Steroid-dependent Nephrotic Syndrome Research Articles

Relapse during and after regular single-dose rituximab treatment in adult patients with steroid-dependent nephrotic syndrome.

Rituximab is widely used in patients with steroid-dependent nephrotic syndrome. However, information on the effect of long-term rituximab treatment is limited. This study examined the efficacy of rituximab during and after treatment in adult patients with steroid-dependent nephrotic syndrome. This retrospective cohort study included 30 patients with steroid-dependent nephrotic syndrome. Patients received regular single-dose rituximab (500mg) intravenously every 6months. Discontinuation of rituximab was considered after four to six doses if there was no recurrence of nephrotic syndrome. Glucocorticoid discontinuation with remission, first relapse after rituximab initiation, and relapse after regular rituximab treatment discontinuation were evaluated. The median age was 38 (range 18-67) years. Of 30 patients, 13 and 17 were men and women, respectively. Prior to rituximab treatment, the median number of nephrotic syndrome relapses in the patients was 5 (range 2- > 20). The 1year discontinuation rate of glucocorticoids with remission was 83%. All patients discontinued glucocorticoid treatment at least once until 3years and 7months. The 1 and 2year relapse rates after initiation of rituximab treatment were 0% and 3%, respectively. 25 patients discontinued regular rituximab treatment after a median number of six (4-12) doses. Six patients relapsed after discontinuing rituximab, and the 1 and 2year relapse rates after the last regular rituximab treatment were 9% and 25%, respectively. All patients with steroid-dependent nephrotic syndrome who received rituximab could discontinue glucocorticoid treatment with remission, and three-fourths of the patients remained in remission for > 2years after discontinuing rituximab treatment.

Daily compared with alternate-day levamisole in pediatric nephrotic syndrome: an open-label randomized controlled study.

Levamisole is less expensive and has a better toxicity profile compared to other steroid sparing agents used in nephrotic syndrome. It has a plasma half-life of 2.0 to 5.6hours, but is conventionally administered on alternate days. We aimed to assess whether daily levamisole is safe and more effective than standard alternate-day therapy in maintaining remission in children with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). An open-label randomized controlled trial was conducted in children with FR/SDNS. Group A received daily while Group B received alternate-day levamisole (2-3mg/kg/dose) for 12months. Prednisolone was tapered off by 3months. Patients were monitored for relapses, further steroid requirement, and adverse effects. A total of 190 children with FR/SDNS (94 in Group A and 96 in Group B) were analyzed. Sustained remission for 12months was observed in 36% of Group A and 27% of Group B patients (p = 0.18). Numbers completing 12months in the study were 67% in Group A and 56% in Group B (p = 0.13). Time to first relapse, persistent FR/SDNS, and withdrawal due to poor compliance were statistically similar in both groups, while relapse rate and cumulative steroid dosage were significantly lower in Group A compared to Group B (p = 0.03 and p = 0.02, respectively). The incidence of adverse effects was comparable in both groups, with reversible leucopenia and hepatic transaminitis being the commonest. Daily levamisole therapy was not superior to alternate-day therapy in maintaining sustained remission over 12months. Nevertheless, relapse rate and cumulative steroid dosage were significantly lower without increased adverse effects.

#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.

#2623 Homeostatic Model Assessment (HOMA) in pediatric patients with nephrotic syndrome receiving tacrolimus

