Nephrotic Syndrome Children Research Articles

Autoantibodies Targeting Proteasome Subunit Alpha Type 1 in Autoimmune Podocytopathies.

The antibody against proteasome subunit alpha type 1 (PSMA1) is a podocyte autoantibody in idiopathic nephrotic syndrome (INS) children identified in our previous study. The aim of this study was to explore the characteristics of INS in children and the mechanism underlying its involvement in the development of INS. The levels of serum anti-PSMA1 autoantibodies in children were detected via protein microarray and compared among different disease groups. The recombinant PSMA1 protein was injected subcutaneously and intraperitoneally into mice to observe glomerular morphology and function. The PSMA1-knockdown and PSMA1-overexpressing cell lines were constructed from mouse podocytes, and their cytoskeleton and function were analyzed. Homozygous zebrafish with psma1 knockout were observed. The levels of serum anti-PSMA1 autoantibodies were higher in INS children and varied with urinary protein. In mice immunized with PSMA1, the presence of serum anti-PSMA1 autoantibody caused albuminuria and damage to the glomerular filtration membrane. Deficiency of PSMA1 impaired the podocyte cytoskeleton and physiological function. Complete deletion of psma1 caused edema, abnormal glomerular morphology and effacement of foot processes in zebrafish. PSMA1 played an important role in the maintenance of podocyte morphology and function.

Risk Factors of Relapse in Nephrotic Syndrome

Background: Nephrotic syndrome (NS) is a kidney disease with high incidence, typically in young children. NS is a disease of relapse, and it is a major problem to manage the cases with relapse. So, it is very important to find out such children who are prone to develop relapse. Hence, this study was carried out to find out the risk factors of relapse in children with NS. Objective: To determine the risk factors of relapse in patients with nephrotic syndrome. Methods: This case-control study was conducted at the Department of Paediatric Nephrology and Department of Paediatrics, Dhaka Medical College Hospital, for 12- months following ethical approval. A total of 100 NS children (age: 2-12 years) were enrolled in this study, among them 50 were cases (NS with relapse) and 50 were controls (initial attack of NS with no relapse within one year of disease onset). After obtaining written informed consent from parents/legal guardian, a detailed history, thorough clinical examination and necessary investigations were carried out in each patient during initial episode of NS. Data analysis was done by SPSS 26.0. Results: Mean age of the cases and controls was6.11±3.01years and 6.96±3.14years, respectively (p=0.169), with an overall boys-girl ration of 1.3:1. Maximum cases (56.0%) had infrequent relapse. Lower age of onset was prevalent among case group than control (31.96±15.15 months vs 46.48±27.76 months; p=0.002). Infection was significantly more prevalent among cases than controls (68.0% vs 38.0%; OR=3.46; p=0.003), UTI (38.0% vs 10.0%; OR; 5.52; p=0.001). Cases had significantly higher history of atopy (52.0% vs 30.0%; OR=2.53; p=0.025). Higher serum cholesterol (441.62±61.46 mg/dL vs 389.12±72.18 mg/dL; <0.001) and lower serum albumin (15.74±2.20 gm/L vs 17.30±2.99 gm/L; p=0.004) were seen in cases than control. Conclusion: Lower age of onset, history of atopy, infection, higher serum cholesterol and lower serum albumin level during initial attack were associated .......

Optimal Trough Concentration of Tacrolimus in Pediatric Patients With Primary Nephrotic Syndrome.

The trough concentration (C0) of tacrolimus in children with nephrotic syndrome (NS) has rarely been explored, so its target level was based on transplant research. This study aimed to determine the optimal tacrolimus C0 in NS children. Data from primary NS children treated with tacrolimus at Wuhan Children's Hospital in the last 10 years were retrospectively collected. According to the cutoff C0 analyzed by receiver-operator characteristics (ROC) analysis, patients were divided into very low- (< 4 ng/mL), low- (4-5 ng/mL), medium- (5-7 ng/mL), and high-concentration (7-10 ng/mL) groups. A total of 196 patients were enrolled for primary outcome analysis. Compared to medium-concentration group, only the very low-concentration group obtained significant inferior primary outcomes, including overall remission rate, relapse-free survival rate, and relapse rate at 6 months. For secondary outcomes, the very low-concentration group experienced more frequent treatment failure in 12 months, whereas the high-concentration group suffered a higher risk of adverse events than the medium-concentration group. For steroid-resistant NS, very low- and low-concentration groups required longer time to achieve remission compared to medium-concentration group. For steroid-sensitive NS, the very low-concentration group suffered a higher relapse frequency than medium-concentration group. Lastly, the dose of tacrolimus required for children with different CYP3A5 genotypes with or without Wuzhi capsules was analyzed. In conclusion, tacrolimus may be targeted to C0 of 4-7 ng/mL during the first 6 months in children with NS. For steroid-resistant NS, C0 of 5-7 ng/mL can achieve a rapid remission.

