Steroid-resistant nephrotic syndrome caused by nuclear pore gene NUP133 variation.

Partially enlarged structure of NUP133: wild-type (upper) and mutant p.Lys966Asn (lower).

The influence of delay elimination communication on the prevalence of primary nocturnal enuresis-a survey from Mainland China.

AIMS: A pilot survey shows that primary nocturnal enuresis (PNE) prevalence has increased significantly during the past decade in Mainland China. Whether it is related to the delay of elimination communication (EC) is unclear. This study retrospectively investigated the influence of delayed EC on the PNE prevalence in children and adolescents in mainland China. METHODS: A cross-sectional study of PNE prevalence was performed by distributing 19 500 anonymous self-administered questionnaires to parents in five provinces of mainland China from July 2017 to October 2017. The questionnaires included sociodemographic data, family caregivers' information, and details about the disposable diapers (DD) usage, EC commencement date, psychological disorders, lower urinary tract symptoms, and family history of PNE in children and adolescents. The 2017 PNE prevalence was compared with that of 2006 in Mainland China. RESULTS: The total response rate was 97.04% (18 631 of 19 500) and 92.39% (18 016 of 19 500) qualified for statistical analysis. The PNE prevalence in 2017 has increased significantly compared to that of 2006 (7.30% vs 4.07%, P < 0.001). The PNE prevalence in children with EC starting before 6 months of age was significantly lower than those who start after 12 months of age. The longer DD were used and the later the beginning of EC, the higher the PNE prevalence was found. CONCLUSIONS: The PNE prevalence in Mainland China has increased significantly during the past 10 years. A longer use of DD and later onset of EC may be risk factors for PNE.

[Clinical effect of tacrolimus combined with glucocorticoid in the treatment of IgA nephropathy in children].

OBJECTIVE: To study the clinical effect and safety of tacrolimus (TAC) combined with glucocorticoid (GC) versus mycophenolate mofetil (MMF) combined with GC in the treatment of primary IgA nephropathy (IgAN) in children. METHODS: A retrospective analysis was performed for the clinical data of children with primary IgAN confirmed by renal pathology between January 2012 and December 2017. These children were divided into TAC group and MMF group according to the treatment regimen. Their clinical data before treatment and at 1, 3, and 6 months of treatment were collected, and the remission status of IgAN and adverse reactions were compared between the two groups. RESULTS: A total of 43 children who met the inclusion criteria were enrolled, with 15 children in the TAC group and 28 children in the MMF group. At 1 month of treatment, there was no significant difference in the remission status between the two groups (P>0.05). At 3 and 6 months of treatment, the TAC group had a significantly better remission status than the MMF group (P<0.05). At 1 month of treatment, the TAC group had higher serum albumin levels than the MMF group (P<0.05). Both groups had a significant increase in serum albumin levels at each time point after treatment (P<0.0083) and a significant increase in the glomerular filtration rate (GFR) at 3 and 6 months of treatment (P<0.0083). There was no significant difference in the overall incidence rate of adverse reactions between the two groups (P>0.05), but fungal infection was observed in one child from the TAC group. CONCLUSIONS: TAC combined with GC can effectively reduce urinary protein in children with primary IgAN, and it has a better short-term clinical effect than MMF combined with GC, with good safety.

[Significance of serum cholesterol and fibrinogen in evaluating the risk of glomerulosclerosis in children with nephrotic syndrome].

OBJECTIVE: To investigate the significance of serum cholesterol and fibrinogen (Fib) in evaluating the risk of glomerulosclerosis in children with nephrotic syndrome. METHODS: Sixty-three children with primary nephrotic syndrome were divided into two groups according to their pathological types: minimal change glomerulopathy (MCG) (n=39) and focal segmental glomerulosclerosis (FSGS) groups (n=24). Serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and Fib and 24-hour urinary protein excretion were retrospectively analyzed. RESULTS: Serum levels of TC, non-HDL-C, and LDL-C were significantly higher in the FSGS group than in the MCG group (P<0.05), but there were no significant differences in HDL-C, Fib and 24-hour urinary protein excretion between the two groups (P>0.05). According to the results of logistic regression analysis, high levels of LDL-C, non-HDL-C and TC were risk factors for FSGS (P<0.05). In patients whose proteinuria did not disappear after taking enough glucocorticoid for 4 weeks, the level of non-HDL-C was significantly higher in the FSGS group than in the MCG group (P<0.05); there were no significant differences in TC, LDL-C, HDL-C, and Fib between the MCG and FSGS groups (P>0.05). CONCLUSIONS: Serum cholesterol, especially non-LDL-C, is of great significance in evaluating the risk of glomerulosclerosis in children with nephrotic syndrome. There is no sufficient evidence to support serum Fib as a marker for predicting glomerulosclerosis in these children.

