scholarly journals The Mycophenolate Mofetil Therapy in Corticoresistent Idiopathic Focal Segmental Glomerulosclerosis

2020 ◽  
pp. 1-4
Author(s):  
Nereida Spahia ◽  
Merita Rroji ◽  
Myftar Barbullushi ◽  
Mauro Sasdelli
Keyword(s):  
Nephrotic Syndrome ◽  
Mycophenolate Mofetil ◽  
Kidney Function ◽  
Focal Segmental Glomerulosclerosis ◽  
Excretion Rate ◽  
Alternative Therapy ◽  
Calcineurin Inhibitors ◽  
Average Period ◽  
Urinary Proteins ◽  
Segmental Glomerulosclerosis

The Focal Segmental Glomerulosclerosis (FSGS) is one of the most frequent glomerular nephropathies affecting both children and adults. The aim of this study is the evaluation of the effects of Mycophenolate Mofetil (MMF) in Nephrotic Syndrome (NS) with biopsy proven Focal Segmental Glomerulosclerosis (FSGS) resistant to other therapies. We treated 20 patients, of which 12 males, with a median age of 39 years (ranging between 18 and 62 years), with Nephrotic Syndrome, all being resistant to or relapsing on steroid and immunosuppressive therapy. They were treated with MMF (1-2 g/day) and Methylprednisolone 0.5 mg/kg at alternate days for an average period of ten months (ranging between 3 and 13 months). Two patients discontinued treatment after three and five months respectively, for gastric intolerance. Another patient discontinued MMF after six months due to deterioration of kidney function. No significant differences were observed between pretreatment values and at the end of the treatment for plasma creatinine, Glomerular Filtration Rate (GFR), while the excretion rate of urinary proteins was significantly reduced from 7.68 ± 3.54 to 3.20 ± 2.92 g/day, (p<0.001). After MMF we observed a complete remission in two patients (10%), an incomplete remission in three patients (15%), a partial remission in six patients (30%), no response in eight patients (40%) and a worsening of kidney function in one patient (5%). It was concluded that in resistant Nephrotic Syndrome by FSGS, MMF can favor stable remission, preserving renal function and hence being considered as an alternative therapy to calcineurin inhibitors, but with lower toxicity.

scholarly journals Focal segmental glomerulosclerosis: challenges in definitions, pathogenesis and management

2017 ◽  
Vol 20 (1) ◽  
pp. 48-56
Author(s):  
John Feehally
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Clinical Manifestations ◽  
Calcineurin Inhibitors ◽  
Spontaneous Remission ◽  
Glomerular Injury ◽  
Single Entity ◽  
Segmental Glomerulosclerosis ◽  
Pathological Subtype ◽  
Steroid Sensitive Nephrotic Syndrome

Focal segmental glomerulosclerosis (FSGS) is a well-defined pattern of glomerular injury identifiable on renal biopsy using light microscopy. FSGS is not a single entity and much information is needed to make a proper evaluation in each subject with the condition to identify the cause, prognosticate, and inform treatment choices. Categories of information required include: clinical presentation, responsiveness to steroids, pathological subtype, genetic background, and evidence for other adaptive, viral, and toxic causes. Primary FSGS describes a cohort of conditions identified by exclusion of known contributory causes, but does not represent a single entity. Clinical manifestations and outcomes of FSGS vary widely; they include asymptomatic proteinuria, cases of spontaneous remission, steroid-sensitive nephrotic syndrome, and nephrotic syndrome resistant to immune modulating therapy progressing to end-stage renal disease with recurrence after transplantation. Although immune modulating therapy (based notably on corticosteroids and calcineurin inhibitors) are widely used in primary FSGS, robust evidence of their efficacy remains scant.