Abstract Background and Aims Children with nephrotic syndrome (NS) receive diabetogenic drugs like tacrolimus (TAC) and steroids. TAC is toxic to pancreatic β-cells and suppresses insulin production in a time and dose dependent manner. This is well documented in renal transplant patients who develop post-transplant diabetes mellitus (PTDM). Although overt diabetes is uncommon in children receiving TAC for NS, the subclinical effect on β cell function has not been studied. Our aim was to study pancreatic beta cell function as assessed by homeostasis model assessment (HOMA) indices in children with NS who received TAC therapy for at least 1 year duration. Method We performed a prospective descriptive study where we followed children (1-18 years) with NS who received TAC therapy for at least 1 year. We noted patient demographics, clinical and histologic pattern of NS, cumulative steroid dose (mg/kg/day) received 90 days prior and TAC C0 levels. Fasting insulin, blood sugar to calculate HOMA indices for IR (insulin resistance), HOMA % β for beta cell function, HOMA-IS (insulin sensitivity), C-peptide and HbA1C were done once at study inclusion and yearly intervals when required. Statistical analysis included Pearson's correlation, paired t test and regression analysis. Results We performed HOMA indices in 37 children (19 males, 18 females) between September 2021-February 2023. Six patients had 2 measurements during the study period. The mean age of onset of NS was 28 months (95% CI [20; 36]) and mean age at HOMA indices measurement was 69 months (95% CI [59; 79]). Of the 37 patients, 54% (20/37) had late steroid resistance, 32% (12/37) had early steroid resistance, 8% (3/37) had steroid dependent NS, 6% (2/37) had frequently relapsing NS. Kidney biopsy performed in 36 children showed minimal change disease in 55.5% (20/36) and focal segmental glomerulosclerosis in 44.5% (16/36). The mean TAC duration, TAC Co level and mean cumulative steroid dose received in last 90 days were 27 months (95% CI [22;32]), 4.54 ng/ml (95% CI [4.12;4.97]) and 0.36 mg/kg/d (95% CI [0.28;0.44]) respectively. Eleven (30%) patients had cutaneous signs of insulin resistance like acanthosis nigricans and 9 (24%) patients had fasting blood sugar of >100 mg/dl. In Pearson's correlation analysis we found positive correlation between TAC Co level, HOMA IR (r = 0.4, P = 0.008) and TAC Co, HOMA %β (r = 0.44, P = 0.003) and cumulative steroid dose, fasting blood glucose (r = 0.3, P = 0.46). There was negative correlation between TAC Co level, HOMA IS (r = −0.4, P = 0.007). In regression analysis, only TAC Co level significantly influenced all HOMA indices including insulin resistance, insulin sensitivity and beta cell function. A HbA1C of > 5.7 (pre-diabetes range) was found in 32.4% (12/37) patients which warrants further monitoring. C-peptide levels were significantly higher after 12 months of TAC therapy in 6 patients who had two measurements (p = 0.032). Conclusion Tacrolimus therapy for nephrotic syndrome in children can affect pancreatic beta cell function as assessed by HOMA indices. Long term monitoring of pancreatic beta cell function in children with NS on TAC is needed to assess the full extent of these subclinical alterations.

#1927 Efficacy and safety of ripertamab in paediatic glomerular disease

Abstract Background and Aims Anti-B-cell treatment has been shown to be an efficient tactic for glomerular disease. Ripertamab as a novel anti-CD20 monoclonal antibody developed by China, has been structurally optimized to specifically bind to the transmembrane antigen CD20, with an amino acid difference in the constant region sequence compared to rituximab. This study reports the efficacy and safety of ripertamab in children with different glomerular diseases. Method We retrospectively report the data of 140 children with a diagnosis of glomerular disease and a treatment with ripertamab in a single center Results A total of 140 children (age, 11.2 ± 3.7 years; 58.6% boys) were included, 69/140 (49.3%) steroid-dependent nephrotic syndrome (SDNS), 38/140 (27.1%) steroid-resistant but CNIs-dependent nephrotic syndrome, 18/140 (12.9%) Lupus nephritis, 5/140 (3.6%) atypical hemolytic uremic syndrome, 4/140 (2.9%) ANCA associated vasculitis, 3/140 (2.1%) membranous nephropathy and 3/140 (2.1%) IgA vasculitis nephritis. The Median (IQR) duration of disease before the application of ripertamab was 4.4 (2.3, 7.4) years. They totally received 200 courses of ripertamab. A total of 83, 55, 1, and 1 patient received one, two, three, and four courses, respectively. Ripertamab 375 mg/m2 (maximum 500 mg) were injected per course. B cell depletion could be observed in 129/140 (92.1%) children one month after ripertamab. An additional course was administered due to recovery of B-cells or relapse. Median (IQR) follow-up was 0.8 (0.5, 1.1) years. The median relapse-free period after the first course was 4.7 months (IQR, 3.8, 5.6 months). Most of the relapses developed simultaneously with recovery of B-cells. About 36.7% of these children stopped steroid during the follow-up. One or more immunosuppressant (IS) drugs needed before ripertamab infusion could be withdrawn or reduced in 109/140 patients (77.9%). None of the patients developed life-threatening adverse events. Conclusion This study suggests that ripertamab could be an effective and safe treatment for various pediatric glomerular diseases.

