A study to evaluate the pattern, causality, predictability, and severity of adverse drug reactions to corticosteroid therapy in pediatric idiopathic nephrotic syndrome at a tertiary care center

Background: Adverse drug reactions (ADRs) in children cannot be predicted based on those observed in adults. Systematic surveillance of ADRs in children, in particular to corticosteroids are limited. Aim and Objective: The aim of the study was to evaluate the pattern as well as causality, preventability, and severity of occurrence of ADRs due to corticosteroid therapy in pediatric idiopathic nephrotic syndrome (INS). Materials and Methods: After obtaining approval from Institutional Ethics Committee and informed consent/assent, 98 patients who developed ADRs were included in the study. Each patient’s demographic, clinical, treatment data, response pattern, and ADRs to corticosteroids as per Indian Academy of Pediatrics guidelines were noted in the pro forma. The data were analyzed using descriptive statistics. Results: Total of 148 ADRs were observed due to corticosteroids among 98 patients diagnosed with nephrotic syndrome. The most common ADR was cushingoid features (18%), followed by infections (14%), gastrointestinal symptoms (11.48%), hypocalcemia (8%), and growth retardation (7%). About 45% of the ADRs were of “possible” causality and 32% were certain. Severity assessment indicates 54% as mild and majority of ADRs were not preventable. Conclusions: This study provides data of ADRs to corticosteroid therapy in INS patients. Most of the ADRs were predictable and possibly preventable and mild, which highlights the importance of early detection and management of ADR.

Renal biopsy in children with nephrotic syndrome: a study of histopathological pattern

Background: Idiopathic nephrotic syndrome (INS) is a common childhood renal disease characterized by a remitting and relapsing course, associated with different histopathological subtypes. The true incidence of various histopathological subtypes of NS remains under estimated owing to the diversity in indication criteria for performing renal biopsies in pediatric population.Methods: This was a cross-sectional observational study in children with nephrotic syndrome at a tertiary health care centre. Total 22 children, with nephrotic syndrome, who underwent renal biopsy procedure during a period of one year, were enrolled for the study. Indications of renal biopsy were noted, and the histopathology reports were studied in detail.Results: In this study group, the most common indication for renal biopsy was 'Atypical age (> 8years) of diagnosis in 45.5% (10/22) patients, followed by 22.7% (5/22) in 'Children presenting with hypertension and hematuria'.The most common histopathological finding in these children was mesangial proliferative glomerulonephritis in 45.5% (10/22) patients followed by IgA nephropathy with mesangial proliferation in 22.72% (5/22) and minimal change disease in only 13.6% (3/22).Conclusions: This study highlights the occurrence of non-MCD as the common cause of INS in the children and denotes the significance of performing renal biopsies in children with INS for better prognostication.

Expressions of Toll like receptor-2,-4 ,-6 in peripheral blood mononuclear cells and the association of serum IgG and IgM levels in children with idiopathic nephrotic syndrome / 中华实用儿科临床杂志

Objective To investigate expressions of Toll-like receptor (TLR)-2,TLR-4 and TLR-6 in peripheral blood mononuclear cells (PBMC) and serum immunoglobulin G (IgG) and IgM levels in pediatric idiopathic nephrotic syndrome (INS).The correlation between Toll-like receptors (TLR-2,TLR-4 and TLR-6) and serum immunoglobulin levels (IgG and IgM) will be proven in the pathogenesis of childhood INS in active stage (AS) and remission stage (RS).Methods Forty-two INS patients (experimental group,32 boys,10 girls) and 29 healthy individuals (healthy control group,19 boys,10 girls) were enrolled in the present study from June,2017 to October,2018 in the First Affiliated Hospital of Xinxiang Medical University.There were no significant differences in gender (x2 =0.966,P =0.326) and age (t =-0.139,P =0.89) between 2 groups.TLR-2 mRNA,TLR-4 mRNA and TLR-6 mRNA expressions of PBMC were evaluated by using real-time PCR in both INS children with AS and RS and healthy children.The blood samples were drawn to detect by way of immunoturbidimetry serum immunoglobulin (IgG and IgM) levels in both INS children with AS and healthy children.The correlation between Toll-like receptors (TLR-2 mRNA,TLR-4 mRNA,TLR-6 mRNA) and serum immunoglobulin (IgG,IgM) levels were analyzed by using spearman correlation analysis.Results The expression levels of TLR-2 mRNA in INS children with AS,RS and healthy children were 1.85 ± 0.30,1.00 ± 0.23 and 0.85 ± 0.12,respectively,and the expression levels of TLR-4 mRNA were 1.24 ± 0.27,0.80 ± 0.23 and 0.68 ± 0.09,respectively,while the expression levels of TLR-6 mRNA were 1.35 ± 0.23,0.92 ± 0.19 and 0.79 ± 0.15,respectively,so the differences were statistically significant (F =198.453,67.013,82.405,all P ＜ 0.01).The serum IgG level(2.90 ± 0.89) g/L was lower in INS children with AS compared with the controls (9.21 ± 1.88) g/L.However,the serum IgM level (2.87 ± 0.96) g/L was higher in INS children with AS when compared with the controls(1.48 ± 0.30),and the differences were statistically significant(t =-16.810,8.701,all P ＜0.05).No significant correlation was noted between Toll-like receptors (TLR-2 mRNA,TLR-4 mRNA,TLR-6 mRNA) and serum immunoglobulin levels (IgG,IgM) (all P ＞ 0.05).Conclusions The results indicate that Toll-like receptors (TLR-2,TLR-4 and TLR-6) and immunoglobulin (IgG,IgM) might play a role in the pathogenesis of pediatric INS via distinct pathway.

