Frequently Relapsing Nephrotic Syndrome Research Articles

Comparison of Efficacy of Cyclophosphamide Versus Tacrolimus in Children With Steroid Dependent and Frequent Relapsing Nephrotic Syndrome

Objectives: To compare the efficacy of Cyclophosphamide and Tacrolimus in the management of steroid dependent and frequent relapsing nephrotic syndrome in children. Study Design: Quasi Experimental Study. Place and Duration of Study: Department of Pediatric Nephrology, The Children's Hospital & The Institute of Child Health, Multan, from July 2020 to Dec 2020. Methodology: A total of 120 patients presenting with steroid dependent and frequent relapsing nephrotic syndrome that need 2nd line drug were divided in two groups. Group A included patients using Cyclophosphamide in a dose of 2.5mg/kg and group B used Tacrolimus in a dose of 0.1mg/kg. All patients were monitored and compliance of drugs were noted.Efficacy was calculated as proportions of patients achieving maintained remission of disease for six months duration. Results: Our study included n=80(66.7%) boys versus n = 40(33.3%) were girls having mean age 5.93±2.10 years (range 1 – 12 years). Mean weight was noted to be 17.1±3.84 kilograms. Majority 46cases (76.6%) in Tacrolimus–group achieved complete remission compared to 22cases (36.6%) in Cyclophosphamide-group, that results in usually exceedingly noteworthy p<0.005. Partial remission and drug resistance were 12cases (20%) and 2cases (3.33%) of Tacrolimus–group compared to 20cases (33.3%) and 18cases (30%) in Cyclophosphamide-group respectively. Sustained remission at 6months follow-up was 40cases (66.7%) in Tacrolimus–group compared to 16cases (26.6%) in Cyclophosphamide-group. Conclusion: Tacrolimus was more effective in inducing remission (76.6%) as compared to cyclophosphamide (36.6%) in steroid dependent and frequent relapsing Nephrotic syndrome.

Clinical analysis of sirolimus therapy in children with refractory nephrotic syndrome

To investigate the clinical efficacy of sirolimus in treating children with refractory nephrotic syndrome, the clinical data for 22 children from the Children's Hospital of Hebei Province were analyzed retrospectively. There were 16 boys and six girls, and the treatment period was from September 2015 to April 2021. There were two patients with steroid-dependent nephrotic syndrome (SDNS), six patients with frequently relapsing nephrotic syndrome (FRNS), and 14 patients with steroid-resistant nephrotic syndrome (SRNS). All patients were defined as having refractory nephrotic syndrome. There were 12 patients (including nine SRNS patients and three FRNS patients) with minimal change disease (MCD), three patients (three SRNS patients) with focal segmental glomerular sclerosis (FSGS), one FRNS patient with mesangial proliferative glomerulonephritis (MsPGN), and six patients without a kidney biopsy. Compared with levels before sirolimus treatment, 24-hour urine protein (24-h UP), low-density lipoprotein cholesterol (LDL-C), urea (Ur) and serum creatinine (SCr) levels were significantly lower (all p < 0.05). Moreover, albumin (Alb) was significantly increased (p < 0.05), and there were no significant differences in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), immunoglobulin A (IgA), immunoglobulin G (IgG) or immunoglobulin M (IgM) (all p > 0.05) at the first follow-up. Sirolimus is effective as the first treatment of some children with refractory nephrotic syndrome, but its long-term efficacy and adverse reactions still require follow-up.

#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.