Rituximab Induced Rare Cystic Lesion in Lungs in a Nephrotic Child: A Case Report

Rituximab has been extensively used for managing B-cell lymphomas due to its anti-CD20 monoclonal antibody activity. Over the last decade, its application has been extended to manage frequent relapsing or steroid-dependent nephrotic syndrome. Its use has been comparatively safe, but few cases of adverse effects on the lung have been reported in the adult population. These lung injury presentations are rarely reported in a pediatric group with only four cases in the literature. Below is a rare case of rituximab-induced lung injury in a 9-year-old boy with frequent relapse of nephrotic syndrome, which developed after four days of rituximab infusion. Suspecting infection and sepsis, several antibiotics were started, but with no improvement in respiratory complaints, even antifungal and antituberculosis treatments were initiated. Finally, setting up a casual relation with the time of infusion to the development of complaints, association with rituximab was suspected. The patient responded to steroid therapy with complete resolution of respiratory complaints. To our knowledge, this is the first reported case of rituximab-induced cystic lesion in lungs from India.

A Case of Dasatinib Induced Nephrotic Syndrome in a Chronic Myeloid Leukemia Patient with Steroid Dependent Nephrotic Syndrome

A Case of Dasatinib Induced Nephrotic Syndrome in a Chronic Myeloid Leukemia Patient with Steroid Dependent Nephrotic Syndrome

Rituximab versus tacrolimus as corticosteroid-sparing therapy for children with steroid-dependent nephrotic syndrome: A systematic review and meta-analysis of randomized and nonrandomized controlled trials

ABSTRACT Objectives: Prolonged use of corticosteroids induced complicated course in children with steroid-dependent nephrotic syndrome (SDNS), and the use of tacrolimus, a first-line alternative calcineurin inhibitor (CNI) agent was related to some unwanted adverse effects. Rituximab, a second alternative treatment has been proven to reliably reduce the number of relapses within 12 months with minimal adverse effects. Materials and Methods: Our review follows Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. All the databases were derived from MEDLINE, Proquest, EBSCOhost, Wiley, and Google Scholar within the past 11 years. The risk of bias was evaluated using the Revised Cochrane Risk of Bias Tool for Randomized Trials (RoB 2) and Risk of Bias in Non-Randomized Studies of Interventions. Meta-analysis used Review Manager (version 5.4) with a random effect model to obtain a pooled mean difference (MD) and odds ratio with 95% confidence intervals (CIs). Results: Four studies were included based on our eligibility criteria, and only three were included in the quantitative analysis. Three studies had low and one study had a moderate risk of bias. Pooled data results indicated that Rituximab was superior to tacrolimus in reducing the number of patients with 1–2 relapses (MD = 0.44, [95% CI: 0.21–0.91]) and had higher eGFR values (MD = 6.67; [CI − 2.92–10.61]). However, Rituximab showed insignificant superiority compared to tacrolimus in reducing the number of patients with 3 relapses, sustained remission, cumulative steroid use, serum cholesterol, and serum albumin concentrations. Conclusion: Rituximab exhibits more advantages in treating SDNS compared to tacrolimus, although the treatment options are highly individualized. Both regimens must also be weighed against their potential side effects to achieve a better overall health status.