Evaluation of thyroid profile among children aged 1-15 years with nephrotic syndrome: An observation study.

The interaction between the kidney and the thyroid is important for normal function of both organs. In nephrotic syndrome, proteinuria leads to loss of several proteins, which in turn causes hypothyroidism. To assess the thyroid function in children with nephrotic syndrome. This cross-sectional study was conducted in a tertiary center, Bhopal, from February 2020 to January 2021. Consecutive children aged 1-15 years admitted with nephrotic syndrome (first-time diagnosed and all relapse cases) were included in the study. A thyroid profile was sent along with routine investigations, and thyroid hormone status was assessed in nephrotic syndrome children. Of the 70 patients, 39 (55.7%) showed abnormal thyroid profiles; 19 (27.1%) had overt hypothyroidism, and 20 (28.6%) had subclinical hypothyroidism. Overt hypothyroidism was seen in 16.1% of newly diagnosed cases, 40% of second relapses, and 2.7% of frequently relapsed cases (P < 0.001). The mean serum free T3 and free T4 levels in frequent relapses were 2.50 ± 0.39 ng/dL and 0.78 ± 0.12 ng/dL, respectively, which were significantly lower than in newly diagnosed cases (2.77 ± 0.37 ng/dL and 0.91 ± 0.19 ng/dL, respectively). The mean thyroid-stimulating hormone (TSH) level was significantly higher in frequent relapses 5.86 ± 1.56 µIU/mL) and second relapse (5.81 ± 1.78 µIU/mL) than in newly diagnosed cases (4.83 ± 0.76 µIU/mL) and first relapse cases (4.74 ± 1.17 µIU/mL), (P < 0.01). An abnormal thyroid profile was commonly observed in children with nephrotic syndrome, and overt hypothyroidism was more common in frequent relapse cases. Therefore, thyroid screening should be a part of the management of nephrotic syndrome so that hypothyroidism can be detected and managed at an early stage.

Prevalence and associated factors of infection in children with nephrotic syndrome aged 2-18 years in the northwest and east Amhara region, Ethiopia: a multi-center cross-sectional retrospective study

BackgroundInfection is the most common complication of pediatric patients with nephrotic syndrome. The factors associated with infection in nephrotic syndrome are lacking. The objective of the study was to identify the prevalence and associated factors among children with nephrotic syndrome aged 2 to 18 years.MethodsWe conducted a hospital-based retrospective cross-sectional study. The data collector installed an Epi5 collector electronic data-collecting tool from Google Play. Then, we exported the data to Stata version 15.1 for analysis. The mean, standard deviation, frequency, and percentage were used for descriptive statistics. The logistic regression model was used to identify the factors associated with infection.ResultsIn this study, the prevalence of infection among nephrotic syndrome children is 39.8% (95%CI: 30.7, 49.7). The types of infection identified were pneumonia, urinary tract infection, diarrheal disease, cutaneous fungal infection, intestinal parasitic infection, and sepsis. The presence of hematuria increased the odds of infection by 5-times. On the other hand, low level of serum albumin increased the odds of infection by 7%. Being a rural resident increased the odds of infection by 3.3-times as compared to urban.ConclusionsSerum albumin level, presence of hematuria, and rural residence were significantly associated with infection. We recommended a longitudinal incidence study on large sample size at multicenter to strengthen this finding.

#1093 Remission rates and long-term outcomes of relapsed idiopathic nephrotic syndrome children treated with cyclophosphamide vs. cyclosporin A

