Relative safety of steroid sparing agents in frequently relapsing, steroid dependent and steroid resistant nephrotic syndrome in pediatric patients

Background: In patients with frequently relapsing nephrotic syndrome (FRNS), steroid-dependent nephrotic syndrome (SDNS) and steroid resistant nephrotic syndrome (SRNS) steroids are either used for prolonged period of time or ineffective. To reduce the degree of steroid dependency and avoid steroid toxicity, several immunosuppressive steroid sparing agents (SPAs) have been proposed to treat these children. The present study tried to study the relative safety of most commonly steroid sparing agent in such children.Methods: A multi-centred, prospective observational study was conducted in paediatric nephrology OPD of two tertiary care hospitals in Kolkata over a period of 24 months. All consecutive children with diagnosed FRNS, SDNS and SRNS who were started on steroid sparing agents were enrolled and followed up for at least 6 months. Records of clinical examination, laboratory tests were collected and measured at the baseline and regular intervals. Safety parameters were noted and statistically analysed.Results: A total 110 patients were screened, examined and enrolled. Levamisole, cyclophosphamide and MMF were commonly used SPAs. Of the two tertiary care hospitals, all the patients of FRNS and SDNS were started with levamisole and SRNS with cyclophosphamide in one set-up, while in the other hospital some SDNS patients were started with cyclophosphamide and SRNS with MMF but without clinically significant outcomes. In comparison with few minor adverse events in MMF group, some serious adverse events were documented in the both cyclophosphamide and levamisole groups.Conclusions: Levamisole being a very efficacious, safe and easily affordable drug, should be used as an initial first line SPA in treating FRNS and SDNS children. The side effect profiles of levamisole and MMF are much more patient friendly.

Application of rituximab in children with primary nephrotic syndrome / 医学研究生学报

Childhood primary nephrotic syndrome (PNS) is a challenging and persistent renal disorder. Corticosteroids is the first-line drug for the treatment of PNS. To reduce the side effects caused by the accumulation of corticosteroids dose and to maintain the remission state of the disease, immunosuppressants are applied to the treatment of PNS. However, many children with PNS still cannot get remission. Rituximab (RTX) is a novel immunosuppressive agent. In recent years, many studies have reported the treatment of PNS in children with RTX. This review analyzes the mechanism, course of treatment, dose, efficacy, and safety of RTX in the treatment of children with PNS.

Efficacy of Tacrolimus in Treating Nephrotic Syndrome Children.

Nephrotic Syndrome (NS) is primarily a pediatric disorder, common in pre-schooler and school aged children. Immunosuppresive drugs like prednisolone, cyclophosphamide, cyclosporine A (CsA) has been the main treatment regimen in the management of Nephrotic syndrome. This has remain still the same therapy which is not satisfactory in the management of nephrotic syndrome children. The management of children with idiopathic Steroid-Resistant Nephrotic Syndrome (SRNS) and Steroid-Dependent Nephrotic Syndrome (SDNS) are difficult to treat but there is no consensus on the most appropriate treatment therapy. Pneumonia and urinary tract infection are also a challenge in the management of NS. The main goal of treatment is complete or partial remission of proteinuria, which is the most important marker of long term outcome. Calcineurin inhibitors (CNIs) are used to avoid steroid toxicity in children with NS. There are limited data on the relative efficacy and safety of calcineurin inhibitors and alkylating agents for NS in children. There are different immunosuppressant drugs but tacrolimus can be used in the treatment of childhood NS which is less expensive, have less cosmetic side effects and easy to administered. In this review we discuss the safety and efficacy of tacrolimus, a new drug which can be administered orally as a twice daily dose in the management of childhood NS. Some study suggests that application of tacrolimus can be a new turning point for the treatment of nephrotic syndrome.

Efficacy and Safety of Mycophenolate Mofetil in Children with Steroid Dependent Nephrotic Syndrome

PURPOSE: Steroid dependent nephrotic syndrome (SDNS) is a chronic illness in childhood hard to treat. Steroid sparing drugs are often used, because long-term steroid therapy can cause severe side effects. We studied to compare efficacy between MMF and other drugs including cyclosporine and levamisole. METHODS: This study was performed retrospectively on patients with SDNS, who were treated at Pusan National University Children's hospital. MMF group included 11 patients who were treated with MMF for at least six months between June 2012 and July 2014. As control groups, cyclosporine group (n=15) and levamisole group (n=18) included patients treated between January 2008 and July 2014. Number of relapse was analyzed in patients treated more than six months, and relapse free for one year was analyzed in patients treated more than one year. RESULTS: In MMF group, ten were boys and mean age at onset was 5.8 years. Mean age at starting of MMF was 8.6 years. Number of relapse in MMF group was reduced significantly after treatment from 3.4 /year to 0.2 /year (P=0.003). There was no significant difference in number of relapse among groups (MMF: 0.2 /year, cyclosporine: 0.5 /year, levamisole: 0.5 /year). Comparing the early relapse within six months after treatment levamisole group was significantly higher than the other two groups (P=0.04). CONCLUSIONS: MMF which is used in SDNS significantly reduced the relapse and side effects were rare. In addition, MMF did not show any significant difference in comparison with the other two groups in number of relapse and relapse free for one year.

