Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

Efficacy and safety of multi-target therapy in children with lupus nephritis.

BACKGROUND: To analyze the efficacy and safety of multi-target therapy in children with lupus nephritis (LN). METHODS: In our retrospective study from January 2009 to December 2021, the multi-target therapy of glucocorticoids, MMF and tacrolimus was adopted as induction therapy or re-induction therapy for 36 LN children who had combined proliferative and membranous LN or for who were ineffective to combination therapy of glucocorticoids with IV-CYC or MMF for at least 6 months. The clinical and pathological data were collected and analyzed. RESULTS: The levels of 24-h urinary protein, anti-dsDNA antibody and SLE disease activity index were decreased, while the levels of albumin and complement 3 were increased after multi-target therapy. More than 90% of LN children achieved partial or complete remission within 6 months. In terms of adverse effects, there was no significant difference between the level of eGFR before and after multi-target therapy. During the follow-up period, four children had infection, two children had hyperuricemia, and one child had liver dysfunction. All of them improved after symptomatic therapy. CONCLUSIONS: Multi-target therapy could be an effective treatment option with minimal adverse effects for LN children who are refractory to initial first-line induction therapies or had combined proliferative and membranous LN. IMPACT: The multi-target therapy of glucocorticoids, mycophenolate mofetil and tacrolimus was adopted in 36 children with lupus nephritis. Multi-target therapy could be an effective treatment option for lupus nephritis children who are refractory to initial first-line induction therapies or had combined proliferative and membranous lupus nephritis. Adverse effects of multi-target therapy were infrequent and minimal that can be improved by symptomatic therapy.

Incidence of relapse and frequently relapsing/steroid-dependent nephrotic syndrome in Chinese children with steroid-sensitive nephrotic syndrome: A cohort study.

AIM: This study aimed to investigate the incidence of relapse and FR/SDNS in Chinese children with SSNS and to develop clinical prediction models for relapse and FR/SDNS. METHODS: This retrospective cohort study involved 339 newly onset SSNS patients between 2006 and 2016. The incidence of relapse and FR/SDNS were estimated using the Kaplan-Meier method. Prediction models were constructed based on Cox proportional-hazards regression. RESULTS: The median follow-up time was 8.7 years. The cumulative incidence of relapse at 1-, 2-, and 5-year was 51.0%, 62.5%, and 66.6%. The cumulative incidence of FR/SDNS at 1-, 2-, and 5-year was 18.4%, 29.0%, and 32.9%. The final prediction model for first relapse included four variables (serum albumin, triglycerides, IgM, and time to first remission). The model's discriminative ability was low (Harrell's C index = 0.62). The final prediction model for FR/SDNS included four variables (serum albumin, lipoprotein(a), time to first remission, and time to first relapse). The discrimination and calibration of the prediction model for FR/SDNS were acceptable (Harrell's C index = 0.73, Brier score at 1- and 2-year were 0.11 and 0.17). CONCLUSION: The first relapse and FR/SDNS mainly occurred in the first 2 years after initial SSNS onset. The prediction model for relapse developed using common clinical parameters performed poorly, while the prediction model for FR/SDNS might be useful.

De novo transcriptome revealed genes involved in anthocyanin biosynthesis, transport, and regulation in a mutant of Acer pseudosieboldianum.

BACKGROUND: Acer pseudosieboldianum is a kind of excellent color-leafed plants, and well known for its red leaves in autumn. At the same time, A. pseudosieboldianum is one of the native tree species in the northeast of China, and it plays an important role in improving the lack of color-leafed plants in the north. In previous study, we found a mutant of the A. pseudosieboldianum that leaves intersect red and green in spring and summer. However, it is unclear which genes cause the color change of mutant leaves. RESULTS: In order to study the molecular mechanism of leaf color formation, we analyzed the leaves of the mutant group and the control group from A. pseudosieboldianum by RNA deep sequencing in this study. Using an Illumina sequencing platform, we obtained approximately 276,071,634 clean reads. After the sequences were filtered and assembled, the transcriptome data generated a total of 70,014 transcripts and 54,776 unigenes, of which 34,486 (62.96%) were successfully annotated in seven public databases. There were 8,609 significant DEGs identified between the control and mutant groups, including 4,897 upregulated and 3,712 downregulated genes. We identified 13 genes of DEGs for leaf color synthesis that was involved in the flavonoid pathway, 26 genes that encoded transcription factors, and eight genes associated with flavonoid transport. CONCLUSION: Our results provided comprehensive gene expression information about A. pseudosieboldianum transcriptome, and directed the further study of accumulation of anthocyanin in A. pseudosieboldianum, aiming to provide insights into leaf coloring of it through transcriptome sequencing and analysis.