Abstract Background and Aims Approximately seventy percent of nephrotic syndrome (NS) children experience relapse episodes which are classified as frequently-relapsing nephrotic syndrome (FRNS), steroid-dependent nephrotic syndrome (SDNS), or steroid-resistant nephrotic syndrome (SRNS). In such cases, immunosuppressive drugs are combined to reduce the steroid side effects and prolong the remission period. However, the benefit of immunosuppressants and their side effects should be balanced. Objectives This study aimed to determine the remission rates and long-term outcomes of FRNS, SDNS, and SRNS children treated with cyclophosphamide vs. cyclosporin A (Cy A). Methods A retrospective review of medical records of children (aged &amp;lt; 15 years) with relapsed idiopathic nephrotic syndrome at Prince of Songkla University Hospital, southern Thailand during 2010-2021 was conducted. Demographic data, treatment responses, and adverse events were recorded. The remission rates, incidences of infection and acute kidney injury (AKI) in FRNS/SDNS and SRNS were compared between oral cyclophosphamide and Cy A treatments. Results There were 148 relapsed NS children, 102 (68.9%) boys, with a median age of 4.6 (IQR 2.5-8.4) years. FRNS, SDNS, and SRNS accounted for 37 (25.0%), 50 (33.8%), and 61 (41.2%) children, respectively. The cyclophosphamide treatment group (N = 135) had significantly higher remission rates in FRNS/SDNS than SRNS (63/85 (74.1%) vs. 11/50 (22.0%), P &amp;lt; 0.001), while the difference in remission rates in the Cy A treatment group (N = 53) was not statistically significant between FRNS/SDNS and SRNS (14/20 (70.0%) vs. 18/33 (54.5%), P = 0.265). Patients who had the Cy A treatment had significantly higher proportions of infections and AKI than children in the cyclophosphamide treatment group (20/53 (37.7%) vs 10/95 (10.5%), P &amp;lt; 0.001 and 21/53 (39.6%) vs 9/95 (9.5%), P &amp;lt; 0.001, respectively). Of the 148 children, at a median follow-up time of 8.7 (IQR 5.2–12.2) years, 21 (14.2%) and 9 (6.1%) children had developed chronic kidney disease (CKD) stage III or end-stage kidney disease (ESKD), respectively. The mean duration from CKD stage III to ESKD was 5.0+5.5 months. Conclusions Seventy percent of FRNS/SDNS children achieved remission with either Cy A or cyclophosphamide, but the SRNS children achieved remission proportionately better with Cy A than cyclophosphamide. However, the Cy A-treated children had higher proportions of infections and AKI than the cyclophosphamide treatment group. Overall, one-fifth of the relapsed childhood NS children developed CKD.

Comparison of Serum IgE Level between Initial Attack and Relapse Cases of Idiopathic Nephrotic Syndrome in Children

Background: Nephrotic Syndrome (NS) is a common and recurrent glomerular disease in childhood. Although the exact etiology of NS is not fully known, it is believed that immune system plays a pivotal role in its pathogenesis. Studies have been reported a strong association between NS and increased level of serum immunoglobulin E (IgE). In addition, children with recurrent NS, the IgE level significantly increases, and there is a higher relapse rate.&#x0D; Objective: The aim of the study was to determine the difference of Serum IgE level between initial attack and relapse cases of idiopathic Nephrotic Syndrome in children.&#x0D; Methodology: A cross sectional analytical study has been conducted on 35 initial attack and 35 relapse cases of idiopathic Nephrotic Syndrome children admitted in the Department of paediatrics, Sir Salimullah Medical College Mitford Hospital (SSMCMH), Dhaka from May 2021 to April 2022. Study subjects were enrolled by purposive sampling after confirming the diagnosis and fulfilling the inclusion and exclusion criteria. Informed written consent was taken from each patient's legal guardian before enrollment. A detailed history and thorough physical examination was done in each patient on admission. With all aseptic precaution five ml of venous blood was collected and sent for serum albumin, serum cholesterol and serum IgE level measurement. Data were analyzed using the statistical package for social sciences (SPSS) version 23.0. Independent sample t test or Mann-whitney test was used to compare data between groups. P value of less than 0.05 was considered as significant.&#x0D; Results: The mean age of the studied samples was 3.86 (ranging from 2 to 6 years). Moreover, among the studied sample male was a little bit greater than female. A significant prevalence of relapse cases were found among the children with middle income family status (P&lt;0.05).Spot urine protein and creatinine ratio and serum cholesterol level was significantly higher in patients experience relapse attack (P&lt;0.05). However, serum albumin level was quite similar in both cases. The mean serum IgE of patients experiencing relapse attack was 985.11+433.65 which was significantly higher than patients experiencing initial attack 470.48+227.35 (P&lt;0.001). &#x0D; Conclusion: This study showed that serum IgE levels are higher in relapse cases of Nephrotic Syndrome than that of initial attack. Furthermore, serum IgE is more in frequent relapse as compared to infrequent relapse. Serum IgE levels have a positive correlation with disease activity and relapse of Nephrotic Syndrome.