Impact of childhood nephrotic syndrome on obesity and growth: a prospective cohort study.

Children with nephrotic syndrome are at risk of obesity and growth impairment from repeated steroid treatment. However, incidence and risk factors for obesity and short stature remain uncertain, which is a barrier to preventative care. Our aim was to determine risk, timing, and predictors of obesity and short stature among children with nephrotic syndrome. We evaluated obesity and longitudinal growth among children (1-18years) enrolled in Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics. We included children with nephrotic syndrome diagnosed between 1996-2019 from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Primary outcomes were obesity (body mass index Z-score ≥ + 2) and short stature (height Z-score ≤ -2). We evaluated prevalence of obesity and short stature at enrolment (< 1-year from diagnosis) and incidence during follow-up. Cox proportional hazards models determined the association between nephrotic syndrome classification and new-onset obesity and short stature. We included 531 children with nephrotic syndrome (30% frequently relapsing by 1-year). At enrolment, obesity prevalence was 23.5%, 51.8% were overweight, and 4.9% had short stature. Cumulative incidence of new-onset obesity and short stature over median 4.1-year follow-up was 17.7% and 3.3% respectively. Children with frequently relapsing or steroid dependent nephrotic syndrome within 1-year of diagnosis were at increased risk of new-onset short stature (unadjusted hazard ratio 3.99, 95%CI 1.26-12.62) but not obesity (adjusted hazard ratio 1.56, 95%CI 0.95-2.56). Children with ≥ 7 and ≥ 15 total relapses were more likely to develop obesity and short stature, respectively. Obesity is common among children with nephrotic syndrome early after diagnosis. Although short stature was uncommon overall, children with frequently relapsing or steroid dependent disease are at increased risk of developing short stature. Effective relapse prevention may reduce steroid toxicity and the risk of developing obesity or short stature.

Levamisole in childhood idiopathic nephrotic syndrome: new promises, and advocacy for global access

In the current issue of Kidney International, Sinha etal. present data from an open-label, noninferior, randomized controlled trial comparing 12-months of alternate-day prednisolone, given daily during infection, versus levamisole, in children with frequently relapsing or steroid-dependent nephrotic syndrome. This study suggests that both of these strategies are efficacious and safe. Results of this study should redefine the role of levamisole in future guidelines, and a call for global availability of levamisole should be advocated.

A Rare Pediatric Case of Allopurinol-Induced Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Successfully Treated With Intravenous Immunoglobulins

Allopurinol-induced drug reaction syndrome with eosinophilia and systemic symptoms (A-DRESS) is a well-described condition in adults, whereas it is uncommon among children. We describe a case of A-DRESS in a 16-year-old male with steroid-dependent nephrotic syndrome. He presented a life-threatening clinical course with persisting fever, skin rash, eosinophilia, lymphadenopathy, distributive shock, and herpesvirus 6 detection. The withdrawal of allopurinol and a combination of intravenous immunoglobulins (IVIGs) and systemic corticosteroids led to the patient’s recovery without sequelae. Drug reaction with eosinophilia and systemic symptoms (DRESS) in pediatrics is rare and can present in a severe form. Early diagnosis and timely treatment are critical for prognostic purposes. This report suggests the potentially crucial role of IVIG in the treatment of patients with A-DRESS.

WCN24-1037 Minimal change glomerulonephritis steroid-dependent nephrotic syndrome treated with Rituximab

WCN24-1037 Minimal change glomerulonephritis steroid-dependent nephrotic syndrome treated with Rituximab

Immunosuppressive agents for frequently relapsing/steroid-dependent nephrotic syndrome in children: a systematic review and network meta-analysis.