Application of adrenocorticotropic hormone in recurrent focal segmental glomerulosclerosis post-transplantation: A case report and literature review.

BACKGROUND: The recurrence rate of focal segmental glomerulosclerosis (FSGS) post-renal transplantation is as high as 30%-50%. However, the pathogenesis is unclear. At present, there is no unified standard for the treatment of recurrent FSGS post-transplantation. Its treatment is full of risks and challenges. METHODS: We report a child with recurrent FSGS with massive proteinuria 6~9 g/m2 /day and resistance to plasma exchange (PE) and rituximab (RTX). On the basis of receiving anti-rejection therapy of prednisone, tacrolimus, and mycophenolate mofetil (MMF), we treated the child with adrenocorticotropic hormone (ACTH), and reviewed the literature on the application of ACTH in the recurrence of FSGS post-transplantation. RESULTS: After 1 year of treatment with ACTH, the patient's urinary protein decreased and fluctuated between 0.6 and 1.1 g/m2 /day. The albumin (ALB) and cholesterol (CHOL) returned to the normal range. The patient achieved complete remission after 19 months of ACTH treatment and maintained until now. There was no obvious adverse reaction. Literature review showed that up to February 2021, a total of 8 studies showed the use of ACTH in kidney transplant patients, and all the patients in the study achieved remission. CONCLUSIONS: ACTH is a potential option for treating recurrent FSGS post-transplantation with fewer side effects and relatively safe for patients. However, further evaluation is needed to better adapt to different populations.

Classification and rising medication therapy in stiff skin syndrome: A case report and literature review.

Stiff skin syndrome (SSS) is a rare disorder characterized by skin induration and limited joint mobility in the absence of visceral, musculoskeletal, vascular, or immunologic abnormalities. Distinctive subsets of SSS could be distinguished by various manifestation and mechanism, which accounts for the high heterogeneity in SSS cases. Although rehabilitation training remains the mainstay of management, rising medications has drawn awareness in recent years, owing to the potential efficacy. Nevertheless, experience was limited, especially in widespread SSS. We report on a 5-year-old girl with widespread SSS, whose lesion stopped progressing after combination therapy by mycophenolic acid (MPA) and losartan (LST) in addition to rehabilitation exercise. Despite limited experience, a combined therapy of MPA and LST seems to be effective in retarding progression of widespread SSS.

De novo transcriptome sequencing and anthocyanin metabolite analysis reveals leaf color of Acer pseudosieboldianum in autumn.

BACKGROUND: Leaf color is an important ornamental trait of colored-leaf plants. The change of leaf color is closely related to the synthesis and accumulation of anthocyanins in leaves. Acer pseudosieboldianum is a colored-leaf tree native to Northeastern China, however, there was less knowledge in Acer about anthocyanins biosynthesis and many steps of the pathway remain unknown to date. RESULTS: Anthocyanins metabolite and transcript profiling were conducted using HPLC and ESI-MS/MS system and high-throughput RNA sequencing respectively. The results demonstrated that five anthocyanins were detected in this experiment. It is worth mentioning that Peonidin O-hexoside and Cyanidin 3, 5-O-diglucoside were abundant, especially Cyanidin 3, 5-O-diglucoside displayed significant differences in content change at two periods, meaning it may be play an important role for the final color. Transcriptome identification showed that a total of 67.47 Gb of clean data were obtained from our sequencing results. Functional annotation of unigenes, including comparison with COG and GO databases, yielded 35,316 unigene annotations. 16,521 differentially expressed genes were identified from a statistical analysis of differentially gene expression. The genes related to leaf color formation including PAL, ANS, DFR, F3H were selected. Also, we screened out the regulatory genes such as MYB, bHLH and WD40. Combined with the detection of metabolites, the gene pathways related to anthocyanin synthesis were analyzed. CONCLUSIONS: Cyanidin 3, 5-O-diglucoside played an important role for the final color. The genes related to leaf color formation including PAL, ANS, DFR, F3H and regulatory genes such as MYB, bHLH and WD40 were selected. This study enriched the available transcriptome information for A. pseudosieboldianum and identified a series of differentially expressed genes related to leaf color, which provides valuable information for further study on the genetic mechanism of leaf color expression in A. pseudosieboldianum.

