Association of ACTN4 Gene Mutation with Primary Nephrotic Syndrome in Children in Guangxi Autonomous Region, China.

Objective: To investigate the association between ACTN4 gene mutation and primary nephrotic syndrome (PNS) in children in Guangxi Autonomous Region, China. Methods: The high-throughput sequencing technology was used to sequence ACTN4 gene in 155 children with PNS in Guangxi Autonomous Region in China, with 98 healthy children serving as controls. Twenty-three exon-specific capture probes targeting ACTN4 were designed and used to hybridize with the genomic DNA library. The targeted genomic region DNA fragments were enriched and sequenced. The protein levels of ACTN4 in both case and control groups were quantified using ELISA method. Results: Bioinformatics analysis revealed five unique ACTN4 mutations exclusively in patients with PNS, including c.1516G>A (p.G506S) on one exon in 2 patients, c.1442 + 10G>A at the splice site in 1 patient, c.1649A>G (p.D550G) on exon in 1 patient, c.2191-4G>A at the cleavage site in 2 patients, and c.2315C>T (p.A772V) on one exon in 1 patient. The c.1649A>G (p.D550G) and c.2315C>T (p.A772V) were identified from the same patient. Notably, c.1649A>G (p.D550G) represents a novel mutation in ACTN4. In addition, three other ACTN4 polymorphisms occurred in both case and control groups, including c.162 + 6C>T (1 patient in case group and 2 patients in control group), c.572 + 11G>A (1 patient in case group and 2 patients in control group), and c.2191-5C>T (4 patients in the case group and 3 patients in control group). The serum ACTN4 concentration in the case group was markedly higher, averaging 544.7 ng/mL (range: 264.6-952.6 ng/mL), compared with 241.20 ng/mL (range: 110.75-542.35 ng/mL) in the control group. Conclusion: Five ACTN4 polymorphisms were identified among children with PNS in Guangxi Autonomous Region, China, including the novel mutation c.1649A>G. The lower serum levels of α-actinin-4 in the case group suggest that this protein might play a protective role in PNS.

Tumor necrosis factor-α polymorphism and risk of primary nephrotic syndrome: A case-control study and meta-analysis.

BACKGROUND: The current study aims to explore the relationship between tumor necrosis factor-α (TNF-α) polymorphism and the risk of primary nephrotic syndrome (PNS). METHODS: A total of 250 PNS patients were selected for this study, as well as 300 volunteers serving as the control group. TNF-α polymorphism were assessed using the polymerase chain reaction-restriction fragment length polymorphism method. In addition, a meta-analysis was conducted to analyze previously published literature on this topic. RESULTS: No significant differences were observed in the genotypes frequency or alleles frequency among the study populations. Meta-analysis results revealed a positive association between TNF-α rs1800629 polymorphism and allele contrast in African populations (p = 0), homozygote comparison (p = .007), heterozygote comparison (p = .026), recessive genetic model (p = .011), and dominant genetic model (p = .000). CONCLUSIONS: TNF-α rs1800629 polymorphism does not appear to confer any increased risk for PNS.

[Clinical study on growth impairment induced by oral glucocorticoids based on FGF23/Klotho homeostasis observations]. / 基于FGF23/Klothoç¨³æ€è§‚å¯Ÿå£æœç³–çš®è´¨æ¿€ç´ è‡´ç”Ÿé•¿éšœç¢çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To observe the correlation between growth impairment induced by long-term oral glucocorticoids (GC) therapy and the ratio of FGF23/Klotho in children with primary nephrotic syndrome (PNS). METHODS: A prospective study was conducted on 56 children with GC-sensitive PNS who had discontinued GC therapy for more than 3 months and revisited the Department of Pediatrics of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine between June 2022 and December 2022. After monitoring qualitative and quantitative urine protein levels upon admission, the children with proteinuria relapse were treated with GC (GC group; n=29), while those without relapse did not receive GC treatment (non-GC group; n=27). In addition, 29 healthy children aged 3 to prepuberty were selected as the control group. Height, bone age, growth rate, and the FGF23/Klotho ratio were compared among the groups. The correlations of the FGF23/Klotho ratio with height, bone age, and growth rate were analyzed. RESULTS: The FGF23/Klotho ratio in the GC group was significantly higher than that in the non-GC group after 1 month of GC therapy (P<0.05), and the height and bone age growth rates within 6 months were lower than those in the non-GC group (P<0.05). Correlation analysis showed significant negative correlations between the FGF23/Klotho ratio after 1 month of treatment and the growth rates of height and bone age within 6 months in children with PNS (r=-0.356 and -0.436, respectively; P<0.05). CONCLUSIONS: The disturbance in FGF23/Klotho homeostasis is one of the mechanisms underlying the growth impairment caused by long-term oral GC therapy.