This study aimed to systematically compare the efficacy of various immunosuppressive agents in treating pediatric frequently relapsing or steroid-dependent nephrotic syndrome (FRSDNS). We conducted systematic searches of PubMed, Embase, the Cochrane Library, and the Web of Science up to May 23, 2023. Outcome measures included relapses within 1 year, mean cumulative exposure to corticosteroids, patients with treatment failure at 1 year, relapse-free survival during 1 year, and adverse events. The quality of the included studies was evaluated using the modified Jadad scale, the Methodological Index for Non-Randomized Studies (MINORS), and the modified Newcastle-Ottawa Scale (NOS). Rituximab was found to be the most likely (92.44%) to be associated with the fewest relapses within 1 year and was also most likely (99.99%) to result in the lowest mean cumulative exposure to corticosteroids. Rituximab had the highest likelihood (45.98%) of being associated with the smallest number of patients experiencing treatment failure at 1 year. CsA was most likely (57.93%) to achieve the highest relapse-free survival during 1 year, followed by tacrolimus (26.47%) and rituximab (30.48%). Rituximab showed no association with serious side effects and had comparable adverse effects to ofatumumab and tacrolimus. Rituximab may be the most favorable immunosuppressive agent for treating pediatric FRSDNS. Nephrologists should consider this drug, along with their clinical experience, patient characteristics, and cost considerations, when choosing a treatment approach.

Septic arthritis following mumps in a case of steroid dependent nephrotic syndrome: a case report

Nephrotic syndrome is a common renal disorder with an incidence of 20 to 40 per million population in developed countries. Children with nephrotic syndrome are especially susceptible to infections such as cellulitis, spontaneous bacterial peritonitis, and bacteremia. However, septic arthritis is an extremely rare complication in nephrotic syndrome. A 6-year-old girl with steroid dependent nephrotic syndrome relapsed following mumps parotitis and developed swelling of the right knee with restricted movements. Ultrasonography (USG) and magnetic resonance imaging (MRI) were suggestive of septic arthritis. The child responded to intravenous Vancomycin and Ceftazidime. We present a rare complication of nephrotic syndrome as septic arthritis, previously reported only once.

Early Rituximab as an Add-On Therapy in Children With the Initial Episode of Nephrotic Syndrome

The approximately 70% 12-month relapse in children experiencing the initial episode of steroid-sensitive nephrotic syndrome (SSNS) is a significant concern, with over 50% developing frequent relapses or steroid-dependent nephrotic syndrome (FRNS/SDNS). There is a lack of strategies to reduce relapse after the onset. Whether early administration of rituximab, which effectively reduces relapses in FRNS/SDNS, may be a solution has not been evaluated. A prospective, multicenter, open-label, single-arm trial was conducted in China, with a 12-month follow-up. Children aged 1 to 18 years with the first episode of nephrotic syndrome (NS) were screened for eligibility. Proteinuria was evaluated daily using dipsticks. A dose of 375 mg/m2 of rituximab was intravenously infused within 1 week after achieving corticosteroid-induced remission. The main outcome was 12-month relapse-free survival. Out of the initially 66 children screened, 44 were enrolled and received rituximab, with all but 1 participant completing the 12-month follow-up. The median age at diagnosis was 4.3 years (interquartile range [IQR]: 3.4-5.9), and 33 (77%) of the participants were male. In the rituximab group, the 12-month relapse-free survival was significantly higher compared to historical controls (32 of 43 [74.4%] vs. 10 of 33 [30.3%]; P< 0.001; hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.80-7.81). The post hoc analysis revealed a higher 24-month relapse-free survival and a lower incidence of FRNS/SDNS at the 12-month follow-up. Treatment with rituximab was well-tolerated. Our findings support that early administration of rituximab may be associated with a higher 12-month relapse-free survival and a reduced incidence of FRNS/SDNS in children experiencing the initial episode of SSNS.

Using real-world data to inform dosing strategies of rituximab for pediatric patients with frequent-relapsing or steroid-dependent nephrotic syndrome: a prospective pharmacokinetic-pharmacodynamic study.