Expression levels and clinical value of urinary exosomal miR-194-5p in children with idiopathic nephrotic syndrome / 临床检验杂志

Objective@#To investigate the levels of urinary exosomal miR-194-5p in children with idiopathic nephrotic syndrome (INS) and its clinical value as a non-invasive auxiliary diagnostic marker. @*Methods@#Urine samples were collected from 101 INS children and 98 sex- and age-matched healthy children, and the levels of urinary exosomal miR-194-5p were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The clinical value of urinary exosomal miR-194-5p in the diagnosis of children′s INS was evaluated by the ROC curve and correlation analysis. @*Results@#The levels of urinary exosomal miR-194-5p in INS children (2.420 [0.650,9.515] fmol/L) were significantly higher than that in healthy controls (0.360 [0.220,0.653] fmol/L, U=1 552, P＜0.01). Compared with the INS children before treatment, the levels of urinary exosomal miR-194-5p in clinical remission period decreased significantly (0.320 [0.145,0.523] fmol/L vs 0.975 [0.375,4.358] fmol/L, W=708, P＜0.01). Moreover, the levels of miR-194-5p in INS children with heavy urine protein (8.430 [7.225,13.070] fmol/L) were significantly higher than that with light urine protein (2.130 [1.180,3.090] fmol/L, U=0, P＜0.01). The area under the ROC curve (AUC ROC ) of miR-194-5p was 0.843 (95%CI: 0.789-0.897) for the diagnosis of INS children. Spearman correlation analysis showed that the levels of urinary exosomal miR-194-5p in INS children were negatively correlated with serum albumin levels (r=-0.300), and were positively correlated with serum total cholesterol levels (r=0.278) and 24-hour urine protein content (r=0.296, all P＜0.01). @*Conclusion@#The levels of urinary exosomal miR-194-5p in INS children increase obviously, and are closely associated with 24-hour urine protein, serum albumin and total cholesterol levels, indicating that urinary exosomal miR-194-5p may be serve as a new non-invasive fluid biopsy molecular marker for the auxiliary diagnosis of INS in children.

Expressions of Toll like receptor-2, -4 , -6 in peripheral blood mononuclear cells and the association of serum IgG and IgM levels in children with idiopathic nephrotic syndrome / 中华实用儿科临床杂志

Objective@#To investigate expressions of Toll-like receptor(TLR)-2, TLR-4 and TLR-6 in peripheral blood mononuclear cells (PBMC) and serum immunoglobulin G (IgG) and IgM levels in pediatric idiopathic nephrotic syndrome (INS). The correlation between Toll-like receptors (TLR-2, TLR-4 and TLR-6) and serum immunoglobulin levels (IgG and IgM) will be proven in the pathogenesis of childhood INS in active stage (AS) and remission stage (RS).@*Methods@#Forty-two INS patients (experimental group, 32 boys, 10 girls) and 29 healthy individuals (healthy control group, 19 boys, 10 girls) were enrolled in the present study from June, 2017 to October, 2018 in the First Affiliated Hospital of Xinxiang Medical University. There were no significant differences in gender (χ2=0.966, P=0.326) and age (t=-0.139, P=0.89) between 2 groups.TLR-2 mRNA, TLR-4 mRNA and TLR-6 mRNA expressions of PBMC were evaluated by using real-time PCR in both INS children with AS and RS and healthy children.The blood samples were drawn to detect by way of immunoturbidimetry serum immunoglobulin (IgG and IgM) levels in both INS children with AS and healthy children.The correlation between Toll-like receptors (TLR-2 mRNA, TLR-4 mRNA, TLR-6 mRNA) and serum immunoglobulin (IgG, IgM) levels were analyzed by using spearman correlation analysis.@*Results@#The expression levels of TLR-2 mRNA in INS children with AS, RS and healthy children were 1.85±0.30, 1.00±0.23 and 0.85±0.12, respectively, and the expression levels of TLR-4 mRNA were 1.24±0.27, 0.80±0.23 and 0.68±0.09, respectively, while the expression levels of TLR-6 mRNA were 1.35±0.23, 0.92±0.19 and 0.79±0.15, respectively, so the differences were statistically significant(F=198.453, 67.013, 82.405, all P<0.01). The serum IgG level(2.90±0.89) g/L was lower in INS children with AS compared with the controls(9.21±1.88) g/L.However, the serum IgM level (2.87±0.96) g/L was higher in INS children with AS when compared with the controls(1.48±0.30), and the differences were statistically significant(t=-16.810, 8.701, all P<0.05). No significant correlation was noted between Toll-like receptors(TLR-2 mRNA, TLR-4 mRNA, TLR-6 mRNA) and serum immunoglobulin levels (IgG, IgM) (all P>0.05).@*Conclusions@#The results indicate that Toll-like receptors (TLR-2, TLR-4 and TLR-6) and immunoglobulin (IgG, IgM) might play a role in the pathogenesis of pediatric INS via distinct pathway.