THE PREVALENCE AND RISK FACTORS FOR ARTERIAL HYPERTENSION IN CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME

Objective: Arterial hypertension (AH) is claimed to be an uncommon finding in children with idiopathic nephrotic syndrome (INS). The study aimed to analyze blood pressure, prevalence, and risk factors of AH in children with INS. Design and method: In 153 children with INS (9.32±3.84 years, 100 boys), we evaluated systolic and diastolic blood pressure (mm Hg, Z-scores), age at onset of the disease, anthropometric data, response to steroids, results of kidney biopsy, number of INS relapses, and medications. Results: The mean age at disease onset was 4.39±2.38 years; 67 patients had steroid-sensitive nephrotic syndrome (SSNS), 12 frequently relapsing nephrotic syndrome (FRNS), 58 steroid-dependent nephrotic syndrome (SDNS), and 16 steroid-resistant nephrotic syndrome (SRNS). Kidney biopsy was performed in 26: 5 – minimal change disease, 11 – mesangial proliferation, 10 – focal and segmental glomerulosclerosis. AH at disease onset was found in 10 (6.5%) patients in the following 11 (7.2%) after corticosteroid initiation. The observation period was 4.93±3.80 years, and AH was found in 31 (20.3%) – in 3 (4.5%) patients with SSNS, 2 (16.7%) with FRNS, 20 (34.5%) with SDNS, and 6 (37.5%) with SRNS. Patients with AH had lower height Z-score (-0.46±1.20 vs. 0.18±1.15, p=0.006), higher BMI Z-score (1.15±1.10 vs. 0.41±1.09, p&lt;0.001), number of INS relapses (8.32±6.78 vs. 4.41±3.82, p&lt;0.001), and current prednisone dose (0.49±0.67 vs. 0.18±0.29 [mg/kg/24h], p&lt;0.001). Systolic blood pressure Z-score at the end of observation correlated with age (r=-0.192, p=0.017), BMI Z-score (r=0.368, p&lt;0.001), and present prednisone dose [mg/kg/24h] (r=0.186, p=0.021), diastolic blood pressure Z-score with BMI Z-score (r=0.231, p=0.004), and number of INS relapses (r=0.163, p=0.044). In Cox Proportional Hazard presence of SDNS and SRNS were the only predictors of AH (SDNS: HR=4.80, 95CI(1.30-17.75), SRNS: HR=4.77, 95CI(1.06-21.53)). Conclusions: 1. Approximately one-third of patients with SDNS and SRNS develop arterial hypertension in the course of the disease. 2. Steroid dependence and steroid resistance are the strongest predictors of AH in children with INS. Other determinants of blood pressure elevation in this group of patients are high BMI and a high number of relapses.

Pediatric frequent relapsing nephrotic syndrome with multiple cerebral infarctions accompanied by patent foramen ovale and cerebral venous sinus thrombosis: a case report

BackgroundIdiopathic nephrotic syndrome (NS) presents as a hypercoagulable state, of which thromboembolism (TE) is a well-known life-threatening complication. Although TE is more likely to occur in venous vessels than arterial vessels, arterial TE is important because it may cause after-effects, including tissue necrosis and cerebral infarction (CI); therefore, prompt diagnosis and appropriate treatment are required. We report a pediatric NS case with multiple CIs.Case presentationA 14-year-7-month-old Japanese girl was diagnosed with frequent relapsing NS, accompanied by headache and disturbance of consciousness during the second relapse. Brain magnetic resonance imaging (MRI) and four-dimensional computed tomography revealed multiple CIs, vasogenic edema, and cerebral venous sinus thrombosis (CVST). The patient had no underlying thrombophilia other than hypercoagulability due to NS and prednisolone (PSL), and no cardiac arrhythmia; however, a right-to-left shunt through the patent foramen ovale (PFO) was observed with the Valsalva maneuver by echocardiography. Therefore, we assumed that a potential cause of multiple CIs might be an embolic stroke, caused by thrombosis formed from a hypercoagulable state due to NS and PSL treatment and reached through PFO. Antiplatelet and anticoagulant therapies were administered for TE. She was treated with PSL and mycophenolate mofetil (MMF) for NS. Rituximab (RTX) was administered to prevent NS relapse after complete remission (CR). She underwent transcatheter PFO closure at age 14 years and 9 months because we considered that the right-to-left shunt through the PFO would be one of the risks for recurrent cerebral embolism when NS relapses. One year after the onset of CIs, an MRI indicated that the CVST had resolved, leaving no neurological sequelae due to CI; therefore, anticoagulant therapy was discontinued. And then she has been in CR for NS with only MMF therapy.ConclusionsCI is a serious complication in patients with NS. The pathogenesis of multiple CIs is various, including right-to-left shunt through PFO, in addition to the hypercoagulability due to NS. It is important to investigate and manage underlying risks such as PFO, besides preventing the relapses of NS by aggressive treatments using MMF and RTX, in patients with NS.

