Treatment Of Refractory Nephrotic Syndrome Research Articles

Rituximab treatment for refractory nephrotic syndrome in adults: a multicenter retrospective study

Background The treatment of refractory nephrotic syndrome (RNS) is full of challenges and the role of rituximab (RTX) is not well-established, thus this study aims to demonstrate the role of RTX in RNS. Methods This was a multicenter retrospective study of all adult patients receiving RTX for RNS. Patients enrolled were divided into two groups according to pathological pattern: 20 patients as a group of podocytopathy (including minimal change disease [MCD] and focal and segmental glomerulosclerosis [FSGS]), and 26 patients as membranous nephropathy (MN) group. The remission rate, relapse rate, adverse effects, and predictors of remission were analyzed. Results A total of 75 patients received RTX for RNS and 48 were available for analysis after exclusion criteria. No significant difference in the remission rate at 6 or 12 months was observed between the MCD/FSGS and MN cases (p > 0.05). The median duration of the first complete remission (CR) was 1 month in the podocytopathy group and 12.5 months in the MN group. Three relapses were associated with infection as the ultimate outcome, and 6 out of 48 remained refractory representing a response rate of 87.5% in RNS. Clinical predictors of cumulative CR were estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and mean arterial pressure (MAP) ≤103 mmHg at the beginning of therapy in patients with MN. No serious adverse effects were reported. Conclusions RTX appears to be effective in RNS across various clinical and pathological subtypes, exhibiting a low relapse rate and minimal significant side effects in the majority of patients.

Efficacy and Safety of Mizoribine in comparison with Cyclophosphamide for Treatment of Refractory Nephrotic Syndrome: Protocol for a Multi-center, Controlled, Open-label, Randomized Controlled Trial.

Nephrotic syndrome that is resistant to steroidal therapy is termed refractory nephrotic syndrome (RNS), a condition that is associated with an increased risk of end-stage renal disease (ESRD). Immunosuppressants are utilized to treat RNS, however prolonged may lead to significant adverse effects. Mizoribine (MZR) is a novel agent used in long-term immunosuppressive therapy that has few adverse effects, but data on its long-term use in patients with RNS are unavailable. We propose a trial to examine the efficacy and safety of MZR compared to cyclophosphamide (CYC) in Chinese adult patients with RNS. This is a multi-center, randomized, controlled interventional study with a screening phase (1 week) and a treatment phase (52 weeks). This study was reviewed and approved by the Medical Ethics Committees of all 34 medical centers. Patients with RNS consented to participation, and were enrolled and randomized into an MZR group or a CYC group (1:1 ratio), with each group receiving tapering doses of oral corticosteroids. Participants were assessed for adverse effects and collection of laboratory results at 8 visits during the treatment phase on week-4, week-8, week-12, week-16, week-20, week-32, week-44, and week-52 (exit visit). Participants were able to withdraw voluntarily and investigators were required to remove patients when there were safety concerns or deviations from protocol. The study started in November 2014, and was completed in March 2019. A total of 239 participants from 34 hospitals in China were enrolled. Data analysis is completed. The results are waiting to be finalized by Center for Drug Evaluation. The purpose of the current study is to evaluate the efficacy and safety of MZR in comparison with CYC for treatment of RNS in Chinese adult patients with glomerular diseases. It is the longest lasting and largest randomized controlled trial to examine MZR in Chinese patients. The results can help determine whether RNS should be considered as an additional indication for MZR treatment in China. ClinicalTrials.gov Register, NCT02257697. Registered 2014-10-01, https://clinicaltrials.gov/ct2/show/NCT02257697?term=MZR&rank=2.

Advances in the treatment of refractory nephrotic syndrome in children

Nephrotic syndrome is the most common glomerular disease in children, mostly seen in children aged 3-5 years, and is often treated clinically with hormone therapy, but some children with hormone therapy have poor results, manifesting as frequent relapses, hormone dependence or hormone-resistant refractory nephrotic syndrome, and children with long-term hormone use show adverse effects such as growth inhibition, fat metabolism disorders, and infections, which seriously affect the quality of survival. In recent years, various types of immunosuppressants have been used in children with refractory nephrotic syndrome to maintain disease remission, reduce relapses, and reduce the adverse effects of hormones, providing more therapeutic options for treatment.

Tacrolimus pharmacokinetics in pediatric nephrotic syndrome: A combination of population pharmacokinetic modelling and machine learning approaches to improve individual prediction.