Urokinase prophylactic anticoagulation in children with nephrotic syndrome: a multicenter retrospective cohort study.

OBJECTIVE: To analyze the clinical effect of urokinase on the prevention of thrombosis in children with primary nephrotic syndrome. METHODS: A total of 370 children diagnosed with primary nephrotic syndrome (PNS) in the Children's Hospital of Soochow University and Zibo Maternal and Child Health Hospital from January 2018 to December 2022 were selected as the research objects. The patients were divided into a urokinase adjuvant therapy group and non-urokinase adjuvant therapy group according to the application of drugs. The clinical data of the children were collected, including sex, age, drug application, bleeding during treatment, and telephone follow-up, to record whether thromboembolism occurred in the acute stage and remission stage. The clinical pattern of PNS, renal biopsy, histopathological type, and related laboratory indexes before and after treatment were recorded. RESULTS: A total of 313 patients were treated with urokinase and 57 patients were not. More thrombotic events was observed in non-urokinase group compared to the urokinase group(2 versus 0 episodes, p = 0.02). The thrombotic events observed included one patient had pulmonary embolism combined with right ventricular thrombosis, and another had intracranial venous thrombosis. More minor bleeding events occurred in urokinase group compared to the non-urokinase group(7 versus 1 episodes, p = 1.0). No major bleeding events occurred in either group. CONCLUSION: The rational prophylactic use of urokinase anticoagulation in children with PNS can prevent the formation of thromboembolism and has good safety.

Concomitant of Cryptococcal Meningitis and COVID-19 in a Female Patient with Primary Nephrotic Syndrome and Type 2 Diabetes.

Background: Patients with primary nephrotic syndrome (PNS) are at an increased risk of developing various infections due to the long-term use of immunosuppressive agents. Cryptococcal meningitis (CM) is an uncommon but severe complication that can occur in patients with PNS, particularly those receiving immunosuppressive medications. Case Description: This case report describes a middle-aged female patient with PNS and type 2 diabetes mellitus (T2DM) who developed CM. She received a combination regimen of cyclophosphamide and prednisone, achieving partial remission of PNS. However, she later returned to the hospital with high fever and headache. At admission, her nasopharyngeal swab test was positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and she received therapy of dexamethasone and favipiravir, but her fever and headache were not improved. Following a lumbar puncture was performed for her and CM was diagnosed based on a positive Cryptococcus culture in the cerebrospinal fluid. The patient's cyclophosphamides were temporarily discontinued, and antifungal therapy with amphotericin B liposome and fluconazole was initiated. Despite a noticeable increase in her blood glucose levels due to infection during her hospitalization, she showed improvement with intensified glycemic control treatment. The anti-infection showed significant effectiveness, and the patient's proteinuria remained stable during follow-up. Conclusion: The patient with PNS and T2DM was concurrently diagnosed with both CM and coronavirus disease 2019 (COVID-19), marking the first reported case of such co-infections in these patients. Prompt diagnosis and appropriate antifungal therapy are crucial for improved outcomes of PNS patients with CM and COVID-19.

Parenting self-efficacy and parenting stress mediates the effects of the association of perceived social support and readiness for discharge among parents of children with primary nephrotic syndrome.

