The long-term results of pediatric patients with primary focal and segmental glomerulosclerosis

Focal and segmental glomerulosclerosis (FSGS) is a major cause of idiopathic steroid-resistant nephrotic syndrome (SRNS) and end-stage renal disease (ESRD). In this retrospective study, we report on 34 pediatric patients with FSGS who were diagnosed and treated from 1992 to 2006. The mean age at onset was 6.3 + or - 4.3 years. All patients had nephrotic-range proteinuria. Microscopic hematuria was seen in three patients and hypertension was seen in 15 patients at presentation. All patients were treated with steroids (oral and/or methylprednisolone), while 23 patients received cytotoxic therapy in addition. The mean follow-up period was 8.6 + or - 3.3 years at the end of which, 59% of patients achieved complete or partial remission, 20.5% continued to have active renal disease while 20.5% of the patients developed CKD. Our study suggests that most of the patients with FSGS progress to renal insufficiency. Steroid therapy increases the chances of remission and preserves renal function in patients with sporadic primary FSGS.
    • "Focal segmental glomerulosclerosis (FSGS) manifests with heavy proteinuria in association with focal, but progressive, glomerular sclerosis in the kidney123 . The frequency of endstage renal disease in patients with FSGS was found to be as high as 78% in long-term follow-up studies [4,5]. Although corticosteroids and other immunomodulatory agents are commonly used to treat these patients [6,7], they result in an unsatisfactory outcome in terms of progression of renal inflammation and fibrosis [8,9] and have various side-effects [10,11]. "
    [Show abstract] [Hide abstract] ABSTRACT: The pathogenesis of focal segmental glomerulosclerosis (FSGS) is considered to be associated with oxidative stress, mononuclear leukocyte recruitment and infiltration, and matrix production and/or matrix degradation, although the exact etiology and pathogenic pathways remain to be determined. Establishment of a pathogenesis-based therapeutic strategy for the disease is clinically warranted. Citral (3,7-dimethyl-2,6-octadienal), a major active compound in Litseacubeba, a traditional Chinese herbal medicine, can inhibit oxidant activity, macrophage and NF-κB activation. In the present study, first, we used a mouse model of FSGS with the features of glomerular epithelial hyperplasia lesions (EPHLs), a key histopathology index of progression of FSGS, peri-glomerular inflammation, and progressive glomerular hyalinosis/sclerosis. When treated with citral for 28 consecutive days at a daily dose of 200 mg/kg of body weight by gavage, the FSGS mice showed greatly reduced EPHLs, glomerular hyalinosis/sclerosis and peri-glomerular mononuclear leukocyte infiltration, suggesting that citral may be renoprotective for FSGS and act by inhibiting oxidative stress and apoptosis and early activating the Nrf2 pathway. Meanwhile, a macrophage model involved in anti-oxidative and anti-inflammatory activities was employed and confirmed the beneficial effects of citral on the FSGS model.
    Full-text · Article · Sep 2013
    • "A study by Chang et al showed that age of beyond 8 years at onset of NS is associated with a higher incidence of hypertension, hematuria, and progression to ESRD.19 Mekahli et al reported that an age of more than 10 years at NS onset was the only independent predictor of ESRD.17 Some studies focus on histopathology, and FSGS is generally believed to carry the worst prognosis.20 FSGS accounts for only 10% of INS in children,1,2 but its frequency in different studies ranges from 7% to 42% based on different criteria considered for renal biopsy.7,13,17,19,21 "
    [Show abstract] [Hide abstract] ABSTRACT: Characteristics of nephrotic syndrome (NS) in children varies in different geographical areas based on genetic and environmental factors. The aim of this study is to evaluate the steroid response pattern and outcome of idiopathic NS (INS) in a pediatric referral hospital in northwest Iran. Medical records of all admitted children under 14 years of age with INS in the Children's Hospital of Tabriz, Iran, from 1999 to 2010 were studied retrospectively. Demographics, pattern of response to medications, recurrence rate, histopathology, and outcome were documented. A total of 165 patients with INS, with a mean age of 4.98 ± 2.61 years were studied. Male to female ratio was 2:1. Duration of follow-up was 5.36 ± 2.2 years (1-10 years). A total of 124 patients (75.2%) responded to steroids, and 41 patients (24.8%) were steroid resistant. Frequency of hematuria (P = 0.01) and steroid resistance (P = 0.005) in girls was significantly higher than boys. Patients with steroid resistance had a higher frequency of hematuria (P = 0.001) and a higher mean age (P = 0.017) in comparison with steroid responders. Renal biopsy carried out in 49 patients (29.7%) revealed minimal change in NS in 20 (40.8%), focal segmental glomerulosclerosis in 16 (32.7%), and mesangial proliferation in 11 (22.5%) patients. Twenty-two steroid resistant patients (13%) achieved remission with other immunosupressives. Nineteen patients (11.5%) were resistant to all treatment modalities; of these, nine (5.4%) progressed to end-stage renal disease, and 10 (6%) continued nephrotic range proteinuria. Seven patients (4.2%) died. Of the 146 patients who achieved remission with any one of the treatment modalities, 91 patients (62.3%) experienced at least one recurrence episode, 15 patients (10.3%) were frequent relapsers, and 12 patients (8.2%) were steroid dependent. Higher age at onset of NS was associated with lower relapse rate (P = 0.04). Demographics, histological features, and outcome of INS in our area were similar to western countries. In the present study, risk of steroid resistance was higher in girls than boys.
    Article · May 2011
    • "The use of cytotoxic drugs, in association with steroids, improves the remission rate in SRNS123. However, a significant proportion of patients fail to achieve remission and progress to chronic renal failure [4, 5]. Furthermore, the potential toxicity of these drugs represents a concern that has triggered the search for other treatments. "
    [Show abstract] [Hide abstract] ABSTRACT: Rituximab has been used over the last decade as a rescue therapy for refractory cases of nephrotic syndrome (NS). Here we report the use of rituximab in four children with idiopathic steroid-resistant nephrotic syndrome (SRNS) with various histological backgrounds (two cases with focal segmental glomerulosclerosis, one case with IgM nephropathy, and one case with minimal change disease), who failed to respond to other immunsuppressions. Their median age (range) was 10 (8-11) years. NPHS2 genetic mutation was negative in all of them. All patients received a single dose of rituximab (375 mg/m(2)) and achieved complete B cell depletion as CD19 was <1% for 3 months following rituximab infusion. Only one patient achieved non-sustained remission as he relapsed after 4 months despite zero CD19 level. Patients received no further doses of rituximab as B cell was depleted in the peripheral circulation. We conclude that a single dose of rituximab was not effective in inducing sustained remission in children with idiopathic SRNS, despite complete B cell depletion in the peripheral circulation. Further doses might be indicated to deplete non-circulating B cells.
    Full-text · Article · May 2011
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