Role of abnormal glycosylated IgA1 and interstitial transformation of glomerular endothelial cells in the development and progression of IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is a common primary renal disease in childhood. METHODS: Twenty blood samples and renal tissue from patients with IgAN, 20 blood samples from healthy children and 10 normal renal tissue were collected. Serum Gd-IgA1 and renal Gd-IgA1, CD31, α-SMA and vimentin were measured. RESULTS: The serum Gd-IgA1 concentration in the IgAN group was significantly higher. Gd-IgA1 was not expressed in normal kidneys, which was positive in the IgAN group. Gd-IgA1 levels in serum and renal tissue were not related. The expression of CD31 decreased significantly in IgAN group, while the expression of α-SMA and vimentin increased significantly. There was no significant correlation between the renal concentration of Gd-IgA1 and CD31, α-SMA and vimentin. CONCLUSION: The increased Gd-IgA1 in the serum and kidney may promote the pathogenesis of IgAN. The serum Gd-IgA1 cannot predict the extent of its deposition in the kidney. Endothelial mesenchymal transition (EndMT) may be involved in the pathogenesis of renal fibrosis in IgAN.

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis: a nationwide retrospective study in China.

BACKGROUND: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. METHODS: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. RESULTS: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. CONCLUSIONS: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB).

[A clinico-pathological comparison between Henoch-Schonlein purpura nephritis and IgA nephropathy in children].

OBJECTIVE: To study the difference in clinico-pathological features between IgA nephropathy (IgAN) and Henoch-Schonlein purpura nephritis (HSPN) in children. METHODS: The medical data of 103 children with HSPN and 61 children with IgAN were retrospectively studied. RESULTS: There were no significant differences in age, sex and disease course between the HSPN and IgAN groups (P>0.05). Clinical classification demonstrated that more severe conditions were found in the IgAN group than in the HSPN group and gross hematuria was more common in the IgAN group (P<0.05). Serum creatinine and cholesterol levels were higher in the IgAN group than in the HSPN group (P<0.05). Fibrinogen-related antigen deposition was more common in the HSPN group, while complement 3(C3) deposition was more common in the IgAN group. Interstitial fibrosis, tubular casts and tubular inflammatory infiltration were also more common in the IgAN group (P<0.05). CONCLUSIONS: Significant clinico-pathological differences can be found between HSPN and IgAN in children, and these differences do not support a one disease entity hypothesis.

Effects of glucocorticoids on leukocytes: Genomic and non-genomic mechanisms.

Glucocorticoids (GCs) have been widely used as immunosuppressants and anti-inflammatory agents to treat a variety of autoimmune and inflammatory diseases, and they fully exert their anti-inflammatory and immune-regulating effects in the body. The effect of GCs on white blood cells is an important part of their action. GCs can cause changes in peripheral blood white blood cell counts by regulating the proliferation, differentiation, and apoptosis of white blood cells. Although the total number of white blood cells, neutrophil counts, lymphocytes, and eosinophils increases, the counts of basic granulocytes and macrophages decreases. In addition, GCs can regulate the activation and secretion of white blood cells, inhibit the secretion of a variety of pro-inflammatory cytokines, the expression of chemokines, and promote the production of anti-inflammatory cytokines. For patients on GC therapy, the effects of GCs on leukocytes were similar to the changes in peripheral blood caused by bacterial infections. Thus, we suggest that clinicians should be more cautious in assessing the presence of infection in children with long-term use of GCs and avoid overuse of antibiotics in the presence of elevated leukocytes. GCs work through genomic and non-genomic mechanisms in the human body, which are mediated by GC receptors. In recent years, studies have not fully clarified the mechanism of GCs, and further research on these mechanisms will help to develop new therapeutic strategies.

Impact of body mass index on primary immunoglobulin A nephropathy prognosis: a systematic review and meta-analysis.