PURPOSE: To investigate the level of readiness for discharge among parents of children with primary nephrotic syndrome and to explore the mediating role of parenting self-efficacy and parenting stress between perceived social support and readiness for discharge. DESIGN AND METHODS: A cross-sectional study was conducted in five large tertiary general hospitals in Hunan, China. Data related to demographics, perceived social support, parenting self-efficacy, parenting stress, and readiness for discharge were collected from 350 parents of children diagnosed with primary nephrotic syndrome. Path analysis was used to determine the mediating roles of parenting self-efficacy and parenting stress in the relationship between perceived social support and readiness for discharge. RESULTS: Parents of children with nephrotic syndrome in China experienced low perceived social support, low readiness for discharge, and high parenting stress. Factors influencing readiness for discharge include the child's age, duration of illness, first episode or relapse, parental literacy and marital status. Parenting self-efficacy and parenting stress mediated the effects of the association of perceived social support and readiness for discharge. CONCLUSION: Perceived social support influences the readiness of parents of children with nephrotic syndrome. Parenting self-efficacy and parenting stress have a chain mediating effect of the association of perceived social support and readiness for discharge. PRACTICE IMPLICATIONS: This study emphasizes the mediating role of the psychological state of the child's parents. Nurses should take steps to increase perceived social support and parenting self-efficacy of the child's parents and to reduce parenting stress in order to improve readiness for discharge.

The clinical value of 99mTc-DTPA renal dynamic imaging in evaluating AKI in early adult PNS patients / 中国现代医生

@#Objective To explore the clinical value of 99mTc-diethylenetriaminepentaacetic acid(DTPA)renal dynamic imaging in evaluating renal tubulointerstitial injury in early adult primary nephrotic syndrome(PNS)patients.Methods A total of 42 early adult PNS patients were selected as case group,and the diagnostic efficacy of 99mTc-DTPA renal dynamic imaging quantitative indicators and biochemical indicators of serum creatinine(SCr),blood urea nitrogen(BUN),blood uric acid(UA),blood retinol-binding protein(RBP),and blood β2-microglobulin(β2-MG)levels in renal tubulointerstitial injury was analyzed based on pathological results with or without renal interstitial injury as the standard.Results ①The total glomerular filtration rate(GFR),left kidney GFR and right kidney GFR were negatively correlated with blood SCr,BUN and β2-MG levels of patients in case group.②The diagnostic efficiency of total GFR in diagnosis of tubulointerstitial injury in early adult PNS patients is better than that of blood SCr,BUN and β2-MG,total GFR combined with time to peak(Tp),half discharge time(T1/2)and 20 minute residual rate(R20/p)can improve the diagnostic efficiency.Conclusion 99mTc-DTPA renal dynamic imaging is helpful in early diagnosis of tubulointerstitial injury in early adult PNS patients.

Engineering antioxidant ceria-zirconia nanomedicines for alleviating podocyte injury in rats with adriamycin-induced nephrotic syndrome.

BACKGROUND: Primary nephrotic syndrome (PNS) is characterized by edema, heavy proteinuria, hypoalbuminemia and hyperlipidemia. Moreover, podocyte injury is the key pathological change of PNS. Even though the pathophysiological etiology of PNS has not been fully understood, the production of excessive reactive oxygen species (ROS) plays an important role in the development and progression of the disease. Glucocorticoids are the first-line medications for patients with PNS, but their clinical use is hampered by dose-dependent side effects. Herein, we accelerated the rate of conversion from Ce4+ to Ce3+ by doping Zr4+ in ceria-zirconia nanomedicines to treat the PNS rat model by removal of ROS. RESULTS: The engineered Ce0.7Zr0.3O2 (7CZ) nanomedicines significantly improved the ROS scavenging ability of podocytes at a very low dose, enabling effective inhibition of podocyte apoptosis and actin cytoskeleton depolymerization induced by adriamycin (ADR). Accordingly, podocyte injury was effectively alleviated in rat models of ADR-induced nephrotic syndrome, as confirmed by serum tests and renal tissue staining. Moreover, the mRNA sequencing assay revealed the protective molecular signaling pathways of 7CZ nanomedicines in podocytes. CONCLUSION: 7CZ nanomedicines were highly effective in protecting against ADR-induced podocyte injury in vitro and in vivo at a very low concentration.