Elevated Levels of Urinary Podocyte-Derived Microparticles in Nephrotic Syndrome

BACKGROUND: Nephrotic syndrome (NS) is the most common glomerular disease in childhood. The proposed hypothesis for the pathogenesis of this disease has changed over time, from immune dysregulation theory and systemic circulating factors theory, to the growing recognition of podocytopathies’ role. The existance of podocytopathies is usually examined by using podocyte-derived microparticles (MPs), such as nephrin, podocin, and podocalyxin (PCX). Therefore in this study, the difference between nephrin, podocin, and PCX expressions in NS children and healthy children was investigated.METHODS: An observational cross-sectional study was conducted, involving 33 children with NS and 22 age-matched healthy children as controls. Urine samples were collected from each subject in the early morning, before being processed and incubated with antibodies to detect nephrin, podocin, and PCX. The processed samples were then analyzed with flow cytometer methods.RESULTS: NS subjects had significantly higher expression of all three urinary podocyte-derived MPs compared to the control subjetcs. Nephrin, podocin, and PCX showed good discrimination in NS subjects with the area under curve (AUC) of 0.895, 0.849, and 0.728, respectively.CONCLUSION: This study revealed the differential expression of podocyte proteins in NS subjects compared to healthy controls. This supports the role of podocytopathies in the pathogenesis of NS. Therefore, nephrin, podocin, and PCX might have potentials to be future non-invasive diagnostic tools in glomerular disease.KEYWORDS: nephrin, nephrotic syndrome, podocalyxin, podocin, podocyte, urinary microparticle

Successful Therapy of Infarct Stroke with Nephrotic Syndrome in Children: A Rare Case Report

Introduction: Nephrotic syndrome (NS) is characterized by swelling, proteinuria, hypoalbuminemia, or hyperlipidemia. The incidence of NS depends on the country and ethnicity and is highest in Asia than in Europe. Nephrotic syndrome can cause complications such as arterial thromboembolism (ATE) due to a hypercoagulable state. Case Presentation: We encountered a 9-year-old boy with NS and infarct stroke, which was treated with corticosteroid and low molecular weight of heparin with clinical improvement. Conclusions: We recommend that all NS children with high platelet levels perform thromboelastography (TEG) examination and use prophylactic anticoagulation with monitoring of bleeding risk during therapy.

Rituximab-associated hypogammaglobulinemia in children with idiopathic nephrotic syndrome: results of an ESPN survey

BackgroundThere is paucity of information on rituximab-associated hypogammaglobulinemia (HGG) and its potential infectious consequences in children treated for idiopathic nephrotic syndrome (INS).MethodsA survey was distributed by the European Society Pediatric Nephrology to its members. It addressed the screening and management practices of pediatric nephrology units for recognizing and treating RTX-associated HGG and its morbidity and mortality. Eighty-four centers which had treated an overall 1328 INS children with RTX responded.ResultsThe majority of centers administered several courses of RTX and continued concomitant immunosuppressive therapy. Sixty-five percent of centers routinely screened children for HGG prior to RTX infusion, 59% during, and 52% following RTX treatment. Forty-seven percent had observed HGG prior to RTX administration, 61% during and 47% >9 months following treatment in 121, 210, and 128 subjects respectively. Thirty-three severe infections were reported among the cohort of 1328 RTX-treated subjects, of whom 3 children died. HGG had been recognized in 30/33 (80%) of them.ConclusionsHGG in steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) children is probably multifactorial and can be observed prior to RTX administration in children with SDNS/FRNS. Persistent HGG lasting >9 months from RTX infusion is not uncommon and may increase the risk of severe infections in this cohort. We advocate for the obligatory screening for HGG in children with SDNS/FRNS prior to, during, and following RTX treatment. Further research is necessary to identify risk factors for developing both HGG and severe infections before recommendations are made for its optimal management.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Nephrotic Syndrome: Epidemiological, Clinical, Paraclinical and Therapeutic Profile

Background: End-stage kidney disease has several causes, including nephrotic syndrome (NS). Steroid- resistant nephrotic syndrome (SRNS) children are a difficult subset of nephrotic syndrome patients who frequently respond poorly to conventional immunosuppression. Objective: The goals of our research are to analyze the different types of nephrotic syndrome, to study the epidemiological, clinical and paraclinical profile, as well as to present the difficulty in managing steroid-resistant nephrotic syndrome. Methods: Our study is a cross-sectional analysis of all patients hospitalized or followed in consultation, who were diagnosed with a nephrotic syndrome at the pediatric B department of the university hospital center Mohamed VI in Marrakech, from January 2011 to January 2022. Results: We gathered 447 instances, with an annual incidence of 41 cases. The children's ages varied from 12 days to 16 years, with an average of 5 years and 9 months. Pure nephrotic syndrome was found in 302 patients and 145 patients were carriers of impure nephrotic syndrome. In our study, 81.5% of patients had nephrosis as the cause of deseas. Secondary NS was seen in 11% of the patients, infant form was found in 6% and 1.5% of cases were congenital. The treatment was mainly based on oral corticosteroid therapy. 71.4% of the patients were corticosensitive of which 45.3% became corticodependent while 28.6% of the cases were corticoresistant. Corticosteroid boluses were used in 53% of cases. Immunosuppressants were prescribed in 31.5% of patients. Conclusion: In children, nephrotic syndrome is a common and chronic illness. It is of particular interest because of the frequency of nephroses, multiple relapses, the difficulties of management and the psychological and school impact on the child.