Background and Aim: Tacrolimus (TAC) is a first-line immunosuppressant for the treatment of refractory nephrotic syndrome (RNS), but the pharmacokinetics of TAC varies widely among individuals, and there is still no accurate model to predict the pharmacokinetics of TAC in RNS. Therefore, this study aimed to combine population pharmacokinetic (PPK) model and machine learning algorithms to develop a simple and accurate prediction model for TAC. Methods: 139 children with RNS from August 2013 to December 2018 were included, and blood samples of TAC trough and partial peak concentrations were collected. The blood concentration of TAC was determined by enzyme immunoassay; CYP3A5 was genotyped by polymerase chain reaction-restriction fragment length polymorphism method; MYH9, LAMB2, ACTN4 and other genotypes were determined by MALDI-TOF MS method; PPK model was established by nonlinear mixed-effects method. Based on this, six machine learning algorithms, including eXtreme Gradient Boosting (XGBoost), Random Forest (RF), Extra-Trees, Gradient Boosting Decision Tree (GBDT), Adaptive boosting (AdaBoost) and Lasso, were used to establish the machine learning model of TAC clearance. Results: A one-compartment model of first-order absorption and elimination adequately described the pharmacokinetics of TAC. Age, co-administration of Wuzhi capsules, CYP3A5 *3/*3 genotype and CTLA4 rs4553808 genotype were significantly affecting the clearance of TAC. Among the six machine learning models, the Lasso algorithm model performed the best (R2 = 0.42). Conclusion: For the first time, a clearance prediction model of TAC in pediatric patients with RNS was established using PPK combined with machine learning, by which the individual clearance of TAC can be predicted more accurately, and the initial dose of administration can be optimized to achieve the goal of individualized treatment.

Study of the Therapeutic Effects of Chinese Herbal Decoction Combined with Glucocorticoid in Treating Primary Nephrotic Syndrome in Children

Background To investigate the clinical effects of Chinese medicine decoction combined with glucocorticoid in treating children with primary nephrotic syndrome. Methods A total of 70 children with pediatric nephritis nephrotic syndrome treated at Weifang People's Hospital from January 2019 to December 2019 were randomly allocated to the therapy group and the control group, each with 35 cases. The control group was treated with conventional Western medicine, and the therapy group received Western medicine and Chinese medicine. After 12 weeks of treatment, the therapeutic effect of the two groups was compared. Results After receiving the treatment, the levels of urine protein (UPro), triglyceride, and cholesterol were significantly decreased in the two groups (p < 0.05), and these levels in the therapy group were much lower than those of the control group (p < 0.05). However, the level of albumin (ALB) was predominantly increased in the two groups after treatment (p < 0.05), and this level in the therapy group was much higher than that of the control group (p < 0.05). Moreover, the immune indicators, coagulation function, and recurrence rate were noticeably improved after treatment (p < 0.05), and the therapy group was better than the control group (p < 0.05). Furthermore, the comparison of renal function indexes, liver function indexes, and blood routine between the two groups showed no statistical significance in the incidence of adverse reactions between the two groups (p > 0.05). Conclusions For the treatment of refractory nephrotic syndrome in children, based on conventional shock therapy, the addition of traditional Chinese medicine (Liuwei Dihuang pill decoction) remedy can significantly improve the disease symptoms in children and improve the efficacy, and the incidence of adverse reactions is low.

Adrenocorticotropic hormone: An expansion of our current understanding of the treatment for nephrotic syndrome

In clinical practice, we may encounter a treatment dilemma where in some patients with nephrotic syndrome are resistant to glucocorticoids or immunosuppressive agents. Thus, we currently lack viable treatment options and eagerly await the availability of new drugs. Adrenocorticotropic hormone (ACTH) had earlier been used to treat nephrotic syndrome in children, but has now become less popular owing to the advent of oral glucocorticoids. However, in recent studies, ACTH was reportedly used again for treating nephrotic syndrome, reducing proteinuria and protecting renal function, indicating a possibility for its use in the treatment of refractory nephrotic syndrome. This review analysed the validity of ACTH in these studies, focusing on the mechanism of action, application in both paediatric and adult patients with nephrotic syndrome, particularly in children, and possible side effects. We anticipate that our findings will help clinicians in treatment decision-making.