Serum lipid profile among pediatric folk with idiopathic nephrotic syndrome: An Observational Study

Introduction: The most familiar kidney disease in children is nephrotic syndrome (NS), associated with dyslipidemia and causes various cardiovascular complications. Persistent hyperlipidemia can further raise difficulties of NS and relapse cases. Earlier diagnosis and appropriate intervention increase the possibility of saving other vital organs.&#x0D; Methods: An observational study was conducted with 85 children aged 2-15 years with a history of NS. The study group was divided into first NS and second-episode relapse cases. They were further subgrouped into Frequent Relapse NS (FRNS) and Infrequent Relapse NS (IFRNS). Fasting lipid profiles were performed among active sufferers with a follow-up after 4 weeks.&#x0D; Results: The male-to-female ratio was 1.93:1. In the first episode of NS, all lipid parameters were high in the acute phase and returned to normal during remission. In relapse cases, lipid parameters were significantly higher even in remission. Serum triglyceride and very low-density lipoprotein were significantly more elevated in the FRNS group than in the IFRNS. Low-density lipoprotein was increased considerably in FRNS. Mean high-density lipoprotein was also significantly lower in the FRNS group than in the IFRNS.&#x0D; Conclusion: Persistent hyperlipidemia is most typical among FRNS. Hyperlipidemia management is urgent to prevent among pediatric NS.&#x0D; Bangladesh Journal of Medical Science Vol. 23 No. 01 January’24 Page : 39-46

Frequency of posterior cataract in steroid-dependent or frequent relapse nephrotic syndrome in children.

Objective: To determine the frequency of posterior cataract in steroid-dependent or frequent relapse nephrotic syndrome (NS) in children presenting to National Institute of Child Health (NICH), Karachi. Study Design: Cross Sectional study. Setting: Department of Pediatrics, NICH, Karachi. Period: September 2022 to February 2023. Material &amp; Methods: We enrolled children of both genders aged between 2 to 15 years with NS (frequent relapsing or steroid dependent) who were taking steroid for at least 6 months. Baseline demographic information of patients including age and gender along with duration of NS, duration of steroid treatment, present doses of steroid, and total cumulative dose of steroid were noted. Ophthalmological examination was carried out from ophthalmology department by slit lamp examination and the frequency of posterior cataract was noted. Results: In a total of 154 children, 84 (54.5%) were girls. The mean age was 3.41±1.33 years. The most common presenting features/complaints were periorbital edema, fever and pedal edema reported in 112 (72.7%), 56 (36.4%) and 36 (23.4%) children respectively. The posterior cataract was found to be present among 23 (14.9%) children. Age (p&lt;0.001), frequent relapse (p=0.001), increased duration of NS (p&lt;0.001), duration of steroid treatment (p&lt;0.001), number of relapses (p&lt;0.001) and total cumulative dose of steroids (p&lt;0.001) were significantly associated with posterior cataract. Conclusion: The frequency of posterior cataract among children having frequent relapse or steroid dependent nephrotic syndrome was 14.9%. Duration of nephrotic syndrome, duration of steroid treatment, number of relapses and cumulative steroid treatment dose were significantly linked with posterior cataract.

Effect of a Herbal Formulation on Infection Prevention and Immune Regulation in Children with Frequent Relapse Nephrotic Syndrome

Effect of a Herbal Formulation on Infection Prevention and Immune Regulation in Children with Frequent Relapse Nephrotic Syndrome

The association between dental caries and steroid-sensitive nephrotic syndrome in children.

Pathogenesis and relapse of steroid-sensitive nephrotic syndrome (SSNS) are primarily associated with infection. Dental caries is the most common chronic progressive oral infection in children. However, clinical studies of SSNS combined with dental caries in children are rare. In our retrospective cohort study from January 2021 to June 2022, 145 children with SSNS were included in the baseline analysis and 105 in the follow-up analysis. The follow-up period was 1year. The primary study endpoints were the relapse-free period and frequently relapsing nephrotic syndrome (FRNS). Secondary endpoints included the number and triggers of relapses and concomitant medications. The median age was 5.5years, with a caries rate of 60.7%, themean DMFT/dmft was 3.86, and the caries filling rate was 1.6%. Except for the lower proportion of high household income and high parental education observed in the caries group, no statistical differences were found when comparing the other baseline data with the non-caries group. The caries group had a shorter relapse-free period and a lower 1-year cumulative relapse-free survival rate (HR = 1.90, 95% CI 1.17-3.09, P = 0.009). Univariate regression analysis showed caries associated with FRNS (OR = 2.714, 95% CI 1.021-7.219, P = 0.045), but the correlation no longer remained in the multivariate analysis. Additionally, seven cases of caries-derived pulpal periapical inflammation triggered SSNSrelapses. The caries group had more infection triggers and concomitant medication use. Dental caries and relapse of SSNS are potentially associated, but careful evaluation is needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

CCL22 and Leptin associated with steroid resistance in childhood idiopathic nephrotic syndrome.