De novo transcriptome sequencing of Acer palmatum and comprehensive analysis of differentially expressed genes under salt stress in two contrasting genotypes.

Maple (Acer palmatum) is an important species for landscape planting worldwide. Salt stress affects the normal growth of the Maple leaf directly, leading to loss of esthetic value. However, the limited availability of Maple genomic information has hindered research on the mechanisms underlying this tolerance. In this study, we performed comprehensive analyses of the salt tolerance in two genotypes of Maple using RNA-seq. Approximately 146.4 million paired-end reads, representing 181,769 unigenes, were obtained. The N50 length of the unigenes was 738 bp, and their total length over 102.66 Mb. 14,090 simple sequence repeats and over 500,000 single nucleotide polymorphisms were identified, which represent useful resources for marker development. Importantly, 181,769 genes were detected in at least one library, and 303 differentially expressed genes (DEGs) were identified between salt-sensitive and salt-tolerant genotypes. Among these DEGs, 125 were upregulated and 178 were downregulated genes. Two MYB-related proteins and one LEA protein were detected among the first 10 most downregulated genes. Moreover, a methyltransferase-related gene was detected among the first 10 most upregulated genes. The three most significantly enriched pathways were plant hormone signal transduction, arginine and proline metabolism, and photosynthesis. The transcriptome analysis provided a rich genetic resource for gene discovery related to salt tolerance in Maple, and in closely related species. The data will serve as an important public information platform to further our understanding of the molecular mechanisms involved in salt tolerance in Maple.

Twenty-eight-year review of childhood renal diseases from renal biopsy data: A single centre in China.

AIM: The aim of the present study was to investigate the clinicopathologic characteristics of biopsy-proven childhood renal diseases and to compare the trends and changes during two different time intervals between 1984 and 2011 at the First Affiliated Hospital of Sun Yat-sen University in China. METHODS: We retrospectively analyzed kidney biopsy data from children with renal diseases and compared the data during two time intervals, namely 1984-1997 and 1998-2011. RESULTS: A total of 1313 children were enrolled in the present study. There were 921 children with primary glomerular disease (PGD) and 312 children with secondary glomerular disease (SGD), accounting for 70.1% and 23.8% of participants, respectively. The major clinical manifestation of PGD was nephrotic syndrome (NS), which accounted for 31.2% of cases, while the main aetiology of SGD was lupus nephritis (40.7%). The main biopsy patterns of PGD were IgA nephritis (27.6%), minimal change disease (24.0%), and mesangial proliferative glomerulonephritis (16.9%). PGD was the major class of disease in both time intervals, but the ratio of PGD decreased over time, while the ratio of SGD and other glomerular diseases increased. PGD was also the major class of disease in each age group; however, the incidence of PGD decreased with increasing age. CONCLUSION: The incidence patterns of paediatric renal diseases changed over the 28-year period of this study. Our results show that different renal diseases characterize different age intervals. Furthermore, there are several associations between clinical presentation and biopsy features in childhood renal disease.

[Heavy metal poisoning and renal injury in children].

Along with global environmental pollution resulting from economic development, heavy metal poisoning in children has become an increasingly serious health problem in the world. It can lead to renal injury, which tends to be misdiagnosed due to the lack of obvious or specific early clinical manifestations in children. Early prevention, diagnosis and intervention are valuable for the recovery of renal function and children's good health and growth. This paper reviews the mechanism of renal injury caused by heavy metal poisoning in children, as well as the clinical manifestations, diagnosis, and prevention and treatment of renal injury caused by lead, mercury, cadmium, and chromium.

Silicon Hybridization for the Preparation of Room-Temperature Curing and High-Temperature-Resistant Epoxy Resin.

Specialized epoxy resin, capable of achieving room-temperature profound curing and sustaining prolonged exposure to high-temperature environments, stands as a pivotal material in modern high-end manufacturing sectors including aerospace, marine equipment fabrication, machinery production, and the electronics industry. Herein, a silicon-hybridized epoxy resin, amenable to room-temperature curing and designed for high-temperature applications, was synthesized using a sol-gel methodology with silicate esters and silane coupling agents serving as silicon sources. Resin characterization indicates a uniform distribution of silicon elements in the obtained silicon hybrid epoxy resin. In comparison to the non-hybridized epoxy resin, notable improvements are observed in room-temperature curing performance, heat resistance, and mechanical strength.

Physiological effects of combined NaCl and NaHCO3 stress on the seedlings of two maple species.