T-lymphocyte-expressing inflammatory cytokines underlie persistence of proteinuria in children with idiopathic nephrotic syndrome / Os linfócitos T que expressam citocinas inflamatórias são subjacentes à persistência de proteinúria em crianças com síndrome nefrótica idiopática

Abstract Objective: There is evidence of an important role of immune system changes in the triggering and maintenance of idiopathic nephrotic syndrome (INS). The aim of this study was to investigate the expression of cytokines in lymphocyte populations of patients with INS in comparison to healthy individuals, according to proteinuria. Methods: This cross-sectional study included 44 patients with INS and eight healthy children, matched for age and sex (controls). Patients were subdivided according to proteinuria: persistent proteinuria or partial remission (PP ≥ 300 mg/24 h, n = 17) and low proteinuria or complete remission (LP < 300 mg/24 h, n = 27). Ex vivo analysis of peripheral blood leukocytes by flow cytometry was performed using surface markers for T-lymphocytes, TCD4, TCD8, natural killer (NK) cells, NKT, and B-lymphocytes. Frequencies of intracellular cytokines were analyzed in these cells. Results: The frequencies of B-lymphocytes, NK cells, and NKT cells were lower in INS than in controls, whereas INS patients had a higher frequency of CD4+tumor necrosis factor (TNF)-α+ cells than controls. Cytotoxic-T-lymphocytes expressing IFN-γ were lower in INS than in controls. Patients with PP showed higher frequencies of CD4-T-lymphocytes expressing IFN-γ and TNF-α than controls. CD8-lymphocytes expressing TNF-α were increased in PP group when compared with LP and controls, while CD8+interferon (IFN)-γ+ cells were lower than in LP and in controls. Conclusion: Regardless the level of proteinuria, INS patients had increased expression of TNF-α in CD4-lymphocytes and reduced expression of IFN-γ in CD8-lymphocytes. Persistence of proteinuria was associated with higher levels of inflammatory markers.

Resumo Objetivo Há comprovação do importante papel das alterações no sistema imunológico no desencadeamento e manutenção da síndrome nefrótica idiopática (SNI). O objetivo deste estudo foi investigar a expressão das citocinas em populações de linfócitos de pacientes com SNI em comparação a indivíduos saudáveis e de acordo com a proteinúria. Métodos Este estudo transversal incluiu 44 pacientes com SNI e oito crianças saudáveis, pareados por idade e sexo (controles). Os pacientes foram subdivididos de acordo com a proteinúria: proteinúria persistente ou remissão parcial (PP ≥ 300 mg/24 h, n = 17) e proteinúria baixa ou remissão completa (PB < 300 mg/24 h, n = 27). A análise ex vivo de leucócitos no sangue periférico por citometria de fluxo foi feita utilizando marcadores de superfície para linfócitos T, TCD4, TCD8, células natural killer (NK), linfócitos NKT e B. As frequências das citocinas intracelulares foram analisadas nessas células. Resultados A frequência dos linfócitos B, células NK e células NKT foi menor em pacientes com SNI do que nos controles, ao passo que os pacientes com SNI apresentaram maior frequência de células CD4+fator de necrose tumoral (TNF)-α+ do que nos controles. Os linfócitos T citotóxicos que expressam interferon (IFN)-γ foram menores nos pacientes com SNI do que nos controles. Os pacientes com PP mostraram maiores frequências de linfócitos T CD4 que expressam IFN-γ e TNF-α que os controles. Os linfócitos CD8 que expressam TNF-α apresentaram aumento no grupo com PP, em comparação aos com PB e os controles, apesar de as células CD8+IFN-γ+ serem mais baixas nos pacientes com PB e nos controles. Conclusão Com relação ao nível de proteinúria, os pacientes com SNI apresentaram aumento na expressão de TNF-α nos linfócitos CD4 e expressão reduzida de IFN-γ nos linfócitos CD8. A persistência da proteinúria foi associada a maiores níveis de marcadores inflamatórios.