Influencing Factors of Quality of Life and Prediction Model Building in Patients with Primary Nephrotic Syndrome: A Single-Centre Retrospective Study.

OBJECTIVE: This study aimed to explore the influencing factors of quality of life (QOL) and establish a prediction model in patients with primary nephrotic syndrome (PNS). METHODS: A single-centre retrospective study was conducted on 245 patients with PNS admitted to Zibo Central Hospital from August 2020 to August 2022. According to the 36-Item Short-Form Health Survey (SF-36) for QOL evaluation, the patients were divided into the good QOL group (the total score ≥50 points) and poor QOL group (the total score <50 points). Univariate analysis was conducted by collecting clinical data from patients, and multiple logistic regression analysis was carried out on single factors with statistically significant differences to construct a clinical prediction model. The diagnostic efficacy of the prediction model was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: A total of 245 questionnaires were distributed, and 243 valid questionnaires were recovered, in which 143 cases had good QOL, with an average score of (71.86 ± 10.83) points, and 100 cases had poor QOL, with an average score of (40.03 ± 5.95) points. Statistical differences were observed in age, education level, monthly family average income, payment methods of medical expenses, albumin, 24-hour urinary protein quantification (24 h UPro) and serum uric acid (SUA) in both groups (p < 0.05), whereas no statistical difference was found in gender, body mass index (BMI) and marital status (p > 0.05). The multiple logistic regression analysis showed that age (X1), monthly family average income (X2), payment methods of medical expenses (X3), albumin (X4), 24 h UPro (X5) and SUA (X6) were risk factors for the QOL of patients with PNS, with Y = -12.105 + 0.130X1 + 0.457X2 + 0.448X3 + -0.161X4 + 0.823X5 + 0.025X6 as the regression prediction model. The results of ROC curve showed that the area under the curve (AUC) was 0.987 with standard error of 0.005 (p < 0.001), and 95% CI was 0.976-0.998. CONCLUSIONS: Age, monthly family average income, payment methods of medical expenses, albumin, 24 h UPro and SUA are risk factors that affect the QOL of patients with PNS, and the construction of prediction model has good evaluation value and can provide a reference for clinical practice.

Influencing Factors of Quality of Life and Prediction Model Building in Patients with Primary Nephrotic Syndrome: A Single-Centre Retrospective Study

Objective: This study aimed to explore the influencing factors of quality of life (QOL) and establish a prediction model in patients with primary nephrotic syndrome (PNS). Methods: A single-centre retrospective study was conducted on 245 patients with PNS admitted to Zibo Central Hospital from August 2020 to August 2022. According to the 36-Item Short-Form Health Survey (SF-36) for QOL evaluation, the patients were divided into the good QOL group (the total score ≥50 points) and poor QOL group (the total score <50 points). Univariate analysis was conducted by collecting clinical data from patients, and multiple logistic regression analysis was carried out on single factors with statistically significant differences to construct a clinical prediction model. The diagnostic efficacy of the prediction model was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 245 questionnaires were distributed, and 243 valid questionnaires were recovered, in which 143 cases had good QOL, with an average score of (71.86 ± 10.83) points, and 100 cases had poor QOL, with an average score of (40.03 ± 5.95) points. Statistical differences were observed in age, education level, monthly family average income, payment methods of medical expenses, albumin, 24-hour urinary protein quantification (24 h UPro) and serum uric acid (SUA) in both groups (p < 0.05), whereas no statistical difference was found in gender, body mass index (BMI) and marital status (p > 0.05). The multiple logistic regression analysis showed that age (X1), monthly family average income (X2), payment methods of medical expenses (X3), albumin (X4), 24 h UPro (X5) and SUA (X6) were risk factors for the QOL of patients with PNS, with Y = –12.105 + 0.130X1 + 0.457X2 + 0.448X3 + –0.161X4 + 0.823X5 + 0.025X6 as the regression prediction model (AU)

Incidence of thromboembolism in children with primary nephrotic syndrome: a systematic review and metaanalysis.