Primary focal segmental glomerulosclerosis

2018 ◽  
Author(s):  
Alain Meyrier ◽  
Patrick Niaudet
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Remission Rate ◽  
Calcineurin Inhibitors ◽  
Steroid Treatment ◽  
High Dose ◽  
Glomerular Injury ◽  
Asian Patients ◽  
Segmental Glomerulosclerosis ◽  
Black Patients

The proportion of cases of primary focal segmental glomerulosclerosis responsive to treatment with corticosteroids is variable and depends on histological type, patient age and duration, and dose of steroid treatment, but overall complete remission rate is estimated at 20–25% in white and Asian patients, and lower in black patients. Partial response dependent on a high dose of steroids is common. Despite anxieties about nephrotoxicity, there may be justification for adding calcineurin inhibitors to control nephrotic syndrome if it is severe. Data for additional agents is not very encouraging. Plasma exchange appears to remove a circulating factor that causes proteinuria in focal segmental glomerulosclerosis, as illustrated by responses to this treatment when proteinuria recurs acutely after kidney transplantation. This is rarely pursued clinically except after transplantation, in advance of severe glomerular injury.

Modern pharmacological approaches to primary treatment nephrotic syndrome

2020 ◽  
Vol 24 (4) ◽  
pp. 9-20
Author(s):  
Ya. F. Zverev ◽  
A. Ya. Rykunova
Keyword(s):  
Nephrotic Syndrome ◽  
Monoclonal Antibodies ◽  
Mycophenolate Mofetil ◽  
Beneficial Effect ◽  
Pharmacological Activity ◽  
Glucocorticoid Receptors ◽  
Calcineurin Inhibitors ◽  
Mechanisms Of Action ◽  
Immune Mechanism ◽  
Immune Mechanisms

The review is devoted to the consideration of the most common drugs currently used in the treatment of primary nephrotic syndrome. Mechanisms of pharmacological activity of glucocorticosteroids, ACTH, calcineurin inhibitors cyclosporine A and tacrolimus, alkylating compounds cyclophosphamide and chlorambucil, mycophenolate mofetil, levamisole, abatacept, rituximab and a number of other recently created monoclonal antibodies. An attempt is made to separate the immune and non-immune mechanisms of action of the most common drugs, concerning both the impact on the immunogenetics of the noted diseases and the direct impact on the podocytes that provide permeability of the glomerular filtration barrier and the development of proteinuria. It is shown that the immune mechanisms of corticosteroids are caused by interaction with glucocorticoid receptors of lymphocytes, and nonimmune – with stimulation of the same receptors in podocytes. It was found that the activation of adrenocorticotropic hormone melanocortin receptors contributes to the beneficial effect of the drug in nephrotic syndrome. It is discussed that the immune mechanism of calcineurin inhibitors is provided by the suppression of tissue and humoral immunity, and the non-immune mechanism is largely due to the preservation of the activity of podocyte proteins such as synaptopodin and cofilin. Evidence is presented to show that the beneficial effect of rituximab in glomerulopathies is related to the interaction of the drug with the protein SMPDL-3b in lymphocytes and podocytes. The mechanisms of action of mycophenolate mofetil, inhibiting the activity of the enzyme inosine 5-monophosphate dehydrogenase, which causes the suppression of the synthesis of guanosine nucleotides in both lymphocytes and glomerular mesangium cells, are considered. It is emphasized that the effect of levamisole in nephrotic syndrome is probably associated with the normalization of the ratio of cytokines produced by various T-helpers, as well as with an increase in the expression and activity of glucocorticoid receptors. The mechanisms of pharmacological activity of a number of monoclonal antibodies, as well as galactose, the beneficial effect of which may be provided by binding to the supposed permeability factor produced by lymphocytes, are considered.

scholarly journals Clinical manifestations of focal segmental glomerulosclerosis in Japan from the Japan Renal Biopsy Registry: age stratification and comparison with minimal change disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takaya Ozeki ◽  
Shoichi Maruyama ◽  
Toshiyuki Imasawa ◽  
Takehiko Kawaguchi ◽  
Hiroshi Kitamura ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Biopsy ◽  
Focal Segmental Glomerulosclerosis ◽  
Clinical Diagnosis ◽  
Clinical Characteristics ◽  
Minimal Change Disease ◽  
Multivariable Analysis ◽  
Laboratory Data ◽  
Minimal Change ◽  
Segmental Glomerulosclerosis