Expressions of Toll like receptor-1,-3,-9 in peripheral blood mononuclear cells of children with idiopathic nephrotic syndrome / 中华实用儿科临床杂志

Objective To investigate the expressions of Toll-like receptor (TLR)-1,TLR-3,TLR-9 in peripheral blood mononuclear cells (PBMC) of children with idiopathic nephrotic syndrome (INS).Methods The expressions of TLR-1,TLR-3 and TLR-9 mRNA were measured by real time-polymerase chain reaction (RT-PCR) in PBMC of 45 children with INS came from the First Affiliated Hospital of Xinxiang Medical University before and after treatment (active group and remission group,respectively) and 30 healthy children from medical examination center as healthy control group,so as to explore the relativity between TLR-1,TLR-3 and TLR-9 mRNA and serum levels of albumin and cholesterol.Results The expression of TLR-1 mRNA/β-actin in PBMC of children with INS before treatment (the active group) was significantly higher than that in the remission group (2.432 ± 0.231 vs.1.675 ± 0.627,t =7.599,P ＜ 0.05) and the healthy control group (2.432 ± 0.231 vs.0.512 ± 0.228,t =35.446,P ＜0.05),and the differences were statistically significant in the expression of TLR-1 mRNA/β-actin between remission group and healthy control group (1.675 ± 0.627 vs.0.512 ± 0.228,t =9.722,P ＜ 0.05).The expression of TLR-3 mRNA/β-actin in PBMC of children with INS before treatment (the active group) (0.987 ± 0.124) was significantly higher than that in the remission group (0.501 ± 0.016) and the healthy control group (0.021 ± 0.001),the differences were statistically significant (t =26.076,42.571,all P ＜ 0.05),and the remission group was significantly higher than that in healthy control group (t =163.732,P ＜ 0.05).The expression of TLR-9 mRNA/β-actin in PBMC of children with INS before treatment (activity group) (1.965 ±0.952) was significantly higher than that in the remission group (1.336 ±0.282) and the healthy control group (0.790 ±0.731),the differences were statistically significant (t =4.249,5.734,all P ＜ 0.05),and the remission group was significantly higher than that in healthy control group (t =4.541,P ＜ 0.05).The serum levels of albumin in children with INS before treatment (activity group) (23.62 ± 11.67) g/L was significantly lower than that in remission group (42.19 ± 16.33) g/L and healthy control group (46.88 ± 14.80) g/L,and the differences were statistically significant (t =-6.20,-7.58,all P ＜0.01).The serum levels of cholesterol in children with INS before treatment (the active group) (9.54 ±2.53) mmol/L was significantly higher than that in the remission group (3.01 ± 1.72) mmoL/L and the healthy control group (2.89 ± 1.66) mmol/L,and the differences were statistically significant (t =14.32,12.677,all P ＜ 0.01).The serum levels of albumin and cholesterol in children with INS after treatment were not statistically significant difference compared to the healthy control group (t =-1.264,0.30,all P ＞ 0.05).The correlation analysis showed that there was a negative correlation between the expressions of TLR-1,TLR-3 and TLR-9 mRNA and the serum level of albumin in PBMC of children with INS before treatment (r =-0.457,-0.891,-0.125,respectively,all P ＜ 0.05).However,there was a positive correlation between the expressions of TLR-1,TLR-3 and TLR-9 mRNA and the serum level of cholesterol (r =0.445,0.911,0.872,all P ＜ 0.05).Conclusions The expressions of TLR-1,TLR-3 and TLR-9 mRNA in PBMC of children with INS were significantly higher and correlated with activity of disease.

Differentially methylated genes in children with steroid-dependent or steroid-sensitive nephrotic syndrome:A bioinformatic analysis / 医学研究生学报

Objective Few researches have been reported on the gene methylation in children with steroid-sensitive nephrot-ic syndrome (SSNS) or steroid-dependent nephrotic syndrome (SDNS).This study aimed to investigate the possible pathogenesis and therapeutic target of SSNS and SDNS by screening differentially methylated genes ( DMGs) and bioinformatic analysis using DNA meth-ylation microarray. Methods This study included 3 hospitalized children with SSNS and another 4 with SDNS, all treated with full dose of prednisone ( 2 mg per kilogram of the body weight per day or 60 mg per m2 per day).Negative urine protein was achieved within 4 weeks in the former group , while the latter , though sensitive to hor-monal therapy , relapsed within 2 weeks after drug withdrawal or dose reduction .DNA was extracted from the peripheral blood of the patients in both groups for screening DMGs and bioinformatic analysis using DNA methylation microarray . Results Compared with the patients with SSNS, 318 DMGs were found in the SDNS group , among which 193 were hypermethylated and the other 125 hypomethylated .These abnormal genes were mainly located in the open reading frame of DNA and the CpG island region .DMGs were mainly involved in Rho guanyl-nucleotide exchange factor activity , nucleoside-triphosphatase regulator activity , GTPase activator activity , and other molecular functions .The biological processes were chiefly associ-ated with the regulation of the generation of precursor metabolites and energy , antigen processing and presentation , regulation of Rho and Ras protein signal transduction , lamellipodium assembly , regeneration , and other biological processes .The cell composition was mainly related to MHC protein complexes , perichromatin fibrils , and the MHC class I protein complex .Analysis of the KEGG signaling pathway showed that DMGs participated in 9 signaling pathways , involving type I diabetes , starch and sucrose metabolism , allograft re-jection, autoimmune thyroid disease , and others. Conclusion The heterogeneity of methylation is widespread in children with SDNS and may be one of the causes of steroid dependence , which has provided a basis for searching for potential therapeutic targets .

