Steroid-resistant Nephrotic Syndrome In Children Research Articles

#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 < 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 < 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 < 0.001 and 21/53 (39.6%) vs 9/95 (9.5%), P < 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.

WCN24-1789 The use of rituximab in childhood steroid-resistant nephrotic syndrome: an international, multi-centre study

WCN24-1789 The use of rituximab in childhood steroid-resistant nephrotic syndrome: an international, multi-centre study

Monogenic Causes Identified in 23.68% of Children with Steroid-Resistant Nephrotic Syndrome: A Single-Centre Study

Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of end-stage kidney disease in children, mostly associated with focal segmental glomerulosclerosis (FSGS). Advances in genomic science have enabled the identification of causative variants in 20–30% of SRNS patients. Methods: We used whole exome sequencing to explore the genetic causes of SRNS in children. Totally, 101 patients with SRNS and 13 patients with nephrotic proteinuria and FSGS were retrospectively enrolled in our hospital between 2018 and 2022. For the known monogenic causes analysis, we generated a known SRNS gene list of 71 genes through reviewing the OMIM database and literature. Results: Causative variants were identified in 23.68% of our cohort, and the most frequently mutated genes in our cohort were WT1 (7/27), NPHS1 (3/27), ADCK4 (3/27), and ANLN (2/27). Five patients carried variants in phenocopy genes, including MYH9, MAFB, TTC21B, AGRN, and FAT4. The variant detection rate was the highest in the two subtype groups with congenital nephrotic syndrome and syndromic SRNS. In total, 68.75% of variants we identified were novel and have not been previously reported in the literature. Conclusion: Comprehensive genetic analysis is key to realizing the clinical benefits of a genetic diagnosis. We suggest that all children with SRNS undergo genetic testing, especially those with early-onset and extrarenal phenotypes.

The hereditary nephrotic syndrome in children: features of clinical phenotype and genotype, pathogenesis, renal prognosis of isolated and syndromic forms

The review of the literature presents the clinical phenotype and genotype pathogenesis, renal prognosis of isolated and extra-renal manifestation form of hereditary nephrotic syndrome in children. The clinical and genetic features of hereditary steroid-sensitive and steroid-resistant nephrotic syndrome in children caused by mutations of genes encoding the main components of the slit diaphragm, glomerular basement membrane, structural and functional proteins of the podocyte are highlighted. Literature data demonstrate an unfavorable renal prognosis in children with hereditary steroid-resistant nephrotic syndrome with focal segmental glomerulosclerosis and diffuse mesangial sclerosis with clinical manifestation at the age of 0–17 years with progression to terminal renal failure at the age of 0.4–18 years. Renal replacement therapy with dialysis and kidney transplantation improves the prognosis, survival, and quality of life of children with hereditary nephrotic syndrome.

Establishment and validation of clinical prediction model for steroid-resistant nephrotic syndrome in children