Clinical Evaluation of Tacrolimus Combined with Glucocorticoid in the Treatment of Refractory Nephrotic Syndrome

Clinical Evaluation of Tacrolimus Combined with Glucocorticoid in the Treatment of Refractory Nephrotic Syndrome

A prospective cohort study of rituximab in the treatment of refractory nephrotic syndrome

ObjectiveTo explore the efficacy and safety of rituximab (RTX) in the treatment of autoimmune nephropathy manifested as refractory nephrotic syndrome (RNS).MethodsA single-center prospective cohort study was conducted on RNS patients treated with RTX between March 2017 and December 2019. The subjects were divided into the primary nephropathy (PN) group and the secondary nephropathy (SN) group. Based on the estimated glomerular filtration rate (eGFR) before RTX treatment, the SN group was then divided into the SN-1 group (eGFR ≥ 30 ml/min) and the SN-2 group (eGFR < 30 ml/min). Biochemical parameters and clinical data were recorded during follow-up.ResultsFifty-four patients were followed up for at least 6 months. The overall remission rates were 65%, 66.7%, 27.3% in the PN, SN-1, and SN-2 groups, respectively (P = 0.022). Kaplan–Meier analysis showed a significant difference of the renal survival among the three subgroups (P < 0.001). Multivariate Cox regression analysis showed that eGFR value before treatment was an independent predictor (HR 0.919, 95%CI 0.863–0.979) for renal survival. In terms of adverse events, infection accounted for 56.6%. The incidence of severe infection was 10%, 25% and 50% in PN group, SN-1 group and SN-2 group, respectively.ConclusionsRTX may be a promising option in RNS patients with eGFR ≥ 30 ml/min/1.73m2. However, it has little effect on prognosis in patients with secondary RNS with eGFR < 30 ml/min/1.73m2, but with a high risk of severe infection.

All-case Japanese post-marketing surveillance of the real-world safety and efficacy of rituximab treatment in patients with refractory nephrotic syndrome

BackgroundRituximab is conditionally approved in Japan for use in patients with refractory nephrotic syndrome. To meet the conditions of approval, an all-case post-marketing surveillance study was conducted to confirm the real-world safety and efficacy of rituximab in patients of all ages with refractory nephrotic syndrome.MethodsAll patients scheduled to receive rituximab treatment for refractory nephrotic syndrome were eligible to register (registration: August 29, 2014 through April 15, 2016); the planned observation period was 2 years from the initiation of rituximab treatment (intravenous infusion, 375 mg/m2 once weekly for four doses). The study was conducted at 227 hospitals throughout Japan. Adverse drug reactions (ADRs) were collected for safety outcomes. The efficacy outcomes were relapse-free period and the degree of growth in pediatric (< 15 years) patients.ResultsIn total, 997 (447 pediatric) patients were registered; 981 (445) were included in the safety analysis set; 852 (402) completed the 2-year observation period; and 810 (429) were included in the efficacy analysis set. Refractory nephrotic syndrome had developed in childhood for 85.0% of patients, and 54.6% were aged ≥15 years. ADRs were observed in 527 (53.7%) patients, treatment-related infection/infestation in 235 (24.0%) patients, and infusion reactions in 313 (31.9%) patients. The relapse-free period was 580 days (95% confidence interval, 511–664). There was a significant change in height standard deviation score (pediatric patients; mean change, 0.093; standard deviation, 0.637; P = 0.009).ConclusionThe safety and efficacy of rituximab treatment in patients with refractory nephrotic syndrome were confirmed in the real-world setting.Clinical trial registrationUMIN000014997.

The combined use of Adrenocorticotropic hormone (ACTH) and Calcineurin inhibitor (CNI) in the treatment of Refractory Nephrotic Syndrome in a child