Study progress of Tacrolimus treatment on steroid-resistant nephrotic syndrome in children / 中华实用儿科临床杂志

Steroid-resistant nephrotic syndrome (SRNS) is a relatively difficult clinical type of treatment.The major therapy measures in present include steroid and immunosuppressant.Commonly used immunosuppressant include tacrolimus,cyclosporin,cyclophosphamide,mycophenolate mofetil,ect.Tacrolimus-induced clinical remission rate is superior to other immunosuppressive agents,has been the first-line agent of SRNS.Because of the individual difference in metabolism,the drug concentration of tacrolimus should be determined periodically.In order to obtain optimal efficacy of tacrolimus and reduce renal toxicity,the treatment protocols of small doses with long courses for children with SRNS were recommended.

A unified pathogenesis for kidney diseases, including genetic diseases and cancers, by the protein-homeostasis-system hypothesis

Every cell of an organism is separated and protected by a cell membrane. It is proposed that harmony between intercellular communication and the health of an organism is controlled by a system, designated the protein-homeostasis-system (PHS). Kidneys consist of a variety of types of renal cells, each with its own characteristic cell-receptor interactions and producing characteristic proteins. A functional union of these renal cells can be determined by various renal function tests, and harmonious intercellular communication is essential for the healthy state of the host. Injury to a kind of renal cells can impair renal function and induce an imbalance in total body health. Every acute or chronic renal disease has unknown etiologic substances that are responsible for renal cell injury at the molecular level. The immune/repair system of the host should control the etiologic substances acting against renal cells; if this system fails, the disease progresses to end stage renal disease. Each renal disease has its characteristic pathologic lesions where immune cells and immune proteins, such as immunoglobulins and complements, are infiltrated. These immune cells and immune proteins may control the etiologic substances involved in renal pathologic lesions. Also, genetic renal diseases and cancers may originate from a protein deficiency or malfunctioning protein under the PHS. A unified pathogenesis for renal diseases, including acute glomerulonephritis, idiopathic nephrotic syndrome, immunoglobulin A nephropathy, genetic renal diseases such as Alport syndrome, and malignancies such as Wilms tumor and renal cell carcinoma, is proposed using the PHS hypothesis.

The mechanisms of steroid resistance of children′s idiopathic nephrotic syndrome / 国际儿科学杂志

The resistance to steroid remains a major trouble in the treatment of idiopathic nephrotic syn-drome,and the mechanisms are complicated. Recent studys have shown that multidrug resistance gene l and P-glycoprotein170,glucocorticoid receptor,renal pathology,gene mutation and complications are all closely related to the resistance to steroid. This review is focused on the mechanisms of steroid resistance of children′s idiopath-ic nephrotic syndrome.

Clinical Features and Long-Term outcomes of Patients with Late Steroid Resistant/Sensitive Nephrotic Syndrome: A Single Center Study

OBJECTIVE: To find out clinical features and long-term outcomes of idiopathic childhood nephrotic syndrome(NS) patients with late steroid resistance(LSR)/late steroid sensitiveness(LSS). PATIENTS AND METHODS: A retrospective chart review was performed on 480 patients diagnosed with idiopathic childhood NS at Asan Medical Center Children's Hospital from 1990 to 2013. Twenty-four patients whose responsiveness to steroids changed over a minimum 2 year follow-up period (2-17.5 years) were investigated. All patients had undergone a renal biopsy. RESULTS: Among 480 nephrotic children, 428 (89%) were sensitive to the first steroid course. Of those who initially responded, 11 (2.5%) developed resistance to steroid therapy after relapses. LSR mostly developed between 1 month and 1 year after the initial episode. Six patients showed a minimal change and five showed focal segmental glomerulosclerosis (FSGS). Nine (82%) responded to cyclosporine or methylprednisolone pulse therapy. Of these, two had no further relapse, whereas the other seven experienced several relapses that ranged in length from 1.1 to 13.9 years. Three of the nine who initially responded to immunosuppression went on to experience several changes in steroid responsiveness. Two (18%) with resistance to immunosuppressants, including steroids, eventually progressed to end stage renal disease. Among the 52 patients (11%) who were initially steroid resistant, 13 (23%) were converted to steroid sensitive at relapses. Among these, 9 showed minimal change and 4 showed FSGS. Two had no further relapse and the other 11 responded to steroids on subsequent relapses ranging in length from 1.3 to 9.4 years. All these patients have had no further changes in steroid responsiveness with normal renal function. CONCLUSIONS: In this study, 2.5% of initial steroid responders and 25% of initial steroid non-responders changed their responsiveness to steroids at subsequent relapses. Eighteen percent of LSR patients developed end stage renal disease. All of the LSS patients showed preserved normal renal function. Responsiveness to immunosuppressants seemed to be the most important factor determining longterm outcomes in LSR/LSS patients.