Salt stress impacts growth and physiological processes in plants, and some plants exposed to salt stress will produce physiological mechanisms to adapt to the new environment. However, the effects of combined NaCl and NaHCO3 stress on the seedlings of Acer species are understudied. In this study, we designed an experiment to measure physiological characteristics by establishing a range of NaCl and NaHCO3 concentrations (0, 25, 50, 75, and 100 mmol L-1) to estimate the compound salt tolerance of Acer ginnala and Acer palmatum. When the concentrations of NaCl and NaHCO3 were 25 mmol L-1, the leaf water content, relative conductivity, malondialdehyde (MDA) content, proline content, soluble sugar content, and chlorophyll did not change (p > 0.05) in two maple seedlings. At concentrations greater than 50 mmol L-1, the relative conductivity and MDA content increased, proline and soluble sugars accumulated, and the potential activity of PS II (Fv/Fo), potential photochemical efficiency of PS II (Fv/Fm), PS II actual photochemical efficiency (Yield), and photosynthetic electron transfer efficiency (ETR) decreased (p < 0.05). The superoxide dismutase (SOD) and catalase (CAT) activities showed the same trend of first increasing and then decreasing (p < 0.05). The peroxidase (POD) activity increased only when concentrations of NaCl and NaHCO3 were 100 mmol L-1, while there was no statistical difference between the other treatments and the control. Therefore, the two maple seedlings adjusted their osmotic balance and alleviated oxidative stress by accumulating proline, soluble sugars and increasing CAT and SOD activities. Further analysis showed that both species are salt tolerant and the salt tolerance of Acer ginnala is better than that of Acer palmatum.

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).

Association Between Macrophage Migration Inhibitory Factor -173 G>C Gene Polymorphism and Childhood Idiopathic Nephrotic Syndrome: A Meta-Analysis.

Background: Studies have identified that MIF -173 G>C gene polymorphism is associated with idiopathic nephrotic syndrome (INS) susceptibility and steroid resistance, but the results remain inconclusive. Methods: We searched PubMed, Embase, and Web of Science for relevant studies published before 31 March 2021. Pooled data were reported as odds ratio (OR) with 95% confidence interval (CI). Noteworthiness of significant OR was estimated by the false positive report probability (FPRP) test. Trial sequential analysis (TSA) was used to control type I and type II errors. Results: We selected seven case-control studies that included 1,026 INS children (362 were steroid-resistant NS and 564 were steroid-sensitive NS) and 870 controls. The results showed that MIF -173 G>C polymorphism was significantly associated with INS susceptibility in allelic, heterozygous and dominant genetic models (C vs. G: OR = 1.325, 95% CI: 1.011-1.738; GC vs. GG: OR = 1.540, 95% CI: 1.249-1.899; CC + GC vs. GG: OR = 1.507, 95% CI: 1.231-1.845), and FPRP test and TSA indicated that the associations were true in heterozygous and dominant models. The pooled results also revealed that MIF -173 G>C polymorphism was significantly associated with steroid resistance in allelic, homozygous and recessive models (C vs. G: OR = 1.707, 95% CI: 1.013-2.876; CC vs. GG: OR = 4.789, 95% CI: 2.109-10.877; CC vs. GC + GG: OR = 4.188, 95% CI: 1.831-9.578), but FPRP test indicated that all these associations were not noteworthy. Furthermore, TSA revealed that the non-significant associations between MIF -173 G>C polymorphism and steroid resistance in heterozygous and dominant models were potential false negative. Conclusions: This meta-analysis could draw a firm conclusion that MIF -173 G>C polymorphism was significantly associated with increased INS risk in heterozygous and dominant genetic models. MIF -173 G>C polymorphism was not likely to affect steroid responsiveness, but more studies were needed to confirm.

A Single-Center, Cross-Sectional Study of Children with Steroid-Resistant Nephrotic Syndrome in Southern China.