Background: Primary podocytopathies including Focal Segmental Glomerulosclerosis (FSGS) have been recognized to show variable responses to conventional treatment and overall prognosis. Persistent failure to respond to therapies remains a vexing problem for clinicians. ACTH has recently resurged as a therapy for treatment-resistant podocytopathies. We describe a case of steroid-resistant NS in a 10-year-old boy with a history of multiple failed secondary therapies, who showed partial response to biweekly ACTH therapy. Further clinical improvement was observed with the addition of the calcineurin inhibitor (CNI), tacrolimus. Case description: A 10-year-old Hispanic boy, diagnosed with frequently-relapsing steroid sensitive NS at the age of 2, and was largely relapse-free for 5 years on Cyclosporine A (CsA). Within two months after a trial off CsA, he relapsed. His course was complicated by more frequent relapses and steroid resistance. Renal biopsy performed at this time showed early focal segmental glomerulosclerosis (FSGS) and no signs of CsA-induced nephropathy. Whole exome sequencing revealed a heterozygous variant of uncertain significance in PLCE1 (Phospholipase C Epsilon 1). Trials of the steroid sparing agents tacrolimus and mycophenolate mofetil, both with and without steroids, were ineffective. He had several prolonged hospitalizations due to poorly controlled relapse. He became dependent on biweekly 25% albumin infusions. His renal function deteriorated from a baseline creatinine of 0.3 mg/dl to 0.7 mg/dl due to multiple episodes of acute kidney injury. ACTH initiated at a low dose of 40 units/1.73 m² biweekly was ineffective. Three months later, the dose was increased to 80 units/1.73 m² biweekly and he achieved partial remission and renal function returned to baseline. Tacrolimus was added at 6 months for synergy with trough levels maintained between 3-5 ng/ml. He achieved partial remission, and avoided further hospitalizations. Conclusion: ACTH alone or in combination with calcineurin inhibitor (CNI) can be a viable alternative for children who are resistant to other therapies. Variability in renal phenotype has been implicated with the PLCE1 (Phospholipase C Epsilon 1) gene. In this case, we suspect the role of his heterozygous variant PLCE1 mutation, or likely a compound heterozygous state with another unidentified mutation or modifiers or environmental factors, plays a role in the progression to a refractory NS state.

The efficacy of rituximab in the treatment of refractory nephrotic syndrome: a meta-analysis.

The evidence from epidemiological research on whether the efficacy of rituximab in treatment of refractory nephrotic syndrome (NS) is better than other agents is inconsistent. This meta-analysis aimed to assess the efficacy of rituximab in the treatment of NS compared with other immunosuppressive agents. Relevant literatures were identified and evaluated for quality before October 2019 through multiple search strategies on PubMed and EMBASE. Statistical evidence of the symmetry of the funnel plot obtained from Begg's test was indicated by Egger's linear regression and a sensitivity analysis identified heterogeneity. A fixed- or a random-effects model was applied to calculate the pooled SMDs and RRs. A total of 12 studies, involving 383 patients and 354 controls, were included. Compared with other agents, rituximab significantly improved complete remission both in children and adults [Overall: RR = 1.313, 95% CI = 1.170-1.475, P < 0.001; Adult: RR = 1.359, 95% CI = 1.053-1.753, P = 0.019 Children: RR = 1.354, 95% CI = 1.072-1.709, P < 0.001], and dramatically decreased the relapse rate in children [Overall: RR = 0.349, 95% CI = 0.166-0.732, P < 0.001; Children: RR = 0.286, 95% CI = 0.176-0.463, P < 0.001]. Rituximab might be a promising treatment for refractory NS. Compared with other agents, rituximab significantly improves the complete remission and decreased the relapse rate. However, to confirm the efficacy of rituximab in the treatment of refractory NS, more high-quality, large sample, and multicenter randomized controlled trials are needed.

Clinical effect of tripterygium glycosides combined with glucocorticoids in the treatment of refractory nephrotic syndrome patients: A systematic review and meta-analysis

The objective of this study is to evaluate the effectiveness and safety of Tripterygium glycosides combined with glucocorticoids for the treatment of refractory nephrotic syndrome (NS). Computer search of Chinese and English databases, including CNKI, VIP, Wan Fang Database, PubMed, Cochrane Library, Embase, and Sinomed, for randomized controlled trials (RCTs) of Tripterygium glycosides combined with glucocorticoids for refractory NS (RNS) was conducted. Meta-analysis was performed using RevMan5.3. Thirteen RCTs comprising 994 patients were included in the study. Tripterygium glycosides combined with glucocorticoids had a statistical significance on the effective rate (odds ratio [OR] =4.69, 95% confidence interval [CI] 3.29, 6.67, P