ASSESSMENT OF INFLUENZA VACCINATION STATUS IN CHILDREN WITH NEPHROTIC SYNDROME

Background: Nephrotic syndrome (NS) is a common kidney disease in childhood. Children with this condition are at higher risk of developing vaccine-preventable diseases. Prednisolone remains the mainstay for the treatment of NS. Giving influenza vaccination to NS children will significantly lower the risk of NS relapse during the post-vaccination period. Aims and Objectives: To assess the influenza vaccination status in children with nephrotic syndrome. Materials and Methods: Parents/guardians of 69 pediatric patients (&lt;18 years old) diagnosed with NS from February 2022 to January 2023 were surveyed to evaluate influenza immunization status and parental knowledge regarding flu vaccination recommendations. Results:Among 69 patients included in the study, 7 children (10.1%) were vaccinated with inactivated influenza vaccine. Among the 62 parents of unvaccinated children, 21 (33.9%) had concerns about the safety of influenza vaccination, 18 (29%) had concerns about the cost of such vaccine, 17 (27.4%) were not aware of the proper recommendations and 6 (9.7%) had been told by their neighbors and relatives not to vaccinate with such vaccine. Conclusions:Physicians must be aware that proper information oninfluenza vaccination recommendations must be provided to family members along with the safety and efficacy profile of the vaccine for successful influenza vaccination in childhood nephrotic syndrome.

A critical role of the podocyte cytoskeleton in the pathogenesis of glomerular proteinuria and autoimmune podocytopathies.

Selective glomerular filtration relies on the membrane separating the glomerular arterioles from the Bowman space. As a major component of the glomerular filtration barrier, podocytes form foot processes by the actin cytoskeleton, which dynamically adjusts in response to environmental changes to maintain filtration barrier integrity. The slit diaphragms bridge the filtration slits between neighboring foot processes and act as signaling hubs interacting with the actin cytoskeleton. Focal adhesions relay signals to regulate actin dynamics while allowing podocyte adherence to the basement membrane. Mutations in actin regulatory and signaling proteins may disrupt the actin cytoskeleton, resulting in foot process retraction, effacement, and proteinuria. Large-scale gene expression profiling platforms, transgenic animal models, and other in vivo gene delivery methods now enhance our understanding of the interactions among podocyte focal adhesions, slit diaphragms, and actin dynamics. In addition, our team found that at least 66% of idiopathic nephrotic syndrome (INS) children have podocyte autoantibodies, which was defined as a new disease subgroup-, autoimmune podocytopathies. This review outlines the pathophysiological mechanisms of podocyte cytoskeleton protein interactions in proteinuria and glomerular podocytopathy.

MEAN LEVEL OF PROTEIN C, PROTEIN S AND ANTITHROMBIN III IN PEDIATRIC NEPHROPATHIC SYNDROME

The triad of clinical symptoms linked with proteinuria of nephrotic range, including hypoalbuminemia and edema, is known as nephrotic syndrome. When body excrete more than40 mg/m2/hr of protein or a first morning protein: creatinine ratio of more than 2-3: 1 then we call it proteinuria of nephrotic range.(1)It is estimated that the vast majority of children with nephrotic syndrome have some form of primary or idiopathic sickness, with minimal change disease being the most prevalent.Thromboembolic consequences are more common in people who have nephrotic syndrome. (2) This study tends to shed light if there is increase or decrease in level of protein C, S or antithrombin III in nephrotic syndrome. OBJECTIVE: To determine the mean level of protein C, protein S and AT Ill in children with nephrotic syndrome. SETTING: The research was conducted at Department of Haematology at Children Hospital Lahore. STUDY DESIGN: Cross sectional study. DURATION OF STUDY: The study was completed in six months from 25-08-2017 to 29-02-2018. DATA COLLECTION PROCEDURE: Patients fulfilling the inclusion criteria were taken for Protein C, Protein S and Antithrombin III assays Collect blood 3ml (9 vol) in 0.109M (3.2%) anticoagulant (1 Vol) and Centrifuge. All centrifuge specimens were run in DIAGNOSTIC STAGO. Results: A total of 100 children with nephrotic syndrome were enrolled after fulfilling inclusion criteria. The mean age of the children was 6.26±2.72 month. 69(69%) were male children. Protein C level was 95.31±16.02, Protein S level 84.05±13.31 and antithrombin III level was 86.50±16.36. Conclusion: Protein C, S and Antithrombin III level were within normal range. Further studies are needed to delineate the exact pathogenesis behind thromboembolic phenomenon in nephrotic syndrome children.