Disease Course in Steroid Sensitive Nephrotic Syndrome.

Objective: To review the disease course in patients with steroid sensitive nephrotic syndrome (SSNS) and the factors that determine outcome Design: Retrospective, analytical Setting: Pediatric Nephrology Clinic at referral center in North India Participants/patients: All patients with SSNS evaluated between 1990 and 2005 Intervention: None Main outcome measures: Disease course, in patients with at least 1-yr follow up, was categorized as none or infrequent relapses (IFR), frequent relapses or steroid dependence (FR), and late resistance. Details on complications and therapy with alternative agents were recorded. Results: Records of 2603 patients (74.8% boys) were reviewed. The mean age at onset of illness and at evaluation was 49.7±34.6 R E S E A R C H P A P E R INDIAN PEDIATRICS 881 VOLUME 49__NOVEMBER 16, 2012 and 67.5±37.9 months respectively. The disease course at 1-yr (n=1071) was categorized as IFR in 37.4%, FR in 56.8% and late resistance in 5.9%. During follow up, 224 patients had 249 episodes of serious infections. Alternative medications for frequent relapses (n=501; 46.8%) were chiefly cyclophosphamide and levamisole. Compared to IFR, patients with FR were younger (54.9±36.0 vs. 43.3±31.4 months), fewer had received adequate (≥8 weeks) initial treatment (86.8% vs. 81.7%) and had shorter initial remission (7.5±8.6 vs. 3.1±4.8 months) (all P<0.001). At follow up of 56.0±42.6 months, 77.3% patients were in remission or had IFR, and 17.3% had FR. Conclusions: A high proportion of patients with SSNS show frequent relapses, risk factors for which were an early age at onset, inadequate initial therapy and an early relapse.

Mutations in NPHS2 Gene in A Child with Steroid-Dependent Nephrotic Syndrome / 实用儿科临床杂志

T were also detected in the controls.Conclusion Nephrotic syndrome may be associated with NPHS2 identified in children.

A Case of C1q Nephropathy in Steroid-Dependent Nephrotic Syndrome

C1q nephropathy is an immune complex glomerulonephritis defined by the presence of mesangial C1q deposits in immunofluorescence microscopy and electron dense deposits on electron microscopy. It was described as a distinct disease entity in 1985 by Jennette and Hipp. Thirty four cases were reported in the literature but there has been no pediatric case reported in Korea yet. It commonly presents with steroid-resistent nephrotic syndrome in older children and young adults, and occasionally nephritic-nephrotic syndrome or rapidly progressive glomerulonephritis. We report a case of C1q nephropathy in a 23-month-old girl with steroid-dependent nephrotic syndrome.

The Effect of Levamisole in Steroid-Dependent Nephrotic Syndrome in Children

PURPOSE: Long-term use of steroid, cyclophosphamide and cyclosporin, which are frequently used in the therapy of SDNS, might cause severe side effects. Recently, the immune-modulator levamisole has been tried as a substitute therapy and it has been reported as a method with less side effects and more effectiveness. We started this research in order to observe the effects of levamisole and compare it to other therapy results. PATIENTS AND METHODS: We chose 16 steroid dependent nephrotic syndrome children, those who had shown frequent relapse during the immunocompromised therapy period. Mean age was 9.1+/-.4 years in children and the male to female ratio was 15:1. All of subjects were diagonized with MCNS and had received cyclophosphamide or cyclosporin before receiving levamisole. Levamisole at a dose of 2.5mg/kg was used every other day for 1 year and the relapse rate was observed. RESULTS: On average of 14 days after treatment, complete remission was visible in all of the children, and the relapse percentage was 50%, which represents 8 children, while remaining 8 children representing 50% of the cases showed no relapse during treatment. During the levamisole therapy period, the average relapse rate was reduced significantly from 2.18+/-.9/year to 0.77+/-.9/year(p=0.027). Also the average relapse rate after the therapy was reduced to 1.34+/-.1/year, which was a significant level compared to the level before treatment(p=0.003). There was no significant difference in terms of duration of remission maintenance. Duration of remission maintenance showed an average of 12.2+/-.1 months before the use of levamisole, but it was also 10.1+/-.9 month after therapy. No other side effects such as leukopenia, skin disease and other clinically significant symptoms appeared at all during therapy. CONCLUSION: The long-term medication of levamisole for the therapy of SDNS children is thought to be able to maintain stable remission by reducing the relapse frequency without causing severe side effects. Further study with a broader range of subjects is required to eluccidate the long-term effects of this treatment.