Objective: To identify the clinically relevant factors of steroid-resistant nephrotic syndrome (SSNS) in children and establish a predictive model followed by verifying its feasibility. Methods: A retrospective analysis was performed in a total of 111 children with nephrotic syndrome admitted to Children's Hospital of ShanXi from January 2016 to December 2021. The clinical data of general conditions, manifestations, laboratory tests, treatment, and prognosis were collected. According to the steroid response, patients were divided into SSNS and steroid resistant nephrotic syndrome (SRNS) group. Single factor Logistic regression analysis was used for comparison between the 2 groups, and variables with statistically significant differences were included in multivariate Logistic regression analysis. The multivariate Logistic regression analysis was used to identify the related variables of children with SRNS. The area under the receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve were used to evaluate its effectiveness of the variables. Results: Totally 111 children with nephrotic syndrome was composed of 66 boys and 45 girls, aged 3.2 (2.0, 6.6) years. There were 65 patients in the SSNS group and 46 in the SRNS group.Univariate Logistic regression analysis showed that the 6 variables, including erythrocyte sedimentation rate, 25-hydroxyvitamin D, suppressor T cells, D-dimer, fibrin degradation products, β2-microglobulin, had statistically significant differences between SSNS and SRNS groups (85 (52, 104) vs. 105 (85, 120) mm/1 h, 18 (12, 39) vs. 16 (12, 25) nmol/L, 0.23 (0.19, 0.27) vs. 0.25 (0.20, 0.31), 0.7 (0.6, 1.1) vs. 1.1 (0.9, 1.7) g/L, 3.1 (2.3, 4.1) vs. 3.3 (2.7, 5.8) g/L, 2.3 (1.9,2.8) vs. 3.0 (2.5, 3.7) g/L, χ2=3.73, -2.42, 2.24, 3.38, 2.24,3.93,all P<0.05), were included in the multivariate Logistic regression analysis. Finally, we found that 4 variables including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin (OR=1.02, 1.12, 25.61, 3.38, 95%CI 1.00-1.04, 1.03-1.22, 1.92-341.04, 1.65-6.94, all P<0.05) had significant correlation with SRNS. The optimal prediction model was selected. The ROC curve cut-off=0.38, with the sensitivity of 0.83, the specificity of 0.77 and area under curve of 0.87. The calibration curve showed that the predicted probability of SRNS group occurrence was in good agreement with the actual occurrence probability, χ2=9.12, P=0.426. The clinical decision curve showed good clinical applicability. The net benefit is up to 0.2. Make the nomogram. Conclusions: The prediction model based on the 4 identified risk factors including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin was suitable for the early diagnosis and prediction of SRNS in children. The prediction effect was promising in clinical application.

Steroid-resistant nephrotic syndrome in children: Clinicohistology and pattern of response to immunosuppressive

Steroid-resistant nephrotic syndrome in children: Clinicohistology and pattern of response to immunosuppressive

Research progress of biomarkers in steroid-resistant nephrotic syndrome in children

儿童激素耐药型肾病综合征（SRNS）是临床难题，预后较差，易进展为终末期肾病。判断SRNS病理类型及进展主要靠肾活检，然而其创伤性大、不易动态监测。寻找理想的、无创的、易获得的SRNS生物标志物，对早期发现、精准诊断、有效干预、改善预后至关重要。本文回顾儿童SRNS经典生物标志物，从SRNS发病机制着手，探索和识别免疫学、遗传学、转录组学及影像学潜在生物标志物，并对其未来走向进行展望。.

Hiding in plain sight: genetics of childhood steroid-resistant nephrotic syndrome in Sub-Saharan Africa.

Steroid-resistant nephrotic syndrome (SRNS) is the most severe form of childhood nephrotic syndrome with an increased risk of progression to chronic kidney disease stage 5. Research endeavors to date have identified more than 80 genes that are associated with SRNS. Most of these genes regulate the structure and function of the podocyte, the visceral epithelial cells of the glomerulus. Although individuals of African ancestry have the highest prevalence of SRNS, especially those from Sub-Saharan Africa (SSA), with rates as high as 30-40% of all cases of nephrotic syndrome, studies focusing on the characterization and understanding of the genetic basis of SRNS in the region are negligible compared with Europe and North America. Therefore, it remains unclear if some of the variants in SRNS genes that are deemed pathogenic for SRNS are truly disease causing, and if the leading causes of monogenic nephrotic syndrome in other populations are the same for children in SSA with SRNS. Other implications of this lack of genetic data for SRNS in the region include the exclusion of children from the region from clinical trials aimed at identifying potential novel therapeutic agents for this severe form of nephrotic syndrome. This review underlines a need for concerted efforts to advance the genetic basis of SRNS in children in SSA. Such endeavors will complement global efforts at understanding the genetic basis of nephrotic syndrome.