Previous studies have indicated a decrease in T regulatory cells (Tregs) among patients with steroid-resistant nephrotic syndrome. CCL22 and Leptin influenced the immune function of Tregs through their respective pathways. This study aimed to compare patients with steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) in terms of CCL22 and Leptin levels. This prospective study included 117 children diagnosed with idiopathic nephrotic syndrome (INS). Peripheral blood samples were collected before initiating steroid therapy, and serum levels of CCL22 and Leptin were measured. Patients were categorized into three groups based on their response to steroid treatment. Renal biopsies were recommended for all children diagnosed with INS, with higher acceptance rates in glucocorticoid resistance patients. Based on the response to steroid treatment, 117 children were divided as groups of SSNS (82 cases), frequent relapse nephrotic syndrome (FRNS) (10 cases), and SRNS (25 cases). A total of 41 patients underwent kidney biopsy, 11 cases (13.4%) in SSNS, 7 cases (70.0%) in FRNS and 24 cases (96.0%) in SRNS. 30 cases were minimal change disease (MCD), 9 cases were mesangial proliferative glomerulonephritis (MsPGN) and 3 cases were focal segmental glomerulosclerosis (FSGS). The levels of Leptin were significantly higher in SR patients (1208.1 ± 1044.1 pg/ml) compared to SS patients (515.4 ± 676.9 pg/ml) and controls (507.9 ± 479.8 pg/ml), regardless of the pathological type. CCL22 levels were significantly elevated in SRNS (92.2 ± 157.0 pg/ml), but the difference seemed to be attributed to the specific type of pathology, such as Minimal change disease (MCD) (127.4 ± 206.7 pg/ml) and focal segmental glomerulosclerosis (FSGS) (114.8 ± 22.0 pg/ml). For SRNS prediction, the AUC of Leptin, CCL22, and the joint prediction index were 0.764, 0.640, and 0.806, respectively. Serum levels of CCL22 and Leptin, detected prior to steroid therapy, were associated with steroid resistance in childhood INS.

Clinical presentation and prognosis in children over 10-year-old with primary nephrotic syndrome

Objective: To summary the clinical presentation and prognosis of primary nephrotic syndrome (PNS) in teenagers. Methods: The clinical data, renal pathological types and prognosis of 118 children over 10-year-old with PNS treated in the Department of Nephrology of the Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2010 to December 2020 were retrospectively analyzed, with 408 children ≤10-year-old as control group synchronously. Chi-square test was used to compare the difference of clinical types, pathologic types, response to steroids and tubulointerstitial changes between the groups. The teenagers with steroid resistant nephrotic syndrome (SRNS) were divided into initial non-responder group and late non-responder group. Kaplan-Meier method was used to compare the difference of persistent proteinuria, and Fisher's exact test for the histological types. Results: There were 118 children >10-year-old, including 74 males and 44 females, with the onset age of 12.1 (10.8, 13.4) years; and 408 children ≤10-year-old with the onset age of 4.5 (3.2, 6.8) years. The proportion of SRNS was significantly higher in patients >10-year-old than those ≤10-year-old (24.6% (29/118) vs. 15.9% (65/408), χ2=4.66, P=0.031). There was no statistical difference in the pathological types between >10-year-old and ≤10-year-old (P>0.05), with minimal change disease the most common type (56.0% (14/25) vs. 60.5% (26/43)). The percentage of cases with renal tubulointerstitial lesions was significantly higher in children >10-year-old compared to those ≤10-year-old (60.0% (15/25) vs. 23.3% (10/43), χ2=9.18, P=0.002). There were 29 cases presented with SRNS in PNS over 10-year-old, including 19 initial non-responders and 10 late non-responders. Analyzed by Kaplan-Meier curve, it was shown that the percentage of persistent proteinuria after 6 months of immunosuppressive treatments was significantly higher in initial non-responders than those of the late non-responders ((22±10)% vs. 0, χ2=14.68, P<0.001); the percentage of minimal change disease was significantly higher in patients of late non-responders than those of the initial non-responders (5/6 vs. 3/13, P=0.041). Of the 63 >10-year-old with steroid-sensitive nephrotic syndrome followed up more than one year, 38 cases (60.3%) had relapse, and 14 cases (22.2%) were frequent relapse nephrotic syndrome and steroid dependent nephrotic syndrome. Among the 45 patients followed up over 18-year-old, 22 cases (48.9%) had recurrent proteinuria continued to adulthood, 3 cases of SRNS progressed to kidney insufficiency, and one of them developed into end stage kidney disease and was administrated with hemodialysis. Conclusions: Cases over 10-year-old with PNS tend to present with SRNS and renal tubulointerstitial lesions. They have a favorable prognosis, but are liable to relapse in adulthood.

