experience complete response during the maintenance period [odds ratio (OR)=9.683; 95% confidence interval (CI), 2.770–33.846].Conclusions:Our results indicate that the dDAVP treatment regimen provides a comparable efficacy to the international conventional treatment regimen with a lower overall dose. Low-dose responders were likely to achieve a complete response without increasing the dose; in these cases, the maximum dose might not be necessary.

BACKGROUND: Gen1 mutation can cause various phenotypes of congenital anomaly of the kidney and urinary tract (CAKUT). An intrauterine low-protein isocaloric diet can also cause CAKUT phenotypes in offspring. However, single factors such as gene mutation or abnormal environmental factor during pregnancy can only explain part of the pathogenesis of CAKUT. OBJECTIVES: A low-protein isocaloric diet was fed to Gen1-mutant mice throughout pregnancy to establish a Gen1-mutant mouse model exposed to a low-protein isocaloric intrauterine environment. The mice were divided into 4 groups: normal (22%) protein diet (ND) + wild-type mice (CON group), ND + Gen1PB/+ mice (Gen1PB/+ group), low (6%)-protein isocaloric diet (LD) + wild-type mice (LD group), and the LD + Gen1PB/+ groups. METHODS: The experimental design included observing proportion and distribution of CAKUT phenotypes of neonatal mice; evaluating the number of ureteric buds (UBs) on embryonic day (E) 11.5, the location of UBs on E11.5, and length of the common nephric duct (CND); isolating embryonic kidneys on E11.5 from the Gen1PB/+ group and culturing embryonic kidneys in medium containing 10% serum or serum-free medium to observe the branching of UBs; and detecting the p-PLCγ, p-Akt, and p-ERK1/2 in UBs and CND on E11.5, as well as the apoptosis and proliferation of tissues by immunofluorescence staining. RESULTS: We found that the incidence of CAKUT in offspring of Gen1PB/+ mice under an intrauterine low-protein isocaloric diet environment was significantly increased, and a duplicated collecting system was the dominant phenotype of CAKUT. During the early stage of metanephric development, ectopic protrusion of UBs may appear and lower locations of UBs in Gen1PB/+ mice under an intrauterine low-protein isocaloric diet environment and the number of UB branches in the serum-free culture condition significantly decreased. Further examination revealed that p-PLCγ signaling and tissue apoptosis were abnormal in UBs and the CND at the early stage of kidney development. CONCLUSIONS: The aforementioned findings suggest that an intrauterine low-protein isocaloric diet can aggravate the occurrence of CAKUT in Gen1-mutant mice, which might affect key steps in the metanephric development, such as the protrusion of UBs, which might be related to mediate UBs and CND apoptosis through p-PLCγ signaling.

Primary vesicoureteral reflux (VUR) is a common congenital anomaly of the kidney and urinary tract (CAKUT) in childhood. The present study identified the possible genetic contributions to primary VUR in children. Patients with primary VUR were enrolled and analysed based on a national multi-center registration network (Chinese Children Genetic Kidney Disease Database, CCGKDD) that covered 23 different provinces/regions in China from 2014 to 2019. Genetic causes were sought using whole-exome sequencing (WES) or targeted-exome sequencing. A total of 379 unrelated patients (male: female 219:160) with primary VUR were recruited. Sixty-four (16.9%) children had extrarenal manifestations, and 165 (43.5%) patients showed the coexistence of other CAKUT phenotypes. Eighty-eight patient (23.2%) exhibited impaired renal function at their last visit, and 18 of them (20.5%) developed ESRD at the median age of 7.0 (IQR 0.9–11.4) years. A monogenic cause was identified in 28 patients (7.39%). These genes included PAX2 (n = 4), TNXB (n = 3), GATA3 (n = 3), SLIT2 (n = 3), ROBO2 (n = 2), TBX18 (n = 2), and the other 11 genes (one gene for each patient). There was a significant difference in the rate of gene mutations between patients with or without extrarenal complications (14.1% vs. 6%, P = 0.035). The frequency of genetic abnormality was not statistically significant based on the coexistence of another CAKUT (9.6% vs. 5.6%, P = 0.139, Chi-square test) and the grade of reflux (9.4% vs. 6.7%, P = 0.429). Kaplan–Meier survival curve showed that the presence of genetic mutations did affect renal survival (Log-rank test, P = 0.01). PAX2 mutation carriers (HR 5.1, 95% CI 1.3–20.0; P = 0.02) and TNXB mutation carriers (HR 20.3, 95% CI 2.4–168.7; P = 0.01) were associated with increased risk of progression to ESRD. PAX2, TNXB, GATA3 and SLIT2 were the main underlying monogenic causes and accounted for up to 46.4% of monogenic VUR. Extrarenal complications and renal function were significantly related to the findings of genetic factors in children with primary VUR. Like other types of CAKUT, several genes may be responsible for isolated VUR.

Although IgA nephropathy (IgAN) is a common cause of glomerulonephritis in children, the absence of a method to predict disease progression limits personalized risk-based treatment decisions. The adult International IgAN Prediction Tool comprises two validated Cox survival models that predict a 50% decline in estimated glomerular filtration rate (eGFR) or end stage kidney disease (ESKD) using clinical risk factors and Oxford MEST histology scores. Here, we updated the Prediction Tool for use in children using a multiethnic international cohort of 1,060 children with IgAN followed into adulthood. The updated pediatric Prediction Tool had better model fit than the original adult tool with lower Akaike Information Criterion, higher R2D and similar C-statistics. However, calibration showed very poor agreement between predicted and observed risks likely due to the observed disease trajectory in children. Therefore, the Tool was updated using a secondary outcome of a 30% reduction in eGFR or ESKD, resulting in better R2D (30.3%/22.2%) and similar C-statistics (0.74/0.68) compared to the adult tool but with good calibration. The trajectory of eGFR over time in children differed from adults being highly non-linear with an increase until 18 years old followed by a linear decline similar to that of adults. A higher predicted risk was associated with a smaller increase in eGFR followed by a more rapid decline, suggesting that children at risk of a 30% decrease in eGFR will eventually experience a larger 50% decrease in eGFR when followed into adulthood. As such, these two outcomes are analogous between pediatric and adult Prediction Tools. Thus, our pediatric Prediction Tool can accurately predict the risk of a 30% decline in eGFR or ESKD in children with IgAN.

Supramolecular peptide hydrogel (SPH) is a class of biomaterials self-assembled from peptide-based gelators through non-covalent interactions. Among many of its biomedical applications, the potential of SPH in cancer therapy has been vastly explored in the past decade, taking advantage of its good biocompatibility, multifunctionality, and injectability. SPHs can exert localized cancer therapy and induce systemic anticancer immunity to prevent tumor recurrence, depending on the design of SPH. This review first gives a brief introduction to SPH and then outlines the major types of peptide-based gelators that have been developed so far. The methodologies to tune the physicochemical properties and biological activities are summarized. The recent advances of SPH in cancer therapy as carriers, prodrugs, or drugs are highlighted. Finally, the clinical translation potential and main challenges in this field are also discussed.