Outcomes of steroid-resistant nephrotic syndrome in children not treated with intensified immunosuppression

BackgroundThe aim of the current PodoNet registry analysis was to evaluate the outcome of steroid-resistant nephrotic syndrome (SRNS) in children who were not treated with intensified immunosuppression (IIS), focusing on the potential for spontaneous remission and the role of angiotensin blockade on proteinuria reduction.MethodsNinety-five pediatric patients who did not receive any IIS were identified in the PodoNet Registry. Competing risk analyses were performed on 67 patients with nephrotic-range proteinuria at disease onset to explore the cumulative rates of complete or partial remission or progression to kidney failure, stratified by underlying etiology (genetic vs. non-genetic SRNS). In addition, Cox proportional hazard analysis was performed to identify factors predicting proteinuria remission.ResultsEighteen of 31 (58.1%) patients with non-genetic SRNS achieved complete remission without IIS, with a cumulative likelihood of 46.2% at 1 year and 57.7% at 2 years. Remission was sustained in 11 children, and only two progressed to kidney failure. In the genetic subgroup (n = 27), complete resolution of proteinuria occurred very rarely and was never sustained; 6 (21.7%) children progressed to kidney failure at 3 years. Almost all children (96.8%) received proteinuria-lowering renin–angiotensin–aldosterone system (RAAS) antagonist treatment. On antiproteinuric treatment, partial remission was achieved in 7 of 31 (22.6%) children with non-genetic SRNS and 9 of 27 children (33.3%) with genetic SRNS.ConclusionOur results demonstrate that spontaneous complete remission can occur in a substantial fraction of children with non-genetic SRNS and milder clinical phenotype. RAAS blockade increases the likelihood of partial remission of proteinuria in all forms of SRNS.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Kidney Organoids Generated Using an Allelic Series of NPHS2 Point Variants Reveal Distinct Intracellular Podocin Mistrafficking.

NPHS2 variants are the most common cause of steroid-resistant nephrotic syndrome in children >1 month old. Missense NPHS2 variants were reported to cause mistrafficking of the encoded protein, PODOCIN, but this conclusion was on the basis of overexpression in some nonpodocyte cell lines. We generated a series of human induced pluripotent stem cell (iPSC) lines bearing pathogenic missense variants of NPHS2 , encoding the protein changes p.G92C, p.P118L, p.R138Q, p.R168H, and p.R291W, and control lines. iPSC lines were also generated from a patient with steroid-resistant nephrotic syndrome (p.R168H homozygote) and a healthy heterozygous parent. All lines were differentiated into kidney organoids. Immunofluorescence assessed PODOCIN expression and subcellular localization. Podocytes were transcriptionally profiled and PODOCIN-NEPHRIN interaction interrogated. All variant lines revealed reduced levels of PODOCIN protein in the absence of reduced transcription. Although wild-type PODOCIN localized to the membrane, distinct variant proteins displayed unique patterns of subcellular protein trafficking, some unreported. P118L and R138Q were preferentially retained in the endoplasmic reticulum (ER); R168H and R291W accumulated in the Golgi. Podocyte profiling demonstrated minimal disease-associated transcriptional change. All variants displayed podocyte-specific apoptosis, which was not linked to ER stress. NEPHRIN-PODOCIN colocalization elucidated the variant-specific effect on NEPHRIN association and hence NEPHRIN trafficking. Specific variants of endogenous NPHS2 result in distinct subcellular PODOCIN localization within organoid podocytes. Understanding the effect of each variant on protein levels and localization and the effect on NEPHRIN provides additional insight into the pathobiology of NPHS2 variants. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_01_05_JASN2022060707.mp3.

Detection of Novel Candidate Mutations as A Cause of Steroid-resistant Nephrotic Syndrome in Children using Next-generation Sequencing Techniques

Detection of Novel Candidate Mutations as A Cause of Steroid-resistant Nephrotic Syndrome in Children using Next-generation Sequencing Techniques

Long-Term Effects of Cyclophosphamide in Sustained Remission in Childhood Steroid-resistant Nephrotic Syndrome.