Objectives: Rituximab is frequently used off-label for the treatment of frequent-relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). However, the optimal dosing schedules remain undetermined. The objective of this study was to establish a population pharmacokinetic-pharmacodynamic (PK-PD) model in pediatric patients with FRNS/SDNS, and to investigate dosing regimens that provide adequate suppression of B lymphocytes. Methods: A prospective, open-label, single-center study was conducted in Nephrology Department at Children's Hospital of Fudan University, and a two-compartment PK model of rituximab in pediatric FRNS/SDNS has been developed previously by our group. CD19+ lymphocyte count profiles were obtained from these patients. The presence of anti-rituximab antibodies was assessed prior to medication in children who had previously received rituximab or during follow-up at the last sampling point for PK analysis. PK-PD analyses were performed to describe the changes of CD19+ lymphocytes, with rituximab assumed to increase their death rate. Monte Carlo simulation was conducted to evaluate different dosing regimens. Results: In total, 102 measurements of CD19+ lymphocyte counts were available for PK-PD analysis. No detectable levels of anti-rituximab antibodies were observed during the PK follow-up period. A turnover model with saturable stimulatory action of rituximab on the removal of lymphocytes best characterized the relationship between rituximab concentration and CD19+ lymphocyte counts, where the Emax and EC50 were estimated to be 99.6*106/L and 5.87μg/mL, respectively. Simulations indicated that a single infusion of 750mg/m2 and 2 infusions of 375mg/m2 both yielded a 10-week suppression of CD19+ lymphocytes. Conclusion: This study represents a first attempt to quantitatively describe the PK-PD relationship of rituximab in pediatric patients with FRNS/SDNS, and provide a potential pathway for future precision dosing strategy for rituximab therapy. Further clinical studies are warranted to evaluate the efficacy and safety of different dosing schemes.

Retrospective Cross-Sectional Study Reviewing the Effectiveness of Mycophenolate Mofetil on Saudi Children With Nephrotic Syndrome.

Background Idiopathic nephrotic syndrome (INS) is the most common form of nephrotic syndrome (NS) in children. It is often associated with minimal change disease (MCD). Corticosteroid therapy is the initial treatment, but many patients experience relapses, leading to steroid-dependent nephrotic syndrome (SDNS) or frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). To avoid prolonged steroid use, mycophenolate mofetil (MMF) is used as an immunosuppressive alternative. MMF is safe and effective for treating SDNS and FR-SSNS in children, with studies showing reduced relapse rates. The current study aims to evaluate MMF's effectiveness and safety in Saudi children with NS and identify factors that affect its efficacy. Methods A retrospective cross-sectional study was conducted at King Abdullah Specialized Children's Hospital (KASCH) in Riyadh, Saudi Arabia. The study included children aged one to 14 years diagnosed with NS who received MMF therapy. Data were collected from medical records from 2000 to 2020. Ethical considerations were followed, and statistical analysis was performed using IBM SPSS Statistics for Windows, version 25 (released 2017; IBM Corp., Armonk, New York, United States). Baseline characteristics and responsiveness to MMF were examined. Results In our study, 45 participants (25 males, 20 females) with NS were treated with MMF. Most participants were steroid-dependent (84.44%) and had frequent relapses. MMF was effective in 84.4% of cases, with a significant reduction in relapse; the mean number of relapses decreased from 3.5 before MMF to 1.6 after MMF (p-value = 0.00002). Moreover, 40% of the participants were completely free of relapse after the introduction of MMF. The average duration of the MMF therapy was 45 months. Post-MMF side effects were rare but documented. Gastrointestinal symptoms were extremely rare. Elevated liver enzyme levels were reported in 8.88% (four cases) of the participants. Leukopenia, a more common adverse effect, was reported in 26.66% of cases during the MMF therapy. The average daily dose of steroid was reduced from 12.5 mg/day pre MMF to 2 mg/day post MMF with a p-value of 0.00229. Conclusion Our study evaluated the use of MMF in 45 participants with NS. We found that MMF was effective in 84.4% of cases, leading to a significant reduction in the number of relapses. Post-MMF side effects were relatively rare, except for leukopenia that was reported in 26.66%. In addition, the average rate of reduction of steroid exposure before and after MMF was significant. These findings suggest that MMF is a promising treatment option for children with NS and an alternative therapy to long-term steroid use, due to its safety and effectiveness, although close monitoring for potential side effects is essential.