Intrapleural Streptokinase in Management of Multiloculated Pleural Effusion as a Complication of Frequent Relapse Nephrotic Syndrome - A Case Report

Treatment of pleural effusion with intrapleural administration of fibrinolytic drugs has proven to be efficient and secure. Patients with pleural effusion who receive streptokinase instillations in conjunction with chest tube draining avoid surgery and have better outcomes. Its application in multiloculated pleural effusion, which develops as a nephrotic syndrome consequence, has only occasionally been documented. We describe a case of multiloculated pleural effusion that did not react to conventional chest tube drainage but resolved completely and dramatically in response to intrapleural streptokinase.

Real-word adrenocorticotropic hormone treatment for childhood-onset nephrotic syndrome.

Current first-line anti-proteinuric treatments do not produce a satisfactory therapeutic effect in a considerable number of patients with nephrotic syndrome (NS). Interest in adrenocorticotropic hormone (ACTH) for the treatment of NS has recently been revived. The present study investigated the efficacy and safety of ACTH treatment in children with frequent relapsing NS (FRNS), steroid-dependent NS (SDNS), and steroid-resistant NS (SRNS). The ACTH treatment group was comprised of NS patients receiving ACTH treatment. Patients with serum cortisol concentrations <85.3 nmol/L and who had not received ACTH treatment previously were enrolled in the control group from January 2018 to January 2021. The maintenance dose of prednisone, the number of disease recurrences, the time of first disease relapse, immunosuppressant use, serum cortisol levels, and adverse events were recorded in both groups. Fifty-one patients were included in the ACTH group, and twenty-one patients were enrolled in the control group. Concurrent treatment with one or more immunosuppressive and/or cytotoxic treatments occurred in 92.2% and 85.7% of patients in the ACTH and control groups, respectively, throughout the study period. A greater reduction in the prednisone maintenance dose was observed in the ACTH group compared with the control group after 1 year of follow up (0.603 ± 0.445 mg/kg vs. 0.267 ± 0.500 mg/kg, p = 0.006). During the one-year study period, fewer participants experienced one or more disease relapses in the ACTH group (45.1%) compared to the control group (76.2%, odds ratio = 3.896, p = 0.016). The number of disease recurrences per patient in the ACTH group was less than that in the control group (median difference = -1, p = 0.006). The mean length of remission was 8.902 m and 7.905 m in the ACTH group and control group, respectively. A log-rank test showed a longer relapse free survival for patients in the ACTH group (p = 0.046), but the Breslow test showed no significant difference between groups (p = 0.104). Ten patients in the ACTH group successfully discontinued all drug therapies. No patients in the control group were able to discontinue drug therapy as of February 2022. ACTH, combined with multiple drugs, is effective at reducing the prednisone maintenance dose and may effectively prevent disease relapses in childhood NS.

Forecast and verification of the active compounds and latent targets of Guyuan decoction in treating frequently relapsing nephrotic syndrome based on network pharmacology

Background Our study majorly utilizes network pharmacology combined with molecular docking to explore the latent active components and associated pivotal targets of Guyuan Decoction (GYD) in the treatment of frequently relapsing nephrotic syndrome (FRNS). Methods All active components and latent targets of GYD were retrieved from TCMSP database. The target genes for FRNS in our research were obtained from the GeneCards database. The drug-compounds-disease-targets (D-C-D-T) network was established using Cytoscape 3.7.1. STRING database was applied to observe the protein interaction. Pathway enrichment analyses (GO and KEGG) were conducted in R software. Moreover, molecular docking was employed to further validate the binding activity. MPC-5 cells were treated with adriamycin to mimic FRNS in vitro and to determine the effects of luteolin on modeled cells. Results A total of 181 active components and 186 target genes of GYD were identified. Meanwhile, 518 targets related to FRNS were also revealed. Based on the intersection using a Venn diagram, 51 common latent targets were recognized to be associated with active ingredients and FRNS. Additionally, we identified the biological processes and signaling pathways involved in the action of these targets. Molecular docking analyses illustrated that AKT1 and CASP3 interacted with luteolin, wogonin, and kaempferol, respectively. Moreover, luteolin treatment enhanced the viability but inhibited the apoptosis of adriamycin-treated MPC-5 cells via regulating AKT1 and CASP3. Conclusion Our study forecasts the active compounds, latent targets, and molecular mechanisms of GYD in FRNS, which helps us to understand the action mechanism of GYD in FRNS comprehensive treatment.