Nephrotic syndrome (NS) is a chronic renal disease that can progress into end-stage renal disease within 5 years if no remission occurs. Achieving optimal remission is important to obtain better outcomes of treating childhood steroid-resistant NS (SRNS). This study aimed to determine the survival, long-term outcomes, and factors associated with the sustained remission of SRNS patients after cyclophosphamide therapy. We retrospectively studied 33 children (24 boys) with SRNS treated with cyclophosphamide therapy over 2 years. Relapse-free survival was estimated using the Kaplan-Meier method. The determinants of long-term remission were assessed by univariate and multivariate analyses using Cox's proportional hazard models. The median age at the onset of NS was 3.0 years (range: 7 months to 14.0 years). The median age at the initiation of cyclophosphamide therapy was 5.0 years (range: 1.0-15.0 years). The mean cumulative cyclophosphamide dose was 155.61 ± 16.31 mg/kg body weight. In total, 18 of 33 (54.5%) children remained in remission for 2 years after cyclophosphamide therapy, and 10 of 15 patients who relapsed (66.67%) became steroid sensitive. Relapse-free survival after cyclophosphamide therapy was 78.8%, 69.7%, and 54.5% after 6, 12, and 24 months, respectively. Cox's proportional hazard regression identified no association between remission 2 years after cyclophosphamide therapy and other factors, such as age at the onset of SRNS, type of resistance, hypertension, hematuria, administration route of cyclophosphamide, and cumulative dose (all P >0.05). Cyclophosphamide therapy appeared to be beneficial for children with SRNS for sustaining 2-year remission with a 54.5% relapse-free survival rate.

High Incidence of COL4A Genetic Variants Among a Cohort of Children With Steroid-Resistant Nephrotic Syndrome From Eastern India

High Incidence of COL4A Genetic Variants Among a Cohort of Children With Steroid-Resistant Nephrotic Syndrome From Eastern India

Rituximab Use for the Treatment of Childhood Nephrotic Syndrome by Canadian Pediatric Nephrologists: A National Survey.

Background:There is known practice variation in the treatment of frequently relapsing, steroid-dependent, and steroid-resistant nephrotic syndrome in children. Rituximab is an emerging therapy for difficult-to-treat nephrotic syndrome; however, there are no clear treatment guidelines. We therefore hypothesized that a wide variety of approaches to this therapy exist.Objective:To evaluate when and how rituximab is used for the treatment of childhood nephrotic syndrome in Canada.Design and setting:An online survey was used.Participants:Canadian pediatric nephrologists.Methods:A cross-sectional survey was distributed across Canada through the Canadian Association of Pediatric Nephrologists (CAPN) to evaluate rituximab treatment practices.Results:Of a total of 20 responses, 19 (95%) use rituximab in the treatment of nephrotic syndrome, usually as a third or fourth agent. For the number of rituximab doses, the majority (68%) uses 2 doses each time they use it. Eighteen respondents (90%) measure B cells when using this medication, mostly monthly (50%) or every 3 months (39%). Respondents were administered additional doses of rituximab prophylactically (74%) or at first relapse (47%). Long-term drug safety and drug funding were identified as the main barriers to rituximab use.Limitations:This survey represents the practice styles of physicians in a single country, and there is a nonresponse bias of 63%. Also, associations were not calculated.Conclusions:Among Canadian pediatric nephrologists, rituximab use for nephrotic syndrome appears to be increasing, but significant practice variations remain, including approaches to B-cell monitoring. It is reserved mostly for second-line and third-line use due to cost, funding issues, and residual uncertainty regarding long-term safety. Understanding these critical areas of practice uncertainty is a first step to optimize treatment of nephrotic syndrome in children.

Childhood Steroid-resistant Nephrotic Syndrome: Long-term Outcomes from a Tertiary Care Center.

Introduction:Steroid-resistant nephrotic syndrome (SRNS) is a rare condition that accounts for about 10% to 20% of all nephrotic syndromes in children. While calcineurin inhibitors induce remission in the majority, the data on long-term outcomes are limited. This retrospective study aimed to look at the clinical profile, biopsy findings, and long-term treatment outcomes in children with SRNS.Methods:The records of all children (1–18 years) with SRNS with biopsy findings of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or mesangioproliferative glomerulonephritis, who received treatment for a minimum period of 12 months and were in follow-up during the years 2007–2018 at a tertiary care teaching hospital were retrieved. The clinical, histopathological, and biochemical factors and treatment outcomes were recorded and analyzed.Results:Ninety-one (72 boys) children with a median (interquartile range [IQR]) age of onset of nephrotic syndrome as 48 (24–87) months were included. MCD and FSGS were the most common histopathological types (57.1% and 36.3%, respectively) and 62 (68.1%) patients had late steroid resistance. Calcineurin inhibitors (CNIs) were used in 86.8% of the children, and response rates with cyclosporine and tacrolimus for complete remission (CR) were 80% and 73.7%, respectively, with median (IQR) time to response being 3 (2–4) months. The presence of MCD on histology and the use of CNIs were significantly associated with CR (P < 0.01). At a median (IQR) follow-up of 5 (3–7) years, 76 (83.5%) children had either CR or partial remission, four (4.4%) developed chronic kidney disease and five (5.5%) died (three due to end-stage renal disease and two of infective complications).Conclusion:SRNS children with MCD on biopsy, late resistance, and response to CNIs have better long-term outcomes. Most patients respond to CNIs within the first 6 months of use and need therapy for at least 24 to 36 months.