26 Cases of Intractable Membranous Nephropathy Glucocorticoid Combined Gilad Amine Clinical Curative Effect Observation

To study the clinical effect of glucocorticoid combined with thalidomide in the treatment of refractory nephrotic syndrome with membranous nephropathy. Methods: the pathological for membranous nephropathy of 26 patients with refractory nephrotic syndrome, glucocorticoid + gilad amine 50 mg 2 times/d, to turn the urine protein application again after 12 weeks after the reduction of 50 mg, l/d, maintain half year outage. The invalid was given a maximum of 24 weeks to stop the drug. The observation time was 24 weeks. Results: 24h urine protein decreased from 9.15 ±3.23 to 1.43±1.91 (P<0.01).Plasma albumin rose from 26.02 ± 6.75 to 35.57 ±4.02 (P<0.01). In most cases, the onset time was between 8 and 16 weeks, with a total relief of 30.77% in 24 weeks and 50.00% in partial relief, with a total effective rate of 80.77%.The main side effects are: rash, lethargy, fatigue, dizziness. No liver and kidney damage, bone marrow suppression. Conclusion: thalidomide combined with glucocorticoid is effective in the treatment of membranous nephropathy, with mild side effects, which provides a new way for the treatment of refractory membranous nephropathy.

Significance of acute kidney injury biomarkers in the treatment of refractory nephrotic syndrome with calcineurin inhibitors

Objective To investigate the significance of acute kidney injury biomarkers with calcineurin inhi-bitors(CNI) related nephrotoxicity in the treatment of refractory nephritic syndrome. Methods Ninety-two patients were included with 59 males and 33 females with average age of (5.67±3.65) years old, who were diagnosed with nephrotic syndrome at Shanghai Children′s Hospital from March 2014 to December 2015.66 patients including 44 males and 22 females with mean age of (4.97±3.52) were treated by steroid as the control group and 26 patients including 15 males and 11 females with mean age of (6.59±3.95) were treated by steroid combined with CsA and FK506 as the observation group.The blood, urine samples were collected before drug treatment (0 d) and very early stage of treatment (3 d), early stage (1 month), middle and late stage (3 months and 6 months) as the different observation time points.The change level of neutrophil gelatinase associated lipocalin(NGAL), kidney injury molecular-1(KIM-1), fibronectin(FN) and tumor necrosis factor-alpha(TNF-α) in serum and urine were detected at different time points to compare with biomarkers such as retinol-binding protein(RBP), N-acetyl-β-D-glucosamccharase(NAG) in urine. Results The serum NGAL(sNAGL)level was more obvious after 6 months of CNI treatment in the observation group than in the control group[(138.00±32.49) μg/L vs.(46.54±11.41) μg/L, t=2.115, P<0.05]; the level of urine TNF-α(uTNF-α) was higher obviously after 6 months of CNI treatment in the observation group than in the control group with significant differences[(2.35±0.78) pg/μmol vs.(0.75±0.36) pg/μmol, t=1.840, P<0.05]; the level of urine KIM-1(uKIM-1)was lower in the observation group than the control group after 3 months treatment of the CNI[(0.15±0.03) ng/μmol vs.(0.33±0.07) ng/μmol, t=-2.077, P<0.05); the level of urine NGAL(uNGAL) was lower in the observation group than the control group after 3 months treatment of the CNI [(0.09±0.03) ng/μmol vs.(0.23±0.04) ng/μmol, t=-2.959, P<0.05]. But the serum TNF-α(sTNF-α), urine FN(uFN), urine RBP(uRBP)and urine NAG(uNAG)did not show any significant change before and after the CNI treatment. Conclusions Compared with other acute kidney injury biomarkers (uNGAL, KIM-1, FN, RBP, and NAG), sNAGL and uTNF-α may be more sensitive to the early evaluation of CNI related nephrotoxicity.The occurrence of CNI related kidney injury shall be watched out at the beginning of 6-month of CNI treatment. Key words: Calcineurin inhibitors; Kidney injury; Neutrophil gelatinize-associated lipocalin; Kidney injury molecule-1; Fibronectin; Tumor necrosis factor-alpha

Efficacy of leflunomide combined with prednisone in the treatment of refractory nephrotic syndrome

