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OBJECTIVES@#To study the efficacy and safety of repeated application of rituximab (RTX) at a low dose (200 mg/m2) versus the recommended dose (375 mg/m2) for remission maintenance in frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).@*METHODS@#A randomized controlled trial was conducted for 29 children with FRNS/SDNS who received systemic treatment in the Department of Nephrology, Anhui Provincial Children's Hospital, from September 2020 to December 2021. These children were divided into a recommended dose group (n=14) and a low dose group (n=15) using a random number table. The two groups were compared in terms of general characteristics, changes in CD19 expression after RTX treatment, number of relapses, glucocorticoid dose, adverse reactions of RTX, and hospital costs.@*RESULTS@#After RTX treatment, both the low dose group and the recommended dose group achieved B-lymphocyte depletion and had significant reductions in the number of relapses and glucocorticoid dose (P<0.05). The low dose group had a comparable clinical effect to the recommended dose group after RTX treatment (P>0.05), and the low dose group had a significant reduction in hospital costs for the second, third, and fourth times of hospitalization (P<0.05). There were no serious adverse reactions in either group during RTX treatment and late follow-up, and there was no significant difference in adverse reactions between the two groups (P>0.05).@*CONCLUSIONS@#Repeated RTX treatment at a low dose has comparable clinical efficacy and safety to that at the recommended dose and can significantly reduce the number of FRNS/SDNS relapses and the amount of glucocorticoids used, with little adverse effect throughout the treatment cycle. Therefore, it holds promise for clinical application.
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Humans , Child , Nephrotic Syndrome/drug therapy , Rituximab/adverse effects , Glucocorticoids/adverse effects , Prospective Studies , Adaptor Proteins, Signal TransducingABSTRACT
Introduction: Childhood nephrotic syndrome has an incidence of 90–100 per million population of India. This study was conducted with the primary objective of studying the prevalence of different clinical variants of childhood nephrotic syndrome (new-onset steroid-sensitive nephrotic syndrome/infrequent relapsing nephrotic syndrome [IFRNS]/frequently relapsing nephrotic syndrome [FRNS]/steroid-dependent nephrotic syndrome [SDNS]/steroid-resistant nephrotic syndrome [SRNS]), while the secondary objectives were to estimate the prevalence of use of steroid-sparing drugs in those with FRNS and SDNS. Materials and Methods: A retrospective study of all patients referred to renal diseases clinic at Government Medical College, Jammu, was done. Records of 61 children of 1–18 years of age fulfilling the International Study of Kidney Disease in Children criteria for nephrotic syndrome attending to our nephrology clinic were reviewed over 1 year period. Standard definitions for new-onset nephrotic syndrome, IFRNS, FRNS, SDNS, and SRNS were used. Steroid-sparing drugs used were levamisole in FRNS and low-dose SDNS whereas cyclophosphamide, mycophenolate mofetil (MMF), and tacrolimus in high-dose SDNS. Results: Among nephrotic syndrome, patients mean age of presentation was 5.95 years, with M: F ratio of 1.77:1. Infrequent relapsers (27.9%) were the most prevalent clinical variant followed by steroid-dependent nephrotic syndrome (24.6%) and new-onset nephrotic syndrome (21.3%). Prednisolone alone was successful in achieving remission in 50.8% of total cases and less commonly involving use of other immunosuppressants with prednisolone such as levamisole (23%), cyclophosphamide (9.8%), and tacrolimus in (3.3%). However, prednisolone in combination with cyclophosphamide and then MMF was used in 14 (23%) in an aim to achieve full remission, but full remission was achieved in 48 (78.7%). Conclusion: In the present study, clinical profile of children with nephrotic syndrome was concordant with typical nephrotic syndrome in children. Pattern of nephrotic syndrome differs in our population in terms of increased number with SDNS and response to treatment did not differ significantly from other studies.
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Dependence is an uncommon, but potentially sinister complication of corticosteroid therapy. prednisolone was the most frequently implicated corticosteroid in steroid dependence. Here we report a rare case of oral prednisolone dependence in middle aged man who had chronic asthma.