AbstractFocal segmental glomerulosclerosis (FSGS) is a serious condition leading to kidney failure. We aimed to investigate the clinical characteristics of FSGS and its differences compared with minimal change disease (MCD) using cross-sectional data from the Japan Renal Biopsy Registry. In Analysis 1, primary FSGS (n = 996) were stratified by age into three groups: pediatric (< 18 years), adult (18–64 years), and elderly (≥ 65 years), and clinical characteristics were compared. Clinical diagnosis of nephrotic syndrome (NS) was given to 73.5% (97/132) of the pediatric, 41.2% (256/622) of the adult, and 65.7% (159/242) of the elderly group. In Analysis 2, primary FSGS (n = 306) and MCD (n = 1303) whose clinical diagnosis was nephrotic syndrome (NS) and laboratory data were consistent with NS, were enrolled. Logistic regression analysis was conducted to elucidate the variables which can distinguish FSGS from MCD. On multivariable analysis, higher systolic blood pressure, higher serum albumin, lower eGFR, and presence of hematuria associated with FSGS. In Japanese nationwide registry, primary FSGS patients aged 18–64 years showed lower rate of NS than those in other ages. Among primary nephrotic cases, FSGS showed distinct clinical features from MCD.

MO294COMPARISON OF TIP AND CELLULAR VARIANT OF PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Nikola Zagorec ◽  
Ivica Horvatić ◽  
Dino Kasumović ◽  
Petar Šenjug ◽  
Matija Horaček ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Clinical Features ◽  
Remission Rate ◽  
Prognostic Significance ◽  
European Population ◽  
University Hospital ◽  
Outcome Analysis ◽  
Laboratory Findings ◽  
Segmental Glomerulosclerosis

Abstract Background and Aims After membranous nephropathy, focal segmental glomerulosclerosis (FSGS) is the most common cause of nephrotic syndrome in European population. According to Columbia classification, there are five histological variants of FSGS defined on light microscopy (tip, cellular, perihilar, collapsing and not otherwise specified - NOS) and this classification has a prognostic significance. The aim is to compare features and outcomes of tip and cellular variant of primary FSGS. Method All patients with FSGS were identified by a retrospective review of the Registry of kidney biopsies at the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, from 2003 until 2020. Each kidney specimen was analyzed by light, immunofluorescent and electron microscopy and Columbia classification was applied by experienced nephropathologist. Patients with primary FSGS met following criteria: full nephrotic syndrome and diffuse podocyte foot process effacement in absence of secondary causes of FSGS. Laboratory findings were obtained for every patient at the time of biopsy and following outpatient visits. Complete remission was defined as proteinuria &lt; 0.3 g/day with normal kidney function and partial remission as proteinuria 0.3 - 3.5 g/day. Variables are expressed as median ± IQR (interquartile range) and frequencies. Statistical comparison between groups of patients with tip and cellular variant of primary FSGS and disease outcome analysis were done. Results Out of 200 patients with FSGS, 59 (29.5 %) had primary form of disease. Tip variant was the most common form of primary FSGS (22 patients, 37 %) followed by NOS (20, 34 %), cellular (13, 22 %), perihilar (2, 3.5 %) and collapsing (2, 3.5 %) variant. Demographic and clinical features with initial laboratory findings are shown in Table 1. There were no significant differences between two groups in all analyzed variables in Figure 1. All patients were treated by anti-RAAS agents and steroids. Median follow-up was 55 months (range 1 – 196 months), and followup data were unavailable for three patients. Figure 2 shows treatment regimens in both patient grouos with treatment outcomes. Remission rate was significantly higher in tip variant (90 % vs. 41 %, p = 0.002). There was no difference in relapse rate between the two groups (p = 0.717). Conclusion There were no significant differences in clinical features and laboratory findings at the time of clinical presentation between tip and cellular variant of primary FSGS. Patients with tip variant had significantly higher remission rate than patients with cellular variant.

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