OBJECTIVE: To estimate the incidence of thromboembolism in children with primary nephrotic syndrome with Meta-analysis. METHODS: Relevant studies published from January 1, 1980 to December 31, 2021 were retrieved from Pubmed, Web of science, Cochrane library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database(VIP) and Wangfang Database. Quality evaluation of the literatures included was conducted according to Agency for Healthcare Research and Quality(AHRQ) assessment tool, followed by data extraction and Meta-analysis with software RevMan 5.3. RESULTS: A total of seven studies involving 3675 subjects were included. The overall prevalence was 4.9% with 95% CI of 2.83 to 7.05.However, a significant heterogeneity (P < 0.001) was observed with I2 = 89%. The prevalence of venous thromboembolism was 3.3% with 95% CI of 1.7 to 4.9. The prevalence of arterial thromboembolism was 0.5% with 95% CI of 0.2 to 1.4. CONCLUSION: Children with nephrotic syndrome are prone to thromboembolism, and it may lead to disability or death, therefore prevention measures is critical to decreasing the prevalence of thromboembolism.

Primary membranous nephrotic syndrome with chylothorax as first presentation: A case report and literature review.

BACKGROUND: Primary membranous nephrotic syndrome with chylothorax as the first manifestation is an unusual condition. To date, only a few cases have been reported in clinical practice. CASE SUMMARY: The clinical data of a 48-year-old man with primary nephrotic syndrome combined with chylothorax admitted to the Department of Respiratory and Critical Care Medicine of Shaanxi Provincial People's Hospital were retrospectively analysed. The patient was admitted to the hospital for 12 d due to shortness of breath. Imaging showed pleural effusion, laboratory tests confirmed true chylothorax, and renal biopsy revealed membranous nephropathy. After primary disease treatment and early active symptom treatment, the prognosis of the patient was good. This case suggests that chylothorax is a rare complication of primary membranous nephrotic syndrome in adults, and early lymphangiography and renal biopsy can assist in the diagnosis when there are no contraindications. CONCLUSION: Primary membranous nephrotic syndrome combined with chylothorax is rare in clinical practice. We report a relevant case to provide case information for clinicians and to improve diagnosis and treatment.

Primary nephrotic syndrome relapse within 1 year after glucocorticoid therapy in children is associated with gut microbiota composition at syndrome onset.

BACKGROUND: Children with primary nephrotic syndrome (PNS) who relapse after glucocorticoid therapy are shown to have a decreased total proportion of butyrate-producing bacteria in the gut at onset. Glucocorticoid treatment changes the gut microbiota composition. It is unclear whether gut microbiota at remission right after therapy and gut bacteria other than butyrate-producing bacteria are associated with PNS relapse. METHODS: PNS relapse of paediatric patients within 1 year after glucocorticoid therapy was recorded. The gut microbiota composition, profiled with 16S rRNA gene V3-V4 region sequencing, was compared between relapsing and non-relapsing PNS children at onset before glucocorticoid treatment (preT group) and in PNS children at remission right after treatment (postT group), respectively. RESULTS: The gut microbiota composition of postT children significantly differed from that of preT children by having lower levels of Bacteroides, Lachnoclostridium, Flavonifractor, Ruminococcaceae UBA1819, Oscillibacter, Hungatella and Coprobacillus and higher levels of Ruminococcaceae UCG-013 and Clostridium sensu stricto 1 group. In the preT group, compared with non-relapsing patients, relapsing patients showed decreased Blautia, Dialister and total proportion of butyrate-producing bacteria and increased Oscillibacter, Anaerotruncus and Ruminococcaceae UBA1819. However, relapsing and non-relapsing postT children showed no difference in gut microbiota composition. CONCLUSIONS: PNS relapse-associated gut microbiota dysbiosis at onset, which includes alterations of both butyrate-producing and non-butyrate-producing bacteria, disappeared right after glucocorticoid therapy. It is necessary to study the association of the longitudinal changes in the complete profiles of gut microbiota after glucocorticoid treatment with later PNS relapse.