Tratamiento del síndrome nefrótico idiopático en niños / Treatment of idiopathic nephrotic syndrome in children

La incidencia anual del síndrome nefrótico se ha estimado en 1-3 por cada 100,000 niños menores de 16 años de edad. En niños, la causa más común del síndrome nefrótico es el síndrome nefrótico idiopático (SNI), que se define por la presencia de proteinuria e hipoalbuminemia y es, por definición, una enfermedad primaria. En el estudio de la biopsia renal se pueden encontrar alteraciones histológicas renales no específicas que incluyen lesiones mínimas, glomeruloesclerosis segmentaria y focal y proliferación mesangial difusa. En todos los pacientes con SNI se indica el tratamiento con corticosteroides, ya que, habitualmente, no se requiere de una biopsia renal antes de iniciar el tratamiento. La mayoría de los pacientes (80-90%) responden a este tratamiento. Los niños con SNI que no presentan remisión completa con el tratamiento con corticosteroides generalmente presentan glomeruloesclerosis segmentaria y focal, y requieren tratamiento con inhibidores de calcineurina (ciclosporina o tacrolimus), mofetil micofenolato o rituximab, además del bloqueo del sistema renina-angiotensina. En este artículo se revisan las recomendaciones recientes aceptadas para el tratamiento de los niños con SNI.

The annual incidence of the nephrotic syndrome has been estimated to be 1-3 per 100,000 children < 16 year of age. In children, the most common cause of nephrotic syndrome is idiopathic nephrotic syndrome (INS). INS is defined by the presence of proteinuria and hypoalbuminemia and by definition is a primary disease. Renal biopsy study shows non-specific histological abnormalities of the kidney including minimal changes, focal and segmental glomerular sclerosis, and diffuse mesangial proliferation. Steroid therapy is applied in all cases of INS. Renal biopsy is usually not indicated before starting corticosteroid therapy. The majority of patients (80-90%) are steroid-responsive. Children with INS who do not achieve a complete remission with corticosteroid therapy commonly present focal and segmental glomerular sclerosis and require treatment with calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil or rituximab, plus renin-angiotensin system blockade. In this article we review the recent accepted recommendations for the treatment of children with INS.

Familial steroid-sensitive idiopathic nephrotic syndrome: seven cases from three families in China

OBJECTIVES: Familial steroid-sensitive idiopathic nephrotic syndrome is rare, and only approximately 3% of patients have affected siblings. METHODS: Herein, we report seven cases of patients with steroid-sensitive idiopathic nephrotic syndrome from three Chinese families. Mutational screening of the Nphs2 gene was performed in all the patients. RESULTS: All seven of the familial steroid-sensitive idiopathic nephrotic syndrome cases in our sample exhibited minimal change disease, and one case also presented with mesangial proliferative glomerulonephritis, according to the renal pathology. No significant was associations were found between Nphs2 gene mutations and the onset of proteinuria and nephrotic syndrome in these familial cases. CONCLUSIONS: The presence of minimal change disease is important, but it is not an unusual finding in patients with familial steroid-sensitive idiopathic nephrotic syndrome, which appears to be clinically benign and genetically distinct from other types of nephrosis. .

The Clinical Characteristics of Steroid Responsive Nephrotic Syndrome of Children according to the Serum Immunoglobulin E Levels and Cytokines