Evaluation of Acute Kidney Injury and its Risk Factors in Children Admitted with Diagnosis of Nephrotic Syndrome

Abstract Background and Aim: Acute Kidney Injury (AKI) is an important complication of Nephrotic Syndrome (NS) associated with adverse outcome. The frequency of AKI has increased to almost double in the last decade. To determine the incidence of AKI, risk factors and its association with outcome in hospitalized children with NS. Methods – All children aged 1-18 years with diagnosis of NS from 01 November 2018 to 31 May 2020 were enrolled for the study. AKI was diagnosed using the KIDIGO 2012 guidelines and classified according to pediatric RIFLE definition. Results –The mean age of children in this cohort was 4.7± 2.8 years. Complications were observed in 67% cases only. Among all complications the most frequent complication was anemia (25%). The incidence of AKI in hospitalized children with NS was 18.6%. According to pRIFLE criteria of AKI; 11.6% of children met Stage 1 (risk) criteria, 4.6% met Stage 2 (injury) criteria and 2.3% met Stage 3 (failure) respectively. Among all NS children, 53% received nephrotoxic drugs during the hospital stay. On applying multivariate logistic regression analysis, only male gender, associated anemia and Vancomycin use in NS patients came out to be significant independent risk factor for acute kidney injury. Conclusions: AKI is more frequent in first episode of NS rather than in any type of relapses. Although, nephrotoxic drug and male gender are known independent risk factors for development of AKI, associated anemia is till yet not considered as independent risk factor for AKI in children with NS.

POS-448 CORTICOSTEROID SPARING AGENTS IN FREQUENT RELAPSING AND STEROID DEPENDENT NEPHROTIC SYNDROME IN CHILDREN: A SINGLE CENTER RETROSPECTIVE STUDY

Children with frequently relapsing nephrotic syndrome (FRNS) or Steroid-dependent nephrotic syndrome (SDNS) may be prescribed non-corticosteroid immunosuppressive agents whenever there is a failure to maintain remission with low-dose alternate-day prednisone and/or significant adverse effects of prednisone develop. A wide variety of immunosuppressive agents have been used in these patients to reduce the number of relapses and maintain remission. A retrospective study was conducted on all steroid-sensitive nephrotic syndrome (SSNS) children (1-11 years) who received any type of second line agents (e.g. CNI, MMF, cyclophosphamide, and Rituximab) over a period of 9 years from January 2010 to January 2019 in pediatric nephrology unit in Prince Sultan Military Medical City, Riyadh. The study included 24 patients. Their age at diagnosis ranged between 1 and 11 years with a mean of 3.8 years and standard deviation of (±) 2.6 years. During the first year of steroid therapy, relapse occurred among 87% of patients; of them, the number of relapses being 4 or more in 21.7%. Regarding indication for the second line of treatment, SDNS was the most frequent reported (60.9%), followed by FRNS (30.4%). Concerning agents used in the second line, MMF ranked first (58.4%), followed by Cyclophosphamide (33.3%). Number of relapses after starting steroid sparing agent was more than once among 41.7% of patients. Duration of remission after starting steroid sparing agent ranged between 2 and 72 months (14±14.1). Overall response to the second line of treatment was observed among majority of patients (91.7%). Renal biopsy was performed in 45.8% of patients. Concerning side effects of steroid sparing agents, electrolytes disturbances and hypertension were reported by two (8.3%) and one (4.2%) patients respectively. Duration of remission was significantly longer among patients treated with cyclosporine (48±33.9 months) compared to other lines of treatment, p<0.001. On the other hand, hypertension was only reported among patients treated with cyclosporine, p=0.003. The overall response of children with SDNS and FRNS to the second line agents was significant, with favorable longer remission free period with Cyclosporine use with no major side effects. Our results affected by the retrospective design of the study, as well as the small sample size. Therefore larger scale study with prospective design is highly encouraged.

Prediction of steroid resistance and steroid dependence in nephrotic syndrome children

BackgroundSteroid resistant (SR) nephrotic syndrome (NS) affects up to 30% of children and is responsible for fast progression to end stage renal disease. Currently there is no early prognostic marker of SR and studied candidate variants and parameters differ highly between distinct ethnic cohorts.MethodsHere, we analyzed 11polymorphic variants, 6 mutations, SOCS3 promoter methylation and biochemical parameters as prognostic markers in a group of 124 Polish NS children (53 steroid resistant, 71 steroid sensitive including 31 steroid dependent) and 55 controls. We used single marker and multiple logistic regression analysis, accompanied by prediction modeling using neural network approach.ResultsWe achieved 92% (AUC = 0.778) SR prediction for binomial and 63% for multinomial calculations, with the strongest predictors ABCB1 rs1922240, rs1045642 and rs2235048, CD73 rs9444348 and rs4431401, serum creatinine and unmethylated SOCS3 promoter region. Next, we achieved 80% (AUC = 0.720) in binomial and 63% in multinomial prediction of SD, with the strongest predictors ABCB1 rs1045642 and rs2235048. Haplotype analysis revealed CD73_AG to be associated with SR while ABCB1_AGT was associated with SR, SD and membranoproliferative pattern of kidney injury regardless the steroid response.ConclusionsWe achieved prediction of steroid resistance and, as a novelty, steroid dependence, based on early markers in NS children. Such predictions, prior to drug administration, could facilitate decision on a proper treatment and avoid diverse effects of high steroid doses.