Objective: To assess the safety and clinical efficacy of leflunomide (LEF) and prednisone on refractory nephrotic syndrome (RNS).Methods: A total of 52 patients with RNS were treated for 24 weeks between 2010 and 2014 in our hospital. In the treated group, 26 patients were treated with LEF and prednisone, and, in the control group, 26 patients were treated with cyclophosphamide (CTX) and prednisone. During the treatment, 24 h urinary protein excretion and the serum levels of albumin and cholesterol, and kidney function were assayed before and after the therapy. Adverse reactions during treatment were recorded.Results: In the LEF group, the medication was markedly effective in eight cases and effective in nine cases; the total efficacy rate was 65.30%. In the CTX group, the treatment was markedly effective in six cases and effective in nine cases; the total efficacy rate was 57%. There were no significant differences between the results of the total efficacy rate (p > .05). The 24 h urinary protein excretion and serum cholesterol levels in both groups decreased after therapy and the serum levels of albumin in both groups increased after therapy. There were significant differences between the results for the 24 h urinary protein excretion, serum levels of albumin and cholesterol in the two groups (p < .05). The treatments were well tolerated in both groups.Conclusion: LEF combined with prednisone has a certain efficacy on the RNS and displays few adverse reactions. A large-sample, randomized double-blind controlled study and long-term follow-up are needed to verify the efficacy of LEF combined with prednisone.

The clinical application and mechanism of tacrolimus in children with kidney diseases

Immune factor is one of the main mechanism of children glomerular diseases. Tacrolimus has a strong and effective immunosuppressive action comparing with CsA. In recent years,the curative effect of tacrolimus in the treatment of children with kidney disease has attracted doctors attention. Tacrolimus in the treatment for refractory nephrotic syndrome （ steroid-dependent nephrotic syndrome, steroid-resistent nephrotic syndrome and the frequent recurrence of glomerular syndrome） has obtained the good effect. This article reviews the application of tacrolimus in nephrotic syndrome,focal segmental glomerular sclerosis,mesangial proliferative glomerulonephritis,membranous nephropathy,lupus nephritis（ LN） in the children with kidney disease. Key words: Tacrolimus; Children; Kidney disease

Efficacy and Safety of Rituximab in Children with Refractory Nephrotic Syndrome; A Multicenter Clinical Trial

Objectives Rituximab (RTX), anti-CD20 monoclonal antibody, has been proposed as a rescue therapy for refractory nephrotic syndrome (NS) on the basis of favorable clinical observations. While reported efficacy of RTX on refractory RTX is promising, the long-term effect obtained from randomized clinical trial is limited, let alone the long-term safety profile of RTX in these patients. To obtain solid evidence of efficacy and safety of this medication, we conducted a clinical trial to evaluate the efficacy and safety of RTX in children with refractory NS. Here we report the interim result. Methods A multicenter open-label trial was performed in Korean pediatric patients, a single-arm study for steroid and calcineurin inhibitor (CNI) resistant (resistant NS, RNS), and a randomized controlled trial for steroid and CNI-dependent NS (dependent NS, DNS) patients. Eight major centers of Korea participated in this trial. Patients received a single dose of intravenous RTX (375 mg/m 2 ) and efficacy was monitored by clinical response and CD19 cell count. Primary end point was rate of remission achievement for RNS and maintenance of remission for DNS at 6 months after treatment. Steroid and CNI were slowly tapered as scheduled if remission was achieved. Results Nineteen patients (mean age 9.2±4.7 years) with RNS were enrolled and seven patients achieved complete remission after RTX treatment (remission rate 36.8%). Fifty-three children (mean age 13.0±4.9 years) with DNS were included and randomized to standard treatment or RTX (2:1). At six months after treatment, the remission rates were 77.1% in RTX arm (n=35) and 38.9% in standard therapy arm (n=18). The mean durations of remission maintenance were 5.2 months under slow-tapering standard therapy arm and undetermined in RTX arm. Twenty four patients (44.4% of 54 patients) experienced mild and transient infusion reaction during RTX administration. However, no serious side effect was observed. Conclusions In this interim analysis of clinical trial to evaluate the efficacy and safety of RTX in children with refractory NS, RTX treatment for refractory NS was safe and effective, especially in patients with DNS.

Efficacy of rituximab therapy in children with refractory nephrotic syndrome: a prospective observational study in Shanghai