The Efficacy and Safety of Rituximab in Children with Steroid-Dependent or Frequently Relapsing Nephrotic Syndrome: A Meta-Analysis of Randomized Controlled Trials

IntroductionTo explore the efficacy and safety of Rituximab (RTX) in children with steroid-dependent nephrotic syndrome (SDNS) or frequently relapsing nephrotic syndrome (FRNS) through meta-analysis.Material and methodsMeta-analysis searches were performed before November 30th, 2021, using the PubMed, Embase, Web of Science, and Cochrane Library databases to collect randomised controlled trials (RCTs). FRNS or SDNS children younger than 18 years of age were included. The RTX group was treated with RTX combined with conventional therapy, whereas the control group was given conventional therapy. Review Manager 5.3 and STATA 15.0 were used to perform the statistical analyses.ResultsOf 1450 screened articles, a total of eight studies eligible for inclusion involving 476 patients were included. As compared to the control group, the RTX group had a significantly higher rate of long-term complete remission [RR (95% CI), 1.91 (1.16, 3.14), p&lt;0.05]. RTX did not show significant improvement in the short term [RR (95% CI), 2.48 (0.85, 7.25), p=0.10]. However, the RTX group achieved a higher short-term complete remission rate when two studies with heterogeneity were excluded [RR (95% CI), 2.17 (1.65, 2.84), p&lt;0.001]. Proteinuria levels were reduced more effectively in the RTX group [MD (95% CI), −1.84 (−2.42, −1.26), p &lt;0.001)]. The RTX group and the control group had no significant differences in adverse events.ConclusionsRTX can be considered as an effective and safe treatment option for children with SDNS or FRNS. However, it is necessary to conduct further studies via RCTs to evaluate the persistent long-term effects.

Distribution of memory B cell subsets in peripheral blood of children with frequently relapsing nephrotic syndrome

To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease. A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed. Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05). Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.

Comparison of Lipid Profile in Different Types of Steroid Sensitive Idiopathic Relapsing Nephrotic Syndrome in Children during Active Disease and Remission

Introduction: Nephrotic syndrome is a disease of relapse and remission. Relapse rate is more than 80%. Hyperlipidemia and hypoalbuminemia are important characteristic of nephrotic syndrome. Hyperlipidemia persist even after remission of disease in frequent relapse nephrotic syndrome possibly due to frequent attack of disease and frequent use of steroid. Hyperlipidemia causes premature atherosclerosis, progressive renal injury leading to chronic renal failure, cardiac complications (myocardial infarction, hypertension), cerebrovascular disease and frequent relapse of nephrotic syndrome. Objectives: The aim of study was to see the lipid profile and comparison of lipid profile among different types of steroid sensitive idiopathic relapsing nephrotic syndrome during active disease and in remission. Materials and Methods: A cross sectional study included 120 ( 40 in each group) children aged 2-16 years with steroid sensitive idiopathic relapsing nephrotic syndrome patients who were admitted or attended in out patients department (OPD) in paediatric nephrology department Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, during December 2014 to December 2015. They were clinically examined and fasting lipid profile was done in each case during active disease and after one month of urinary remission. The study population were divided into three groups- Infrequent relapse nephrotic syndrome (IFRNS), frequent relapse nephrotic syndrome ( FRNS ) and steroid dependent nephrotic syndrome (SDNS) based on clinical response. Results: Total patients were 120 (40 in each group). The study showed a male predominance with a male to female ratio 2.24:1, male patients were 69%, female 31%. In all cases, there were increased mean total cholesterol, low density lipoprotein ( LDL ) , triglyceride (TG) and high density lipoprotein (HDL) was normal during active disease, more raised in FRNS and SDNS.There was significant decrease in the mean level of total cholesterol, LDL and triglyceride during remission ( p &lt;0.001). Cholesterol became normal but triglyceride and LDL remained elevated even after one month of urinary remission in FRNS and SDNS. Conclusion: Hyperlipidemia persist during remission of steroid sensitive relapsing nephrotic syndrome. Children with FRNS and SDNS should be addressed with lipid lowering medication, healthy foods and healthy life style. Multicenter prospective studies with larger sample are needed for validating the findings of the present study. Medicine Today 2022 Vol.34(2): 111-116