Efficacy of Rituximab for Minimal Change Disease and Focal Segmental Glomerulosclerosis with Frequently Relapsing or Steroid-Dependent Nephrotic Syndrome in Adults: A Chinese Multicenter Retrospective Study

Introduction: Rituximab has been proven effective and safe in pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). We aimed to analyze the efficacy and safety of rituximab in adult FR/SDNS patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Methods: A retrospective cohort study at three nephrology centers in China included adult FR/SDNS patients with biopsy-proven MCD or FSGS. Primary outcomes were relapse frequency and first relapse-free survival time. Adverse events were well recorded, and logistic regression analyses were used to investigate the risk factors of relapse. Results: Eighty-one patients (age, 25.0 years; interquartile range, 20.0–40.5; 67% males; 82.7% MCD) received an average rituximab dose of 1,393.8 ± 618.7 mg/2 years during the 2-year follow-up period. The relapse frequency, calculated as the ratio of relapse times to follow-up years, significantly decreased after rituximab treatment (0.04 [0.00, 0.08] vs. 1.71 [1.00, 2.45], p < 0.001). The first relapse-free survival time was 16.7 ± 8.0 months. Fifty-seven patients (70.4%) achieved cessation of corticosteroids and immunosuppressants within 3 months after the first rituximab infusion. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. Low serum albumin level before rituximab and high CD56⁺CD16⁺ natural killer cell count after rituximab were independent risk factors of relapse within 2 years after rituximab treatment. Conclusion: Rituximab was proven an effective and safe treatment option for adult FR/SDNS patients with MCD or FSGS in maintaining disease remission and minimizing corticosteroid exposure.

Patients with primary focal segmental glomerulosclerosis with detectable urinary CD80 are more similar to patients with minimal change disease in clinicopathological features

Background Focal segmental glomerulosclerosis (FSGS) is an important cause of refractory nephrotic syndrome (NS) in children and adults. Urinary CD80 is elevated in some patients with primary FSGS, however, its clinical value is not fully clarified. This study aims to evaluate the clinical and pathological significance of urinary CD80 in patients with primary FSGS. Methods Sixty-one adult patients with biopsy-proven primary FSGS, with standard treatment and long-term follow up, were enrolled retrospectively. Urinary CD80, on the day of kidney biopsy, was measured using commercial ELISA kits and adjusted by urinary creatinine excretion. Their associations with clinical and pathological parameters were investigated. Results Urinary CD80 was detectable in 30/61 (49.2%) patients, who presented with a higher level of proteinuria (10.7 vs. 5.8 g/24h; p = 0.01), a lower level of serum albumin (19.3 ± 3.9 vs. 24.2 ± 8.2 g/L; p = 0.005), a higher prevalence of hematuria (70.0 vs. 38.7%; p = 0.01), and showed a lower percentage of segmental glomerulosclerosis lesion [4.8 (3.7–14.0) vs. 9.1 (5.6–21.1) %; p = 0.06]. The cumulative relapse rate was remarkably high in these patients (log-rank, p = 0.001). Multivariate analysis identified that the elevated urinary CD80 was an independent risk factor for steroid-dependent NS (OR 8.81, 95% CI 1.41–54.89; p = 0.02) and relapse (HR, 2.87; 95% CI 1.29–6.38; p = 0.01). Conclusions The elevated urinary CD80 is associated with mild pathological change and steroid-dependent cases of primary FSGS adults, which indicates these patients are more similar to minimal change disease (MCD) in clinicopathological features.

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.