INTRODUCTION: We conducted a cross-sectional study on children with steroid-resistant nephrotic syndrome (SRNS) in a single center in Southern China. METHODS: A total of 166 SRNS cases in the Paediatric Nephrology Center of the First Affiliated Hospital of Sun Yat-Sen University from September 1, 2006, to August 31, 2016 were retrospectively analysed. The inclusion criteria were: 1) age ≤ 14 years, 2) diagnosed with SRNS, and 3) without purpura nephritis, immunoglobulin A nephropathy, lupus nephritis, or another secondary nephritis. Incidences of primary/ late steroid-resistance and curative effects were analysed. RESULTS: The median follow-up time was 4.64 (2.64 to 8.11) years. There were 67 cases of complete remission (CR) (40.36%), 46 cases of partial remission (PR) (27.71%), 31 cases of no remission (NR) (18.67%), 18 cases of end-stage renal disease (ESRD, 10.84%, including 7 cases of kidney transplantation), and 4 cases of death due to hematoma and severe infection after renal biopsy; renal failure after progression to ESRD; sepsis during glucocorticoid (GC) + Cyclosporine A (CsA) treatment; and multiple organ failure at the onset of disease, respectively. For the 8 cases with gene mutation, unnecessary drug treatment should be reduced due to their low responsiveness to immunosuppressive treatment. Female, patients with hematuria, primary steroid-resistance (PSR) type and histopathologic focal segmental glomerulosclerosis (FSGS) were more likely to have higher ESRD rate. Subgroup analysis of ESRD suggested that female patients and patients with PSR type were more likely to develop ESRD. Cox-regression analysis showed that female (HR = 3.04, 95% CI: 1.18 to 7.86; P < .05), without hematuria (HR = 0.36, 95% CI: 0.14 to 0.91; P < .05), and LSR type (HR = 0.17, 95% CI: 0.04 to 0.74; P < .05) were significantly associated with ESRD. Kaplan-Meier survival analysis also showed the same trends. CONCLUSION: Of the 166 SRNS cases, 68.07% of patients achieved CR or PR, 18.67% of cases had NR, 10.84% of cases developed ESRD, and 2.41% of patients died during follow-up. Female gender, hematuria, and PSR type were positively associated with ESRD.

Clinicopathological Analysis of 34 Cases of Primary Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in Chinese Children.

Background: This study aimed to summarize the clinicopathological features and prognostic risk factors of primary antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in children. Methods: Clinical and prognostic data for children admitted to our center with AAV between September 2003 and September 2020 were studied retrospectively. The incidence and risk factors of end-stage renal disease (ESRD) were calculated and analyzed. Results: Thirty-four children were enrolled; 28 were female, with a median onset age of 10 years. Except for one case negative for ANCA, the other 33 patients were diagnosed with microscopic polyangiitis (MPA). The most frequently involved organ was the kidney (100.0%), followed by the lungs (58.8%) and heart (50.0%). Twenty children (58.8%) progressed to ESRD with a median course of 3 months, and they were more likely to present respiratory and cardiovascular system involvement than were the non-ESRD group (P < 0.05). Patients in the ESRD group also had a higher serum creatinine level, 24-h protein excretion, Pediatric Vasculitis Activity Score (PVAS), and a lower level of estimated glomerular filtration rate (eGFR), hemoglobin, and complement C3 than had those in the non-ESRD group (P < 0.05). The main pathological manifestations were crescentic and sclerotic classes in the ESRD group and focal class in the non-ESRD group. After 6 months of induction therapy, 90.0% of cases achieved complete or partial remission. The multivariate logistic regression model showed that baseline eGFR < 60 ml/min/1.73 m2 was an independent risk factor for progressing to ESRD (OR = 0.016, 95% CI = 0.001~0.412, P = 0.012). Conclusions: AAV in children usually occurs in teenage girls, and the most commonly involved organ is the kidney, of which hematuria is the most common symptom, followed by proteinuria, abnormal renal function (eGFR < 90 ml/min/1.73 m2), etc. The primary type of AAV is MPA. Nearly 60% of patients progressed to ESRD with a median course of 3 months. Baseline eGFR < 60 ml/min/1.73 m2 is an independent risk factor for ESRD progression in AAV children.

Long-Term Outcome of Secondary Steroid-Resistant Nephrotic Syndrome in Chinese Children.