PURPOSE: The nephrotic syndrome (NS) is characterized by the favorable response to glucocorticoid therapy and the development of NS may be associated with dysfunctional immune systems. In order to investigate the serum immunoglobulin E (IgE) levels and cytokines activity in pediatric NS, the total of 32 steroid responsive NS patients and 5 healthy controls were enrolled in this study. MATERIALS AND METHODS: All patients were divided into two groups according to the initial serum IgE levels, such as normal and high IgE group, and their clinical characteristics were evaluated. In addition, serum levels of interleukin (IL)-4, IL-5, IL-10 and transforming growth factor (TGF)-beta were compared and correlated with serum albumin, proteinuria by means of disease severity, and cytokines. RESULTS: In the high IgE group, the higher comorbidity of allergic diseases and relapsing rate, the longer duration of steroid therapy before initial remission, and the higher serum IL-4 and IL-5 levels were found. In all patients, initially higher serum levels of IL-4 and IL-5 declined to normal levels after steroid therapy, whereas the serum IL-10 levels showed no significant difference between nephrotic phase (heavy proteinuria) and remission phase (no proteinuria) of NS. The serum TGF-beta levels of the nephrotic phase were significantly lower than those of remission phase or control group, and returned to normal control levels after steroid therapy. CONCLUSION: This study indicates that initial IgE level is associated with steroid responsiveness and disease severity, and cytokine activities may also be related to the pathogenesis of pediatric steroid responsive NS.

Predictive Clinical Factors for the Treatment Response and Relapse Rate in Childhood Idiopathic Nephrotic Syndrome

PURPOSE: This study was aimed to determine the predictive risk factors for the treatment response and relapse rate in children diagnosed with idiopathic nephrotic syndrome. METHODS: We analyzed the medical records of children who were diagnosed and treated for childhood idiopathic nephrotic syndrome from November 1991 to May 2005. Variables selected in this study were age at onset, sex, laboratory data, concomitant bacterial infections, days to remission, and interval to first relapse. RESULTS: There were 46 males and 11 females, giving a male:female ratio of 4.2:1. The age(mean+/-SD) of patients was 5.8+/-4.1 years old. Of all patients who were initially given corticosteroids, complete remission(CR) was observed in 54(94.7%). Of the 54 patients who showed CR with initial treatment, 40(70.2%) showed CR within 2 weeks and 14(24.6%) showed CR after 2 weeks. The levels of serum IgG were lower in the latter group who showed CR after 2 weeks(P=0.036). Of the 54 patients who showed CR with initial treatment, 47(82.5%) relapsed. Of these patients, 35.1% were frequent relapsers and 43.9% were infrequent relapsers. There was no significant correlation between the frequency of relapse and the following variables:sex, days to remission, and laboratory data. However, age at onset and interval to first relapse had a negative correlation with the frequency of relapse (Pearson's coefficient=-0.337, -0.433, P<0.012, P<0.01). CONCLUSION: The age at onset and the interval to first relapse were found to be predictive clinical parameters for the relapse rate, while the levels of serum IgG at initial presentation were a predictive laboratory factor for treatment response in childhood idiopathic nephrotic syndrome.

Clinical Study of the Correlation of Tumor Necrosis Factor alpha and the Proteinuria of Henoch-Schonlein Nephritis and Idiopathic Nephrotic Syndrome

PURPOSE: It is not clear that the development of glomerular injury and aggravation by tumor necrosis factor alpha (TNF-alpha) is related to intrarenal or serum concentration of TNF-alpha. So, we studied the relationship between the concentration of TNF-alpha and aggravation of glomerular damage in the Henoch-Schonlein nephritis(HSN) and idiopathic nephrotic syndrome(INS). METHODS: We collected the sera and urines of 21 patients with Henoch-Schonlein purpura(HSP) and 22 patients with INS visited Chungbuk National University hospital from March 1998 to March 2001. The concentration of TNF-alpha in the sera and urines were measured by sandwich ELISA. RESULTS: Serum TNF-alpha levels in the HSP patients with renal involvement were significantly higher than those without renal involvement(P=0.009). But urine TNF-alpha levels have no correlation with renal involvement(P=0.088). In the HSN patients, proteinuria have a significant correlation with serum TNF-alpha levels(P=0.004) but less correlation with urine TNF-alpha levels(P=0.053). Otherwise, proteinuria have no correlation with serum TNF-alpha levels(P=0.763) but have a significant correlation with urine TNF-alpha levels(P=0.007) in INS. CONCLUSION: These result suggest that the serum concentration of TNF-alpha would be important to glomerular involvement in HSP. And, it is interesting that proteinuria shows a significant relation with serum TNF-alpha levels in the HSN, but with urine TNF-alpha levels in the INS. This means the major production of TNF-alpha may be originated by extrarenal inflammation in the HSN and by intrarenal tubulo-interstitial damage due to proteinuria in the INS.