PURPOSE: The impacts of body mass index (BMI) on the prognosis of primary IgA nephropathy (IgAN) remain controversial. This systematic review and meta-analysis aimed to solve these issues. METHODS: We searched the PubMed, EMBASE, and Cochrane Library to screen articles investigating the BMI and primary IgAN. BMI was classified according to the World Health Organization as high (≥ 25.0 kg/m2) and low (< 25.0 kg/m2). The baseline renal indexes and the incidences of adverse renal outcomes were focused on. RESULTS: Six studies with a total of 1723 patients were included in this study. High BMI was demonstrated to be associated with increased baseline levels of serum creatinine (weighted mean difference (WMD) 9.54, 95% confidence interval (CI) 0.63-18.45), blood uric acid (WMD 19.85, 95% CI 10.11-29.59) and urine protein (WMD 0.37, 95% CI 0.21-0.53). Patients with high BMI also showed compromised eGFR at diagnosis (WMD - 8.39, 95% CI - 11.62 to - 5.16) with a higher incidence rate of hypertension (odds ratios (OR) 2.59, 95% CI 1.44-4.66) and higher global optical scores (WMD 1.22, 95% CI 0.70-1.74). Regarding the prognosis, high BMI was significantly associated with the incidence of adverse renal outcomes (OR 2.43, 95% CI 1.66-3.55, P < 0.001) and deteriorated eGFR at the last follow-up (WMD - 11.10, 95% CI - 16.96 to - 5.25, P < 0.001), with non-significantly poorer renal disease-free survival (hazard ratio 1.79, 95% CI 0.58-5.50, P = 0.31). CONCLUSION: High BMI was associated with severe onset and poor prognosis of primary IgAN. The management of BMI could be a novel method to promote the therapeutic outcomes of primary IgAN.

Evaluation of a new frequency-volume chart for children with primary monosymptomatic nocturnal enuresis: a prospective, comparative study.

INTRODUCTION: To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis (PMNE), a new modified 3-day weekend frequency-volume chart (FVC) was designed, and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society (ICCS) recommended voiding diary. METHODS: A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary. The primary outcome measure was the compliance, assessed by comparing the completing index and the quality score of diaries between two groups. The secondary outcome measure was the validity, evaluated by comparing the constituent of subtypes, micturition parameters and response rate to desmopressin. RESULTS: Among the 1200 participants enrolled in the study, 447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary. The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group. In addition, there was no significant difference between these two groups in the subtype classification, or in the response rate to desmopressin. CONCLUSIONS: The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.

Evaluation of ovotoxicity in female mice caused by organic extracts in tap water from Jialing River in Chongqing, China.

BACKGROUND: Recently, toxic effects of widespread organic pollutants have received much attention due to the hazards they pose to female reproductive health. The aim of the present study was to determine the female reproductive toxicity of organic extracts (OE) in tap water from the Jialing River in Chongqing, China. METHODS: In our experiment, Kunming female mice that exhibited normal estrous cycles were randomly divided into 4 groups, which included a control group (OE 0 L/kg bw) as well as low- (OE 12.5 L/kg bw/day), mid- (OE 25 L/kg bw/day), and high-dose (OE 50 L/kg bw/day) groups. Mice were continually administered intraperitoneal injections of OE at different doses for 5 consecutive days. On the 15th and 30th day after treatments, half of the mice were sacrificed separately. RESULTS: The results showed that OE decreased relative ovary weights and prolonged the duration of estrous cycle with concomitant increase in estrous phase. There was a significant decrease in the number of corpora lutea of OE-treated mice, but no significant differences were found in healthy and atretic follicle populations compared to control. Ultrastructure observation regarding granulosa cells of the ovary revealed that OE treatment caused mitochondrial swelling together with endoplasmic reticulum expansion. CONCLUSIONS: All these data indicate that OE could exert adverse effects on the development of ovary and also a slight suppressive effect on reproductive functions.

[Clinical-pathological characteristics of IgM nephropathy in 34 children].

OBJECTIVE: To investigate the clinical pathologic characteristics of IgM nephropathy in children. METHODS: The data of 34 children with IgM nephropathy from the First Affiliated Hospital of Zhengzhou University were retrospectively reviewed. RESULTS: Of the 34 cases of IgM nephropathy, nephrotic syndrome (NS) was clinically presented in 22 cases (64.7%). The renal pathological classification was as follows: minimal change disease (12 cases, 35.3%), minimal change disease with acute renal tubular injury (3 cases, 8.8%), minimal change glomerulonephritis (6 cases, 17.6%), minimal change glomerulernephritis with ischemic renal injury (1 case, 2.9%), mesangial proliferative glomerulonephritis (7 cases, 20.6%), focal segmental glomerulosclerosis (4 cases, 11.8%), focal proliferative glomerulernephritis (1 case, 2.9 %). Glomerular injury score, renal vascular injury score and total renal injury score increased with the increasing IgM deposition. CONCLUSIONS: The majority of children with IgM nephropathy manifest clinically as nephrotic syndrome. The patterns of renal pathology may be varied in children with IgM nephropathy. IgM deposition in the mesenteric area is an important pathologic feature and is related to the degree of renal injury.

[Mobilization effects of SCF along with G-CSF on bone marrow stem cells and endothelial progenitor cells in rats with unilateral ureteral obstruction].