Comparison the Serum Level of Paraoxonase Activity in Frequent Relapse and Infrequent Relapse Patients with Nephrotic Syndrome

Nephrotic syndrome (NS) is distinguished by heavy proteinuria (urine protein:creatinine ratio ?2000 mg/gor ?300 mg/dL, or 3+ protein on urine dipstick), hypoalbuminemia (?2.5 g/dL), and edema. Leakage ofmassive amounts of serum proteins into the urine leads to a hypercoagulable state, a higher rate of infectiousdisease, and the dysregulation of fluid balance. Idiopathic nephrotic syndrome (INS)is one of the most common renal problems in children encountered in day-to-day nephrology practices.The present study was aimed to evaluate the oxidant/ antioxidant status by measuring paraoxonase (PON)activities as well as total antioxidant capacity in steroid sensitive nephrotic syndrome (frequent and infrequentrelapse) and compares it with healthy control children . Paraoxonase activity by spectrophotometer in threegroups consisted of age and sex matched (30) patients with Frequent relapse nephrotic syndrome FRNS ,(30) patients with infrequent relapse nephrotic syndrome (IFRNS) and (30) healthy control children. Theserum level of paraoxonase activity in infrequent relapse group was 101.61±43.0 IU which far less thanfrequent relapse group (160.44±44.22 IU) or controls (228.35±32.35 IU) with highly significant differences.Of note, the difference between control group and frequent relapse group was highly significant.

Effect of Supportive Care Activities on Negative Emotional Feelings of Children with Nephrotic Syndrome

Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine,low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weightgain, feeling tired, and foamy urine. Complications may include blood clots, infections, and high bloodpressure.Aim of the study: This study was aimed to assess the effect of supportive care activities on negative feelingsof nephrotic syndrome children. Setting: The study was carried out at medicine department of children’shospital affiliated to Ain Shams University Hospitals. The subjects: The subject of this study was purposivesample composed of (50) children were attended to the previously mentioned setting and accompanyingmothers. Tools of data collection: An Interviewing Questionnaire, Children’s Assessment of Participationand Enjoyment (CAPE),multidimensional Scale of Perceived Social Support (MSPSS).Results: Less than half of the studied children having negative Emotional Feelings.Conclusion: The study concluded that the studied children with Nephrotic Syndrome have negative feelingsneed Supportive Care.Recommendations: This study recommended the importance of Encourage use of Supportive care activitiesprograms to help them to prevent the negative feelings of Nephrotic syndrome children.

Clinical Analysis of Primary Nephrotic Syndrome Complicated by Plastic Bronchitis in Children.