Left ventricular global longitudinal strain can detect subclinical left ventricular systolic dysfunction in adult patients with primary nephrotic syndrome.

It has been shown that there is an increased risk of cardiovascular events such as heart failure and death in nephrotic syndrome. Left ventricle global longitudinal strain (LVGLS) is a more sensitive measure of assessing myocardial dysfunction and is more reproducible than left ventricle ejection fraction (LVEF%). LVGLS can detectsubclinical deterioration in the left ventricle early. In this study, we aimed to investigate LVGLS in Primary Nephrotic Syndrome (PNS) patients with normal LVEF%. Patients with histopathologically confirmed PNS were evaluated for this prospective single-center study. Patients with similar age and gender characteristics without nephrotic syndrome were included as the control group. LVGLS measurements were performed by 2D speckle tracking echocardiography. A total of 171 patients, 57 with PNS and 114 in the control group, were included in the study. The mean age was 38±12 years in the study population, and 95(56%) of the patients were women. LVEF% was 60.2±4.2 in the PNS group and 61.1±3.2 in the control group, and there was no significant difference between the two groups (p=0.111). LVGLS was found to be significantly lower in the PNS group (-19.3±2.3% vs.-20.8±1.5 %, p<0.001). A significant relationship was observed between PNS and LVGLS in the multivariable linear regression analysis (ß= 4.428, CI 95% =0.57?1.48, p<0.001). A significant relationship was observed between PNS and LVGLS, and LVGLS was found to be lower in PNS patients. In patients with PNS, subclinical left ventricular systolic dysfunction may be detected in the early period by measuring LVGLS.

Significance of PLCE1 gene polymorphism detection in children with primary nephrotic syndrome in Guangxi Zhuang Autonomous Region / 中华实用儿科临床杂志

Objective:To investigate the correlation between the single nucleotide polymorphism (SNP) of the PLCE1 gene and children with primary nephrotic syndrome (PNS) in Guangxi Zhuang Autonomous Region. Methods:This study was a retrospective study, a case-control study was used to select 155 cases of PNS in Guangxi Zhuang children attending the Affiliated Hospital of Youjiang Medical University for Nationalities from January 2017 to January 2021 (PNS group), and 100 healthy Guangxi Zhuang children who were physically examined during the same period (healthy control group). Genotyping of PLCE1 SNP rs3765524, and rs2274223 were performed using the second-generation gene sequencing technology, and their correlation with the development of PNS was analyzed. Logistic regression analysis was used for correlation analysis, and Chi- square test or Fisher′ s exact probability method was used for comparison between groups. Results:(1)Compared with the healthy control group, PLCE1 rs3765524 was correlated with the risk of PNS in children of PNS group, and the TT genotype may reduce the risk of PNS in the co-dominant model ( OR=0.435, 95% CI: 0.238-0.794, P=0.007). There were no significant differences in the genotype of PLCE1 rs2274223 and the frequency of allele distribution between PNS group and healthy control group (all P>0.05). (2) A strong linkage disequilibrium existed at PLCE1 SNP rs3765524 and rs2274223.(3) There were no significant differences in the frequency of the distribution of haplotypes AC, AT and GT between PNS group and healthy control group (all P>0.05). Conclusions:PLCE1 SNP rs3765524 is correlated with the risk of PNS in children in Guangxi Zhuang Autonomous Region, and the TT genotype may be a protective factor for PNS in children in Guangxi Zhuang Autonomous Region.

Acute Kidney Injury Caused by Renin-Angiotensin System Inhibitors During Minimal Change Disease Treatment.