Çocukluk Çağı Fokal Segmental Glomerülosklerozis: Tek Merkez Deneyimi

Aim: Focal segmental glomerulosclerosis (FSGS) is one of the common causes of nephrotic syndrome (NS) in children. This study aims to determine the demographical data, clinical course, treatment and renal outcome of children with primary FSGS and report the experience of a single center. Material and Methods: A retrospective study of the long-term outcome of 38 patients with diagnosis of primary FSGS at a tertiary pediatric care hospital from the period July 2005 to July 2019 was conducted. Results: The study included 38 patients (23 female and 15 male) with FSGS, and the mean age at diagnosis was 8.5 ± 4.2 years. The mean follow-up duration was 4.8± 4.1 (1-14.6) years. Seventeen (44.7%) patients were steroid-resistant NS (SRNS) and 21 (55.3%) patients were steroid-sensitive NS (SSNS) [12 (31.6%) steroid-dependent NS (SDNS) and 9 (23.7%) frequently relapsing NS (FRNS)]. There was no significant difference between these groups in age, gender, hematuria, serum albumin and urine protein level at presentation (p &amp;gt; 0.05). Long-term follow-up showed that 47% of SRNS patients achieved complete remission, 23.5% partial remission and 29.4% resistant to all therapies. ESRD was developed 15.8% of the FSGS patients. Risk factors for poor prognosis were the presence of hypertension (HT) at admission, female gender, and unresponsiveness to initial treatment. Conclusion: Focal segmental glomerulosclerosis in childhood, shows changes in response to treatment and prognosis. In this study, we presented our data on risk factors affecting prognosis.

Levamisole in steroid-dependent nephrotic syndrome in children: A case series

Nephrotic syndrome (NS) is a common clinical entity encountered in children and adults. Steriod Dependent Nephrotic Syndrome(SDNS) is one of the most common pediatric glomerular diseases. However, a significant chunk of cases follows a relapsing and remitting course. Various modalities such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil (MMF), levamisole, and rituximab have been tried in patients with steroid-dependent or frequently relapsing NS (FRNS). We describe our experience of using levamisole in nine patients with steroid-dependent NS. We used the regimen of levamisole dosing at 2.5 mg/kg on alternate days, along with alternate dosing of steroids at the lowest possible doses to achieve remission. During follow-up, two of the patients were switched over to a calcineurin inhibitor (tacrolimus). All the remaining seven patients responded to levamisole and attained remission. At 18 months follow-up, four patients were on a minimal dose of steroids (prednisolone 0.25 mg/kg alternate day) with levamisole 2.5 mg/kg, whereas three patients were on prednisolone 0.5 mg/kg/alternate day with levamisole 2.5 mg/kg alternate day. Among the patients with steroid-sensitive NS, 30%–60% are frequently relapsing or steroid-dependent forms of NS. Corticosteroids have well recognized and potentially serious adverse effects. A lot of steroid-sparing agents such as MMF, rituximab, alkylating agents like cyclophosphamide, and calcineurin inhibitors have been used in clinical medicine, to mitigate the above mentioned adverse effects of prolonged use of corticosteroids, with varying success. But these medications have significant side effects and toxicity profiles of their own. Our case series reiterates the role of levamisole in FRNS and SDNS patients without much risk of adverse events in patients and hence being a relatively less expensive treatment option.

Response to Chemical Pleurodesis in Children with Frequent Relapsing Nephrotic Syndrome Having Refractory Unilateral Pleural Effusion.

Idiopathic nephrotic syndrome is one of the most common chronic renal disorders in children. Associated bilateral pleural effusion is common due to the transudative process as a result of hypoalbuminemia. However, unilateral pleural effusion is a rare phenomenon and at times, unresponsive even when the patients are in remission. Here, we report two cases of frequent relapse nephrotic syndrome presented as persistent unilateral pleural effusion responsive to chemical pleurodesis, which was done with bleomycin along with normal saline.