A Case of Focal Glomerular Sclerosis (Glomeruloscrelosis) Treated with Bunsho-to / 日本東洋医学雑誌

We report a case of a patient with steroid-dependent nephrotic syndrome, who achieved complete remission with a combination of steroid therapy and Bunsho-to. The patient was a 27-year-old female who became aware of edema, and was diagnosed as suffering from focal glomerular sclerosis (glomerulosclerosis) with nephrotic syndrome in November 1992. She responded to steroid therapy, but nephrotic syndrome relapsed frequently after the repeated reduction of steroids. In July 1995, she came to our hospital, and was diagnosed as having a recurrence of nephrotic syndrome. Although the combination therapy of steroid and Kampo formulas, Shinbu-to or Shimotsu-to and/or Keigairengyo-to, was effective, an exacerbation of nephrotic syndrome occurred after steroid therapy was discontinued, in July 1997. The prescription was changed to Bunsho-to, and steroid therapy was re-initiated with 10mg of prednisolone daily. As a result, she achieved complete remission. The steroid therapy could be discontinued in July 1999, and now she has taken Bunsho-to only for 18 months. But the complete remission of nephrotic syndrome has been maintained.

Levamisole-Induced Reversible Agranulocytosis in Children with Steroid Dependent Nephrotic Syndrome

Levamisole has been used for nephrotic syndrome due to its immunostimulating, immunomodulating, and steroid-sparing effects. Agranulocytosis, a serious side effect of levamisole, was rare and mostly associated with autoimmune disease, neoplastic disease and HLA B27 except one case in a nephrotic syndrome who was treated with high-dose(5mg/kg QOD) levamisole. This 15 year-old girl with steroid dependent nephrotic syndrome, who was negative for HLA B27, was treated with the usual recommended dose of levamisole(2.5mg/kg QOD). She developed agranulocytosis after 5 weeks of therapy and completely recovered in 11 days after discontinuation of levamisole.

Therapeutic Effects of Cytotoxic agents (cyclophosphamide and chlorambucil), Cyclosporine and Levamisole in Children with Steroid-dependent Nephrotic Syndrome / 대한신장학회잡지

Prolonged administration of steroid in children with steroid-dependent nephrotic syndrome can cause serious complications including growth failure, and various alternative treatments have been used for these children to alleviate steroid-induced complications and to achieve long-lasting remission. Present study was undertaken to compare the therapeutic efficacy of cytotoxic agents (cyclophosphamide and chlorambucil), cyclosporine and levamisole in 88 children with steroid-dependent mininal-change nephrotic syndrome, who have been followed-up in Pediatric Department, Kyungpook National University Hospital from 1985 to 1995. Cyclophosphamide and chlorambucil were given for 8 weeks (cyclophosphamide in 36 and chlorambucil in 13 cases) or 12 weeks (cyclophosphamide in 34 and chlorambucil in 12 cases), and cyclosporine (3-5mg/kg/day) and levamisole (2-2.5mg/kg alternate day) were given for 6-12 months. And the results were as follows ; Results of cytotoxic therapy ; At the end of the 1st year, remission rate with 12 wks course of cyclophosphamide(53%) was better than with 12 wks course of chlorambucil(33%) or 8 wks course of either drugs. However, at the end of the 2nd year, no difference was noted in remission rate between 12 wk course of cyclophosphamide(19%) and chlorambucil(17%). Results of cyclosporine therapy ; Out of 44 cases, 28(64%) showed sustain-ed remission, 8(18%) relapse with decreased frequency and steroid-sparing effect, and 8 no therapeutic effects. During treatment period, BUN, creatinine and blood pressure were remained in normal ranges. Remission rates with cyclosporine alone therapy without steroid in cyclosporine-responsive children were 83%, 83%, 57% and 43% at 2, 4, 6 and 8 months, respectively. Results of levamisole therapy ; Out of 16 cases, 8 (50%) showed sustained remission, 5(31%) relapse with decreased frequency and steroid-sparing effect, and 3 no therapeutic effects. In one case, transient neutropenia was observed without serious sequelae. Remission rate with levamisole alone therapy without steroid in levamisole-responsive children were 88%, 85%, 67% and 44% at 2, 4, 6 and 8 months, respectively. In conclusion, present study indicates that 12 weeks course of cyclohospha-mide or chlorambucil seems to be the most effective therapy for inducing long-lasting remission in steroid-dependent nephrotic children. And long-term use of cyclosporine or levamisole can also be used quite effectively in achieving prolonged remission and steroid-sparing effects without serious side effects.