Idiopathic nephrotic syndrome is the most common glomerular disease in children. This study was undertaken to observe the efficacy and side-effects of rituximab (RTX) in treating children with different types of refractory primary nephrotic syndrome. Twelve patients with steroid dependent nephrotic syndrome (SDNS), frequently relapsing nephritic syndrome (FRNS), and steroid resistant nephrotic syndrome (SRNS) were enrolled in our study. There were obvious drug side-effects, and proteinuria remained difficult to control. RTX was administered at a dose of 375 mg/m(2) body surface area, once or twice weekly. The male to female ratio was 3:1, and the onset age was 1.6-8.9 years. There were 9 patients with steroid sensitive nephrotic syndrome (SDNS or FRNS), and 3 patients with SRNS. There were 7 patients with minimal change disease (MCD), 3 patients with focal segmental glomerular sclerosis (FSGS), 1 with focal proliferative glomerulonephritis, and 1 without renal biopsy. The total effective treatment rate of RTX was 91.67%, and for 77.78% of the patients, steroid dosage could be reduced. Six months before and after RTX infusion, the mean steroid dosage was significantly decreased (P=0.014) and the recurrence number was significantly reduced (P<0.001). The results were better in MCD patients than in FSGS patients (P=0.045). There was no significant difference between FRNS/SDNS and SRNS patients (P=0.175). During RTX administration, 3 patients developed skin rashes, 1 developed hypotension, and 1 developed a fever. One patient experienced a persistent decrease in serum immunoglobulin level but without serious infection. RTX was effective in the treatment of refractory nephrotic syndrome, and it could significantly reduce the use of steroid and immunosuppressants.

Cyclosporine A for the treatment of refractory nephrotic syndrome with renal dysfunction

Cyclosporine A (CsA) is an immunosuppressant agent and is utilized as a second-line drug therapy for refractory nephrotic syndrome (RNS). In general, the use of CsA is strictly controlled in patients with an estimated glomerular filtration rate (eGFR) <30–40 ml/min/1.73 m2, and little is known about the safety and efficacy of CsA treatment in patients with RNS complicated by renal dysfunction. In the present study, the clinical data of 10 patients with RNS and renal dysfunction, who received CsA treatment between 2000 and 2009 in the Kidney Institute of PLA, were reviewed retrospectively. Pathologically, these patients included six cases with minimal change, two cases of diffuse mesangial proliferation and two cases of focal segmental glomerulosclerosis. Six months subsequent to the initiation of the CsA treatment, six patients achieved complete remission, two patients achieved remarkable remission and two patients achieved partial remission. Renal function was improved in all patients as represented by the improvement in the eGFR (28.6±3.8 ml/min/1.73 m2 prior to treatment versus 99.3±21.9 ml/min/1.73 m2 6 months subsequent to treatment). Few adverse CsA-related events were observed. These results suggest that renal dysfunction is not an absolute contraindication for CsA treatment in patients with RNS. The use of CsA is safe and efficacious and may, in certain cases, improve renal function in patients with RNS and renal impairment.

Observation on curative effects of leflunomide combined with glucocorticoids in the treatment of refractory nephrotic syndrome

Objective To investigate the efficacy of leflunomide combined with glucocorticoids in the treatment of refractory nephrotic syndrome.Methods In our hospital from January 2009 to January 2012,we selected 80 patients with renal biopsy diagnosis of refractory nephrotic syndrome as research subjects,according to different treatment they were divided into observation group and control group,40 cases in each group,and two groups were treated with oral prednisone,the observation group on the basis of the prednisone treatment was given leflunomide treatment,the efficacy was compared between two groups,and then observed 24 h urinary protein,serum albumin (ALB),serum creatinine (Scr) and blood urea nitrogen (BUN) changes after treatment of 4 weeks,12 weeks and 24 weeks,and recorded adverse reactions during treatment.Results The patients of two groups after treatment of 24 weeks,efficacy evaluation showed that the rote of complete remission of the observation group and control group a significant response rate,partial response rate and the total effective rate were compared between the two groups with no statistical significant differenee (P＞0.05).After treatment for 4 weeks,compared with those before treatment,24 h urinary protein,Scr were significandy lower,serum albumin was significantly higher,the difference was staistically significant (P＜0.05); BUN of the observation group and control group patients decreased significandy after treatment for 12 weeks,respectively,the difference was significant (P＜0.05); after treatment for 24 weeks,the above indicators,compared with those after treatment of 12 weeks,showed the significant difference (P＜0.05),and observation group improved more significantly than control group (P＜0.05).Conclusion Leflunomide combined hormone treatment of refractory nephrotic syndrome is safe and effective,with less adverse reaction,which is worthy of wider promotion and application,but tbe study did not extend the course of clinical observation in alleviating cases,therefore,it is recommended that its long-term efficacy,long-term prognosis and adverse reaction remains to be exploted by further in-depth research. Key words: Refractory nephrotic syndrome; Leflunomide; Glucocorticoids