A 76-year-old Japanese man with nephrotic syndrome was admitted to our department for treatment. After his admission, he was administered prednisolone (PSL) at 40 mg/day, and a percutaneous renal biopsy was performed. However, on the first day of admission, his urinary protein decreased from 5.05 g/gCr to 1.85 g/gCr. On the fourth day of admission, his urinary protein further decreased to 0.38 g/gCr and the patient developed acute kidney injury (AKI). Renin-angiotensin system (RAS) inhibitors were suspected to be the cause of AKI; therefore, they were discontinued. After the renal function improved, the urinary protein worsened again to 5.49 g/gCr. Renal pathology suggested minimal change disease (MCD); therefore, PSL was continued. The patient's urinary protein subsequently improved and he had no renal function impairment. Minimal change disease can be complicated by AKI through intravascular volume depletion caused by high urinary protein and hypoalbuminemia. However, when MCD is complicated by RAS inhibitor-associated AKI, the urinary protein may notably decrease, and the patient may present with an atypical course of MCD-associated AKI.

Study on the relationship between nephrotic syndrome and atopic diseases in childhood.

Objective: The present study aimed to explore the relationship between nephrotic syndrome and atopic diseases in childhood. Methods: From 2018 to 2019, 234 children with first-onset primary nephrotic syndrome (PNS) were selected for observation and long-term follow-up, and the clinical and laboratory data. To compare the levels of total serum IgE, histamine and bradykinin of the same children at the time of first onset, remission and relapse of PNS. The extent of podocyte foot process effacement was compared between the urinary protein negative-conversion group and the proteinuric group with the NS range. The correlation between the urine protein quantification and the extent of foot process effacement was also observed. Results: (1) The mean age of 234 children with first-onset PNS was 4.82 ± 3.63 years, with a male to female ratio of 162/72. (2) There were 109 cases (46.58%) with concomitant atopic diseases (AD) and 151 cases (64.53%) with elevated levels of total serum IgE. There were 136 cases with recurrence during the follow-up, of which recurrence due to allergy-related factors was greater than that due to infection-related factors. (3) The total IgE and bradykinin serum levels were significantly higher in children with first-onset PNS and recurrent PNS compared with those in remission, and the differences were statistically significant (P < 0.05). The level of histamine in children with first-onset PNS was higher than that in children with remission (P < 0.05), and there was no significant difference in the level of histamine between children in the recurrence group and those in the remission group (P > 0.05). (4) There was no significant difference in the extent of foot process effacement between the urinary protein negative-conversion group and the proteinuric group with the NS range. There was no significant correlation between the proteinuria quantification and the extent of foot process effacement. Conclusion: There existed a high co-morbidity with AD in children with PNS, and allergy-related factors might be an important recurrence factor in children with PNS. The injury to the filtration barrier in MCD might not only be correlated with podocyte lesions but also with some serum permeability factors. Serum IgE, histamine, and bradykinin might be the plasma permeability factors in children with PNS.

Clinical effect of different prednisone regimens in the treatment of children with primary nephrotic syndrome and risk factors for recurrence. / ä¸åŒæ–¹æ¡ˆæ³¼å°¼æ¾æ²»ç–—å„¿ç«¥åŽŸå‘æ€§è‚¾ç— ç»¼åˆå¾çš„ç–—æ•ˆåŠå¤å‘å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To study the clinical effect of full-dose prednisone for 4 or 6 weeks in the treatment of children with primary nephrotic syndrome and its effect on recurrence. METHODS: A prospective non-randomized controlled clinical trial was performed on 89 children who were hospitalized and diagnosed with incipient primary nephrotic syndrome from December 2017 to May 2019. The children were given prednisone of 2 mg/(kg·day) (maximum 60 mg) for 4 weeks (4-week group) or 6 weeks (6-week group), followed by 2 mg/(kg·day) (maximum 60 mg) every other day for 4 weeks and then a gradual reduction in dose until drug withdrawal. The children were regularly followed up for 1 year. The two groups were compared in terms of the indices including remission maintenance time and recurrence rate. A Cox regression analysis was used to assess the risk factors for recurrence. RESULTS: Within 3 months after prednisone treatment, the 4-week group had a significantly higher recurrence rate than the 6-week group (P<0.05). After 1-year of follow-up, there was no significant difference between the two groups in the recurrence rate, remission maintenance time, and recurrence frequency (P>0.05). The risk of recurrence increased in children with an onset age of ≥6 years or increased 24-hour urinary protein (P<0.05). CONCLUSIONS: For the treatment of incipient primary nephrotic syndrome, full-dose prednisone regimen extended from 4 weeks to 6 weeks can reduce recurrence within 3 months. The children with an onset age of ≥6 years or a high level of urinary protein should be taken seriously in clinical practice, and full-dose prednisone treatment for 6 weeks is recommended to reduce the risk of recurrence.