OBJECTIVE: To study the mobilization effects of stem cell factor (SCF) along with granulocyte colony-stimulating factor (G-CSF) on bone marrow stem cells and endothelial progenitor cells in rats with unilateral ureteral obstruction (UUO). METHODS: Fifty-six healthy male Wistar rats were randomly divided into seven groups: control, SCF, G-CSF, SCF+G-SCF, Sham-operated, UUO and UUO+SCF+G-CSF groups (n=8 each). The rats from the control, SCF, G-CSF and SCF+G-CSF groups were hypodermically injected with normal saline (2 mL/kg), SCF (200 microg/kg), G-CSF (200 microg/kg) and SCF along with G-CSF respectively for 5 days. The rats from the UUO and UUO+SCF+G-CSF groups were subjected to the ligation of right ureter and then were hypodermically injected with normal saline (2 mL/kg) and SCF (200 microg/kg)+G-CSF (200 microg/kg) respectively for 5 days. The sham-operated group had the same operative approach as the UUO and the UUO+SCF+G-CSF groups but the right ureter was not ligated. After operation they received a hypodermical injection of 2 mL/kg normal saline for 5 days. Five days later blood samples were collected. The percentages of CD34+ and CD34+/CD133+ cells in intravenous blood mononuclear cells were detected by flow cytometry. Serum contents of glutamate-pyruvate transaminase (GPT), glutamic oxalacetic transaminase (GOT), urea nitrogen and creatinin were measured. RESULTS: Except for the sham-operated group, the other five groups (SCF, G-CSF, SCF+G-SCF, UUO and UUO+ SCF+G-CSF groups) had significantly higher percentage of CD34+ cells and CD34+/CD133+ cells in intravenous blood mononuclear cells than the control group (P < 0.05). There were significant differences in the percentage of CD34+ cells and CD34+/CD133+ cells among the five groups (P < 0.05). The UUO+SCF+G-CSF group showed the highest percentage of CD34+ cells and CD34+/CD133+ cells, followed by the SCF+G-CSF group. There were no significant differences in serum contents of GPT, urea nitrogen and creatinin among the seven groups. Except the UUO group showed higher GOT contents, there were no significant differences in the GOT contents among the other six groups. CONCLUSIONS: The mobilization effects of SCF and G-CSF on bone marrow stem cells and endothelial progenitor cells were not always in paraller. A combination of SCF and G-CSF can effectively mobilize stem cells and endothelial progenitor cells, and side effects were not found in the liver and the kidney.

[Role of mast cells in the development of renal interstitial fibrosis in children with Henoch-Schonlein purpura nephritis].

OBJECTIVE: To investigate the role of mast cells in the development of renal interstitial fibrosis in children with Henoch-Schonlein purpura nephritis (HSPN) and possible mechanisms. METHODS: Paraffin-embedded renal biopsy tissue sections from 20 children with HSPN were examined for the levels of tryptase-beta and transforming growth factor-beta1 (TGF-beta1) by immunohistochemical staining. Mast cells were counted by toluidine blue staining. Masson staining was used to assess the level of renal interstitial fibrosis and renal histopathological scores. Normal renal tissue sections from 5 nephrectomized children for nephroma were used as control group. RESULTS: The percentages of positive tryptase-beta cellsand mast cells and the TGF-beta1 expression in the HSPN group were significantly higher than those in the control group (P < 0.05). The percentages of positive tryptase-beta cells and mast cells and the TGF-beta1 expression in renal tissue were positively correlated with the glomeruli histopathological score (r =0.940, 0.920, 0.937, respectively; P < 0.05) and were also positively correlated with the histopathological score of renal interstitium (r=0.903, 0.859, 0.948, respectively; P < 0.05). The level of renal interstitial fibrosis was positively correlated with the percentages of positive tryptase-beta cells and mast cells and the expression of TGF-beta1 (r =0.790, 0.766, 0.858, respectively; P < 0.05). There was a positive correlation between the percentages of positive tryptase-beta cells and mast cells (r =0.941, P < 0.05), between the percentage of positive tryptase-beta cells and the TGF-beta1 expression (r =0.897, P < 0.05) and between the percentage of positive mast cells and the TGF-beta1 expression (r=0.942, P < 0.05). CONCLUSIONS: Tubulointerstitial mast cell infiltration is associated with the development of renal interstitial fibrosis in children with HSPN. Mast cells together with TGF-beta1 and mast cell-derived tryptase-beta may be involved in the development of the renal interstitial fibrosis in HSPN.

[Progress in phthalate ester toxicity in the female reproductive system].

Phthalates are high-production-volume synthetic chemicals with ubiquitous environmental pollution because of their use in plastics and other common consumer products. Epidemiological evidence suggests the relation between women-exposure and the potential health hazards of Phthalates. Here we review research about how phthalates interact with the female reproductive system in vivo, in vitro models, embryo development toxicity and the mechanisms of female toxicity.