To summarize the clinical features of primary nephrotic syndrome (PNS) complicated by plastic bronchitis (PB) in children to provide guidance for treatment. We conducted a retrospective review of the clinical data of 25 children hospitalized with NS complicated by PB in our Hospital between 10/2016 and 03/2019, and summarized the clinical manifestations, imaging and fiberoptic bronchoscopy (FOB) examinations, treatment course and outcome of them. 1). The 25 children, with a nephrotic syndrome (NS) course of one to 36 months, were all diagnosed with PB after FOB, among which 8 cases (32%) had respiratory failure and required ventilatory support. All of them started with respiratory symptoms such as fever and cough, and then suffered from dyspnea and progressive aggravation after 1-3 day(s) of onset, with rapid occurrence of bidirectional dyspnea and even respiratory failure in severe cases. 2). Laboratory test for pathogens: influenza A virus H1N1 (11 cases), influenza B virus (9 cases), adenovirus (3 cases) and mycoplasma pneumoniae (2 cases). There was no statistically significant difference (P>0.05) between children with common NS complicated by influenza virus (IV) infection (not accompanied by dyspnea) and those with kidney disease who developed PB in the white blood cell count, lymphocyte count, the inflammatory biomarkers C-reactive protein (CRP), procalcitonin (PCT) and humoral immunity (IgG level), yet the total IgG level was found significantly higher and the blood albumin level lower in the latter (P<0.05). 3). The 25 children were all examined with the FOB and treated with lavage, 15 of which had typical bronchial tree-like casts and 10 broken and stringy casts. Based on histopathological classification, all children were of Type I. 4). Twenty children (80%) with influenza were administered the antiviral drug Oseltamivir, 20 (80%) were treated with antibiotics, oral hormones were replaced with the same dosage of intravenous Methylprednisolone for 5 cases (20%), and 20 (80%) were intravenously administered gamma globulins (400-500 mg/kg x 3 days). These children showed a remarkable improvement after treatment and there were no deaths. NS children are at high risk of influenza virus infection. Children with a severe case of NS are more susceptible to PB. If symptoms like shortness of breath, wheezing and progressive bidirectional dyspnea occur, FOB examination and lavage treatment should be performed as early as possible. Hyper-IgE-emia and hypoproteinemia may be the high risk factors for PNS complicated by PB in children. ZIEL: Ziel der Studie war es, durch Zusammenfassung der klinischen Merkmale des primären nephrotischen Syndroms (PNS) mit komplizierender plastischer Bronchitis (PB) im Kindesalter eine Orientierungshilfe für die Therapie der Erkrankung zu geben. Wir führten eine retrospektive Prüfung der klinischen Daten von 25 Kindern durch, die zwischen Oktober 2016 und März 2019 in unser Krankhaus aufgenommen wurden, und erstellten eine Zusammenfassung der klinischen Symptome, Untersuchungen mit bildgebenden Verfahren und fiberoptischer Bronchoskopie (FOB), des Therapieverlaufs und des Outcomes der Patienten. 1). Bei den 25 Kindern bestand ein nephrotisches Syndrom (NS) über einen Zeitraum von einem bis 36 Monaten. Bei allen Patienten wurde die Diagnose PB nach FOB gestellt, wobei in 8 Fällen (32%) eine beatmungspflichtige respiratorische Insuffizienz vorlag. Alle Patienten zeigten anfänglich Symptome einer Atemwegserkrankung wie Fieber und Husten, gefolgt von Atemnot und progredienter Verschlechterung 1 bis 3 Tage nach Erkrankungsbeginn. Dabei kam es rasch zum Auftreten bidirektionaler Atemnot, in schweren Fällen bis hin zur respiratorischen Insuffizienz. 2). Laboruntersuchung auf Erreger: Influenza-A-Virus H1N1 (11 Fälle), Influenza-B-Virus (9 Fälle), Adenovirus (3 Fälle) und Mycoplasma pneumoniae (2 Fälle). Es fand sich kein statistisch signifikanter Unterschied (P>0,05) zwischen Kindern, die ein "gewöhnliches" NS mit komplizierender Influenza-Virus (IV)-Infektion (ohne begleitende Atemnot) aufwiesen, und Kindern mit Nierenerkrankung, die eine PB entwickelten, hinsichtlich der Leukozyten- und Lymphozytenwerte sowie der Entzündungsmarker C-reaktives Protein (CRP), Procalcitonin (PCT) und humorale Immunität (IgG-Wert). Allerdings wurde bei der letzteren Patientengruppe ein signifikant höherer Gesamt-IgG-Wert und ein signifikant niedriger Albumin-Spiegel im Blut nachgewiesen (P<0.05). 3). Bei allen 25 Kindern erfolgte eine FOB und Therapie mit Lavage, bei 15 Kinder fanden sich typische verzweigte Ausgüsse der Bronchialäste und bei 10 Patienten desintegrierte und zähe Ausgüsse. Gemäß der histopathologischen Klassifikation waren alle Kinder vom Typ I. 4). Zwanzig Kinder (80%) mit Influenza erhielten das Virostatikum Oseltamivir, 20 Kinder (80%) eine Antibiotikatherapie, in 5 Fällen (20%) wurden oral gegebene Hormone durch intravenös in derselben Dosis verabreichtes Methylprednisolon ersetzt und 20 Kinder (80%) erhielten intravenös verabreichte Gammaglobuline (400-500 mg/kg Körpergewicht x 3 Tage). Diese Kinder zeigten eine bemerkenswerte Verbesserung nach der Therapie und es traten keine Todesfälle auf. Bei Kindern mit NS besteht ein hohes Risiko für eine Influenza-Virus-Infektion. Kinder mit schwerem NS sind anfälliger für PB. Bei Auftreten von Symptomen wie Atemnot, Giemen und Brummern sowie progredienter bidirektionaler Dyspnoe sollte baldmöglichst eine FOB-Untersuchung und eine therapeutische Lavage durchgeführt werden. Erhöhte IgE-Werte im Blut und Hypoproteinämie stellen möglicherweise Risikofaktoren für PNS mit komplizierender PB im Kindesalter dar.