Quantitative vessel density analysis of macular and peripapillary areas by optical coherence tomography angiography in adults with primary nephrotic syndrome.

PURPOSE: To compare the microvascular parameters of macular and peripapillary areas in adults with primary nephrotic syndrome (PNS) and healthy controls (HCs). METHODS: In this cross-sectional study, optical coherence tomography angiography (OCTA) was used to evaluate the changes in retinal microvascular in 37 adult patients with PNS and 30 HCs in this study. All subjects underwent OCTA for measuring vascular density (VD), perfusion density (PD), and foveal avascular zone (FAZ) in the superficial capillary plexus (SCP) and optical coherence tomography (OCT) for measuring central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness. The following clinical data of the PNS group were collected: hemoglobin, platelet, total protein, albumin, prealbumin, creatinine, urea nitrogen, glomerular filtration rate, blood lipid, urinary protein, urine microalbumin, urine microalbumin/creatinine, 24-h urine volume, and 24-h urine protein quantification. The OCTA data were compared between patients with PNS and HCs, and the correlation between the OCTA data and clinical data was analyzed in the PNS group. RESULTS: VD and PD in the macular area of the PNS group were significantly lower than those in the HC group (VD: 17.025 ± 2.229 vs. 18.290 ± 0.721, P = 0.001; PD: 0.417 ± 0.058 vs. 0.450 ± 0.019, P = 0.003). No significant differences in the FAZ area and perioptic disc microvascular parameters were observed between the two groups, and patients in the PNS group showed consistent changes in the left and right eyes. VD and PD in the central macular area were positively correlated with plasma prealbumin level (VD: ρ = 0.541, P = 0.001; PD: ρ = 0.562, P < 0.001) and negatively correlated with urinary protein level (VD: ρ = -0.579, P < 0.001; PD: ρ = -0.596, P < 0.001). CONCLUSIONS: In adult patients with PNS, the decrease in VD and PD was mainly occurred in the macular area. Partly vascular density of the macular area was positively correlated with plasma prealbumin level and negatively correlated with urinary protein level. OCTA provides a convenient, non-invasive and effective method for evaluating and monitoring retinal microcirculation damage in patients with PNS.

Population Pharmacokinetic Evaluation with External Validation of Tacrolimus in Chinese Primary Nephrotic Syndrome Patients.

PURPOSE: The generalizability of numerous tacrolimus population pharmacokinetic (popPK) models constructed to promote optimal tacrolimus dosing in patients with primary nephrotic syndrome (PNS) is unclear. This study aimed to evaluate the predictive performance of published tacrolimus popPK models for PNS patients with an external data set. METHODS: We prospectively collected 223 concentrations from 50 Chinese adult patients with PNS who were undergoing tacrolimus treatment. Data on published tacrolimus popPK models for adults and children with PNS were extracted from the literature. Model predictability was evaluated with prediction-based and simulation-based diagnostics and Bayesian forecasting. RESULTS: In prediction-based evaluation, none of the 11 identified published popPK models of tacrolimus had met a predefined criteria of a mean prediction error ≤ ± 20%, and the prediction error within ± 30% of the identified models didn't exceed 50%. Simulation-based diagnostics also indicated unsatisfactory predictability. Bayesian forecasting demonstrated amelioration in the model predictability with the inclusion of 2-3 prior observations. Moreover, the predictive performance of nonlinear models was not better than that of one-compartment models. CONCLUSIONS: The prediction of tacrolimus concentrations for patients with PNS remains challenging; published models are not applicable for extrapolation to other hospitals. Bayesian forecasting significantly improved model predictability and thereby helped to individualize tacrolimus dosing.