Management of Steroid-Resistant Nephrotic Syndrome in Children

Nephrotic syndrome (NS) affects 115-169 children per 100,000, with rates varying by ethnicity and location. Immune dysregulation, systemic circulating substances, or hereditary structural abnormalities of the podocyte are considered to have a role in the etiology of idiopathic NS. Following daily therapy with corticosteroids, more than 85% of children and adolescents (often aged 1 to 12 years) with idiopathic nephrotic syndrome have full proteinuria remission. Patients with steroid-resistant nephrotic syndrome (SRNS) do not demonstrate remission after four weeks of daily prednisolone therapy. The incidence of steroid-resistant nephrotic syndrome in children varies between 35 and 92 percent. A third of SRNS patients have mutations in one of the important podocyte genes. An unidentified circulating factor is most likely to blame for the remaining instances of SRNS.The aim of this article is to explore and review the genetic factors and management of steroid-resistant nephrotic syndrome. An all language literature search was conducted on MEDLINE, COCHRANE, EMBASE, and Google Scholar till September 2021. The following search strings and Medical Subject Headings (MeSH) terms were used: “Steroid resistance”, “nephrotic syndrome”, “nephrosis” and “hypoalbuminemia”. We comprehensively reviewed the literature on the epidemiology, genetics, current treatment protocols, and management of steroid-resistant nephrotic syndrome.We found that for individuals with non-genetic SRNS, calcineurin inhibitors (cyclosporine and tacrolimus) constitute the current mainstay of treatment, with around 70% of patients achieving full or partial remission and an acceptable long-term prognosis. Patients with SRNS who do not react to calcineurin inhibitors or other immunosuppressive medications may have deterioration in kidney function and may develop end-stage renal failure. Nonspecific renal protective medicines, such as angiotensin-converting enzyme inhibitors, angiotensin 2 receptor blockers, and anti-lipid medications, slow the course of the illness. Recurrent focal segmental glomerulosclerosis in the allograft affects around a third of individuals who get a kidney transplant, and it frequently responds to a combination of plasma exchange, rituximab, and increased immunosuppression. Despite the fact that these results show a considerable improvement in outcome, further multicenter controlled studies are required to determine the optimum drugs and regimens to be used.

Efficacy of triple regimen of tacrolimus combined with low-dose glucocorticoid and low-dose sirolimus in treatment of steroid-resistant nephrotic syndrome in children

Efficacy of triple regimen of tacrolimus combined with low-dose glucocorticoid and low-dose sirolimus in treatment of steroid-resistant nephrotic syndrome in children

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

IntroductionSecondary 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.MethodsThis 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.ResultsThe 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.ConclusionsThe 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.

The Unique Difference Between Serum Level of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in Steroid-Resistant Nephrotic Syndrome Children Treated with an Alkylating Agent and Calcineurin Inhibitors