Long-term Cyclosporine A(Cypol(R)) Therapy in Children with Idiopathic Nephrotic Syndrome / 대한신장학회잡지

This multicenter collaboratory study was conducted to find out the long-term therapeutic efficacy and side effect of cyclosporine A(Cypol(R), Chong Kun Dang) on children with idiopathic nephrotic syndrome who experienced frequently relapsing(FR), steroid dependent(SD), or steroid resistant(SR) pattern. Forty-six children with SD/FR NS and 5 children with SR NS were enrolled in this study. After induction of remission(SD/FR NS) with steroid or after 4 weeks of steroid therapy(SR NS), cyclosporine A was started in a dose of 4-5mg/kg/day in two divided dose and steroid(prednisolone or equivalent dose of deflazacort) was tapered slowly. During 12 months of study period, monthly check up of physical examination and various laboratory tests including BUN, creatinine, Ccr and cyclosporine blood level were done. Out of 46 children with SD/FR NS, 28(60.9%) maintained sustained remission, 16(34.8%) showed 1 or 2 relapses during therapy and 2(4.3%) cases showed no response. At 4 weeks after therapy, values of serum protein, albumin, cholesterol, and 24 hours urinary protein excretion showed normal values. Four out of 5 children with SR NS showed complete or partial remission with cyclosporine A therapy and one child showed no response. Side reaction to cyclosporine A therapy showed hypertricosis in 14 cases, hyperuricemia in 8 cases and hypomagnesemia in 16 cases. However, other laboratory tests including CBC, liver profile, BUN, creatinine and GFR(creatinine clearance utilizing 24 hour urine) did not show any abnormalities during the 12 months of study period. We performed follow-up renal biopsy in 17 children after 12 months cyclosporine A treatment. Eight cases(47.1%) showed mild cyclosporine A nephrotoxicity like interstitial fibrosis and tubular atropy. In conclusion, present study shows that cyclosporine A(Cypol(R), Chong Kun Dang) can be used quitely effectively in maintaining remission and decreasing relapse rate on children with SD/FR or SR NS. However, because administration of cyclosporine A for 12 months is found to be associated with nephrotoxicity in a significant number of patients, we are planning further study using "smaller dosage" of cyclosporine A to reduce its nephrotoxic effect and for longer period of treatment(over 2 years).

A familial steroid-responsive nephrotic syndrome report / 中华肾脏病杂志

Objective To report a familial steroid responsive idiopathic nephrotic syndrome,describe the clinic and pathologic features of the family and screen the potential mutations of NPHS2 in the kindred. Methods Clinopathological data of the family members were collected(including patients) . The reports on familial steroid responsive idiopathic nephrotic syndrome were reviewed. The characteristics were compared between them. NPHS2 mutation was screened through DHPLC for the patients. Resutts There were two brothers with steroid responsive nephrotic syndrome in this family,and the renal pathology was minimal change disease. One of them had massive proteinuria and hypertension,whose renal biopsy showed mild mesangial proliferative nephritis. In this family,any mutation in NPHS2 gene was not found as it was reported in other populations. Conclusions The present study is the first report of familial steroid responsive idiopathic nephrotic syndrome in Chinese population. No relationship between the disease and NPHS2 gene mutation in this family is found.

Clinical Study on Idiopathic Nephrotic Syndromein Children

A clinical observation was done on 38 children with idiopathic nephrotic syndrome, who had been admitted to our pediatric department during past 3 years period, from January 1978 to September 1980. The following results were obtained: At the beginning of illness, 42% were in the age group of 3~7year, and male to female ratio was approximately 3:1 of male preponderance. During initial attack and subsequent relapses, pitting edema on extremities was noticed in all cases, followed in frequency by generalized edema in 71%, ascites and /or pleural effusion in 65.8% and GI trouble in 47.4%. Response to initial continuous steroid therapy showed complete remission(group 4) in 37.8%, partial remission(group 23) in 46% and no response(group 1) in 16.2%, Within 2 weeks after instiution of steroid therapy, both diuresis and disappearance of proteinuria were noted in 57.1%. Nephritic manifestations, eg. Hematruia, hypertension & azotemia, were seen in 21.6%, 10.8%, 24.3% respectively, and the majority of children with these manifestations showed poor response to steroid therapy. Nine out of 21 patients in whon follow-up could be done over 1 year, experienced one or more relapses, giving 43% relapse rate during the 1st year, and URI was accompanied in about half of these episodes. Percutaneous renal biopsy done on 17 patients who showed steroid dependency or no response to poor response toward steroid therapy showed the following results: Minimal change nephrotic syndrome in 8, membranous nephropathy in 3, membranoproliferative glomerulonephritis in 3, focal segmental sclerosis in 1 and focal proliferative glomerulonephritis in 2. And male to female ratio was 13:4. ?Pulse?therapy with bolus dosasge of methylprednisolone was tried on 9 patients, resulting in disappearance of relapse or significant improvement in blood chemistry & urinary finding in 5. And 2 out of 5 patients in whom immunosuppressant therapy with cytoxan was giveu due to poor response to steroid, experienced complete remission. During the same study period, secondary nephrotic syndrome was observed in 6 out of 54 patients with acute glomerulonephritis, and heavy proteinuria over 2 gm/m2/day, was seen in 6 patients with acute glomerulonephritis and 2 patients with congestive heart failure.