INTRODUCTION: Secondary steroid-resistant nephrotic syndrome (SRNS) refers to the condition when patients with initial steroid-sensitive nephrotic syndrome develop steroid resistance in subsequent relapses. Long-term outcomes of secondary SRNS in children are uncertain. METHODS: This was a single-center retrospective study of 56 children with secondary SRNS between 2006 and 2016. The survival curve was estimated using the Kaplan-Meier method. Independent risk factors for end-stage renal disease (ESRD) were determined using Cox proportional hazards model. RESULTS: The median time from nephrotic syndrome onset to secondary SRNS was 7.8 months. Biopsy results at diagnosis secondary SRNS showed that 64.3% of cases were minimal change disease (MCD). No remission was observed in seven (12.5%) patients within the first year. The mean follow-up time was 7.8 ± 3.2 years. Eight patients were clinically cured, one died before ESRD, 10 reached ESRD, and 75.0% (3 of 4) of patients recurred post-transplantation. The 10-year ESRD-free survival rate was 85.8%. No response to intensified immunosuppression (IIS) in the first year was the independent predictor for ESRD. Repeat biopsies were performed in 20 cases, revealing that the reclassification from MCD to mesangial hypercellularity and focal segmental glomerulosclerosis (FSGS) in two when secondary steroid resistance appeared, from MCD and mesangial hypercellularity to FSGS in seven who developed multidrug resistance, and from FSGS to MCD and mesangial hypercellularity in two with favorable outcomes. CONCLUSIONS: The long-term outcome in children with secondary SRNS was heterogeneous, and no response to IIS in the first year was the independent predictor for ESRD. In patients with repeat biopsy, changes in histological appearance to FSGS were associated with multidrug resistance.

Genetic Variations and Clinical Features of NPHS1-Related Nephrotic Syndrome in Chinese Children: A Multicenter, Retrospective Study.

Introduction: Few studies have addressed the genetic spectrum of NPHS1 variants in Chinese children with nephrotic syndrome. In this multicenter study, the clinical manifestations and features of NPHS1 variants in Chinese children with nephrotic syndrome were researched. Method: Genotypical and phenotypical data from 30 children affected by NPHS1 variants were collected from a multicenter registration system in China and analyzed retrospectively. Results: The patients were divided into two groups: congenital nephrotic syndrome (CNS [n = 24]) and non-CNS (early onset nephrotic syndrome [n = 6]). Renal biopsy was performed on four patients in the non-CNS group, revealing minimal change disease in three and focal segmental glomerulosclerosis in one. A total of 61 NPHS1 variants were detected, involving 25 novel variants. The "recurrent variants" included c.928G>A(p.Asp310Asn) in eight patients with CNS, followed by c.616C>A(p.Pro206Thr) in four, and c.2207T>C (p.Val736Ala) in three. Steroid treatment was applied in 29.2% (7/24)of the patients in the CNS group and 50% (3/6) of the patients in the non-CNS group. One patient in each group experienced complete remission but relapsed subsequently. Immunosuppressants were administered to three patients in the non-CNS group, eliciting an effective response. In the CNS group, three patients underwent renal transplantation and six died mainly from infection. Conclusion: Variants of NPHS1 cause CNS and early childhood-onset nephrotic syndrome. NPHS1 variants in Chinese individuals with nephrotic syndrome (NS) were mainly compound heterozygous variants, and c.928G>A(p.Asp310Asn) in exon 8 may act as a recurrent variant in the Chinese population, followed by c.616C>A(p.Pro206Thr) in exon 6. Steroids and immunosuppressants may be effective in selected patients.

Responsible genes in children with primary vesicoureteral reflux: findings from the Chinese Children Genetic Kidney Disease Database.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Analysis of 10 Pediatric Nephrotic Syndrome Cases With Complications of Cerebral Sinovenous Thrombosis.

Background: To analyze the clinical characteristics of nephrotic syndrome (NS) with complications of cerebral sinovenous thrombosis (CSVT) in children. Method: Clinical, radiographic, laboratory, and treatment data obtained from 10 confirmed cases of NS with complications of CSVT were analyzed. All patients were followed up for at least 18 months. CSVT was diagnosed by cerebral computed tomography (CT) and/or magnetic resonance imaging (MRI) with or without magnetic resonance venography (MRV) of the cerebral vessels. Results: Among 10 cases reported, 4 were steroid-sensitive NS with frequent relapse, 5 were steroid-resistant (three of them had renal biopsies showing two minimal change disease and one IgA nephropathy), and 1 was steroid-sensitive with one relapse. Common clinical manifestations were headache or ophthalmodynia complicated by vomiting, dizziness, convulsion, and coma. Neuropathologic signs were positive in some cases. Papilledema appeared in only one case with winding of vein. Cerebrospinal fluid was examined in three cases with elevated pressure but normal cytological and biochemical results. D dimer and fibrinogen levels were elevated while prothrombin time and activated partial thromboplastin time were shortened. Five out of seven cases who had performed cranial CT were suspicious for cerebral thrombosis. Nine cases had cranial MRI with abnormal signs in seven cases. All of the cases received MRV, confirming the diagnosis of CVST. Conclusion: Clinical manifestations of NS with CSVT are not specific but varied. Therefore, CSVT should be considered once nervous manifestations present. MRV is a better method in the diagnosis of CSVT.