Background: Steroid-resistant nephrotic syndrome (SRNS) is a leading contributor to chronic kidney disease (CKD), and calcineurin inhibitors (CNIs) or monoclonal antibodies are currently the best identified therapy. Meanwhile, some developing countries still use alkylating agents (AA) such as cyclophosphamide (CPA) to treat SRNS due to economic reasons. Objectives: This study aims to determine the employability of soluble urokinase plasminogen activator receptor (suPAR) as a biomarker for monitoring therapy in SRNS children and compare the clinical improvement with those treated with an AA and CNIs. Methods: This was a retrospective cohort study conducted at Hasan Sadikin Hospital, Indonesia. The data was collected from July 2019 to July 2020 from 70 children with FSGS. Clinical signs were evaluated monthly, and serum suPAR level was measured at the third and sixth months following therapy. Two-way repeated measures ANOVA was carried out to compare the differences in suPAR level at baseline with the third and sixth months in SRNS patients who received AA and CNIs. Results: The mean age was nearly similar between the two groups based on the t-test (P = 0.140). Steroid-resistant nephrotic syndrome was more frequent in boys than in girls (P = 0.020), according to the Chi-square test. Baseline serum suPAR level was not significantly different between the two groups. In the third month, the daily urinary protein level was higher in SRNS patients that received the AA compared to the CNIs group (P &lt; 0.001). There was a significant interaction between time and treatment (F(2,138) = 7.203, P = 0.001), with higher suPAR level in SRNS patients that received the AA compared to those administered with CNIs at the 3rd and 6th months, but this difference was not statistically significant (P &gt; 0.05). Conclusions: As a noninvasive tool, suPAR is a promising modality in monitoring SRNS therapy, and CNIs have a tendency to achieve faster remission than the AA.

POS-455 RITUXIMAB IN MANAGEMENT OF PEDIATRIC NEPHROTIC SYNDROME

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1–3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Many studies in the past decade have reported the effectiveness of rituximab for complicated FRNS/SDNS and refractory SRNS. Prospective study 1) To evaluate the efficacy of rituximab in glomerular diseases. 2) To evaluate response of rituximab by complete or partial remission of nephrotic syndrome after two to four doses of rituximab 375mg/m2, during the follow up period of 12 months and the outcome had been assessed using blood and urine biochemistry values (UPCR/24hr urine protein,serum albumin) i.e., Complete remission (UPCR < 0.2), Partial remission (> 50% decrease in proteinuria from base line), CD 19 cells (< 5%) 3)To look for safety of rituximab. The patients included in the study will be given the dosage of rituximab as per body surface area (BSA) i.e., 375 mg/m2 two to four doses and followed up for a period of 12 months.REGIMEN: 375 mg/m2 Rituximab (2 doses for SDNS, 4 doses for SRNS) after premedication. Inclusion criteria: Patients of age groups <18 yrs were included in the study. Patients with nephrotic syndrome who had received a trial of steroids, alkylating agent and at least 6 months therapy of calcineurin inhibitor had received the novel drug Rituximab. Exclusion criteria: Patients with active focus of infection (Acute/Chronic). Serological evidence of current or past HIV/Hepatitis B/Hepatitis C infection. Known allergic reaction to rituximab. Patients/Parents not willing to give informed consent. Out of 33 patients who received rituximab 18 patients were in SRNS group and 11 were SDNS. The mean age of the patients who used rituximab in SDNS was 13.7+- 9.1 and in SRNS was 10.7+-2.9. In SDNS, FSGS contributed 61% (n=11); MCD33% (n=3) while in SDNS, MCD 72% (n=8); FSGS 27% (n=3). The mean duration of the CNI therapy for SRNS was 20.7=-17.1 months while for SDNS was 18.7+-10.2 months. In SRNS group; Complete remission (CR) was seen in 50.0% while in FSGS 18.1%; partial remission (PR) attained in 33.3% in MCD and in FSGS 27.2% and no remission for 16.6% in MCD and 54.4% in FSGS. In SDNS group, CR was seen in 75.0% in MCD and 33.3% in FSGS; PR obtained in 12.5% in MCD and 66.6% in FSGS; no remission in 12.5% in MCD.The CD19 counts at baseline were 12.6 ± 3.4% of the leukocyte count. After rituximab therapy, CD19 levels were 0.2 ± 0.1 and 0.3 ± 0.2% after two and four doses in patients with SDNS and SRNS, respectively. This study confirm the efficacy of rituximab in patients with difficult nephrotic syndrome; remission was achieved in 50.0% patients with SRNS and a 72.72% patients achieved remission in patients with SDNS. There was a trend toward better response rates in patients with steroid-resistant MCD (83.3%) compared with FSGS (45.45%).