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Objective Few researches have been reported on the gene methylation in children with steroid-sensitive nephrot-ic syndrome (SSNS) or steroid-dependent nephrotic syndrome (SDNS).This study aimed to investigate the possible pathogenesis and therapeutic target of SSNS and SDNS by screening differentially methylated genes ( DMGs) and bioinformatic analysis using DNA meth-ylation microarray. Methods This study included 3 hospitalized children with SSNS and another 4 with SDNS, all treated with full dose of prednisone ( 2 mg per kilogram of the body weight per day or 60 mg per m2 per day).Negative urine protein was achieved within 4 weeks in the former group , while the latter , though sensitive to hor-monal therapy , relapsed within 2 weeks after drug withdrawal or dose reduction .DNA was extracted from the peripheral blood of the patients in both groups for screening DMGs and bioinformatic analysis using DNA methylation microarray . Results Compared with the patients with SSNS, 318 DMGs were found in the SDNS group , among which 193 were hypermethylated and the other 125 hypomethylated .These abnormal genes were mainly located in the open reading frame of DNA and the CpG island region .DMGs were mainly involved in Rho guanyl-nucleotide exchange factor activity , nucleoside-triphosphatase regulator activity , GTPase activator activity , and other molecular functions .The biological processes were chiefly associ-ated with the regulation of the generation of precursor metabolites and energy , antigen processing and presentation , regulation of Rho and Ras protein signal transduction , lamellipodium assembly , regeneration , and other biological processes .The cell composition was mainly related to MHC protein complexes , perichromatin fibrils , and the MHC class I protein complex .Analysis of the KEGG signaling pathway showed that DMGs participated in 9 signaling pathways , involving type I diabetes , starch and sucrose metabolism , allograft re-jection, autoimmune thyroid disease , and others. Conclusion The heterogeneity of methylation is widespread in children with SDNS and may be one of the causes of steroid dependence , which has provided a basis for searching for potential therapeutic targets .
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Steroid withdrawal syndrome (SWS) following steroid dependence is becoming a common clinical condition. It may be associated with body image disorder. Though selective serotonin reuptake inhibitors (SSRIs) are found to be effective SWS associated depression, data for this clinical condition is limited. We present a case of SWS associated with body image disorder which improved with mirtazapine. Mirtazapine might be better option than SSRIs in this subgroup of patients for its noradrenergic property and better gastrointestinal profile. More research should explore its efficacy in this clinical condition.
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Humans , Body Dysmorphic Disorders , Depression , Selective Serotonin Reuptake InhibitorsABSTRACT
Objective To evaluate the efficacy of tacrolimus in patients with prednisone-dependent generalized myasthenia gravis (MG). Methods A total of 74 patients with prednisone-dependent generalized MG received either tacrolimus (FK506) (n=34) or azathioprine (n=40) for more than 12 months. The daily dosage and adverse reaction of tacrolimus or azathioprine used in these two groups were recorded, and the therapeutic effect of the drugs and the clinical scores of MG were evaluated and compared between the two groups before treatment and at 1, 3, 6 and 12 months after treatment. Results Compared with that of before treatment (18.2±9.1), clinical relative scores of MG decreased significantly in tacrolimus group at 1, 3, 6 and 12 months after its treatment (13.4±6.5, 10.7±4.6, 8.7±3.7 and 5.3±2.1, respectively) (P<0.01). While in azathioprine group, the significant differences in efficiency appeared only 6 and 12 months after azathioprine treatment (P<0.05). The total clinical efficacy (clinical relative score ≥25%) in tacrolimus group were 65.3%, 77.6%, 81.2% and 85.8%, respectively at 1, 3, 6 and 12 months after treatment, and it was significantly higher than that in azathioprine group (12.3%, 25.4%, 56.7% and 75.6%, respectively). Prednisone decrement rate in tacrolimus group was 8.8%, 32.4% and 70.6%, respectively at 3, 6 and 12 months after treatment, and the rate of prednisonerelated adverse effects decreased from 94.1% at baseline to 14.7% at the final visit (P<0.01). Conclusion The therapeutic effect of tacrolimus is clearly superior to that of azathioprine for the prednisone-dependent generalized MG patients, and it significantly reduces the dependence of patients on prednisone.
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Objective: To analyse the effectiveness and safety of cyclosporin A (CsA) in the treatment of steroid dependent nephrotic syndrome (SDNS) in childhood. Design: Prospective descriptive study Setting: Nephrotic Syndrome Clinic, Teaching Hospital Peradeniya, Sri Lanka Method: Children with SDNS who had normal renal function, relapsed while receiving over 1mg/kg prednisolone on alternate days and who had received at least one course of cyclophosphamide were recruited to the study over a period of 5 years. They were treated with CsA 3-5 mg/kg/day orally with a tapering dose of alternate day prednisolone. Statistical analysis was performed using paired t-test. Results: Over 5 years, 48 children who satisfied the inclusion criteria were recruited. CsA therapy was discontinued in two patients who had evidence of nephrotoxicity within 6 months of therapy. Forty six patients completed the study. Thirty one were male. The maintenance dose of prednisolone was tapered at least by 50% at 6 months of therapy in 38 (83%) patients. At the completion of 6 months of therapy, the mean serum cholesterol decreased from 396.96 mg/dl to 269.5 mg/dl (p<0.01) and the mean serum albumin increased from 21.1 mg/dl to 33.5 mg/dl (p<0.01). Hypertension was seen in 26 (57%) patients and hirsutism in 37 (80%). All patients had normal liver enzymes and opportunistic infections were not encountered. Conclusions: CsA treatment in combination with low-dose prednisolone is highly effective in maintaining complete remission in difficult SDNS in childhood. Reversible nephrotoxicity was seen in 4% of patients, hypertension in 57% and hirsutism in 80%.