scholarly journals Treatment Strategies of Adult Primary Focal Segmental Glomerulosclerosis: A Systematic Review Focusing on the Last Two Decades

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Arno Beer ◽  
Gert Mayer ◽  
Andreas Kronbichler
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Remission Rate ◽  
Alkylating Agents ◽  
Treatment Options ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Calcineurin Inhibitors ◽  
Segmental Glomerulosclerosis ◽  
Steroid Dependent ◽  
Stage Renal Disease

Adult primary focal segmental glomerulosclerosis (FSGS) remains a therapeutic challenge for the treating physician. With the advent of novel immunosuppressive measures, our arsenal of therapeutic options increased considerably. The aim of this review was to summarize reports published over the last two decades which reported on treatment outcome. Most reports included patients with a steroid-resistant (SR) disease course, yet the cohort with the highest unmet need, since persistent nephrotic range proteinuria is associated with a poor renal prognosis and portends a high risk of developing end-stage renal disease. While in first-line treatment, steroid treatment remains the recommended standard with an overall remission rate of 50% and higher, optimal treatment strategies for steroid-dependent/multirelapsing (SD/MR) and SR patients have to be defined. In both entities, calcineurin inhibitors showed good efficacy, while mycophenolate mofetil was less effective in SR cases compared to those with SD/MR. The same was true for rituximab, a monoclonal antibody targeting B-cells. In resistant cases, addition of extracorporeal treatment options or treatment with alkylating agents may be considered. To shape the future for treatment of FSGS, international collaborations to conduct larger clinical trials are needed to identify potential novel efficacious immunosuppressive or immunomodulatory therapies.

scholarly journals P0372RITUXIMAB IN IDIOPATHIC FOCAL SEGMENTAL GLOMERULOSCLEROSIS OF THE ADULT: A MULTICENTRE RETROSPECTIVE SURVEY OF 31 PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Martina Tedesco ◽  
Isabella Pisani ◽  
Marco Allinovi ◽  
Giovanni Casazza ◽  
Lucia Del Vecchio ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Focal Segmental Glomerulosclerosis ◽  
Immunosuppressive Treatment ◽  
Case Series ◽  
Post Transplantation ◽  
Steroid Resistant ◽  
Segmental Glomerulosclerosis ◽  
Steroid Dependent ◽  
Stage Renal Disease

Abstract Background and Aims Idiopathic Focal Segmental Glomerulosclerosis (FSGS) is a rare glomerulonephritis often complicated by a chronic relapsing course frequently characterized by dependency or resistance to immunosuppressive treatment. Moreover, about half of the patients with active disease would develop end-stage renal disease within 10 years from the diagnosis, highlighting the need of novel therapeutic approaches. Rituximab (RTX), a chimeric monoclonal antibody against CD20, showed promising results in pediatric steroid-dependent/frequently relapsing FSGS and in post-transplantation recurrence. However, evidence about its role in the FSGS of the adult is still lacking with small case series suggesting conflicting results. In this study we assess the efficacy of RTX in the largest cohort of adults with FSGS currently available in literature. Methods Adults with biopsy proven idiopathic FSGS treated with RTX were retrospectively identified among several Italian nephrology units. Response to RTX was evaluated at 3, 6, 12 months and, when available, during the long-term follow-up. A positive response (POR) was defined as: (1) proteinuria <3.5 g/die with a decrease >50% compared to baseline, (2) stable renal function (3) decreased or stable dose of glucocorticoids and other immunosuppressants. Severe Adverse Events (SAEs) have been recorded. Results 31 patients have been identified: 18 steroid-dependent, 11 steroid-resistant, and 2 patients with major contraindication to steroid therapy. RTX has been administered at a median of 87 months (IQR 54–96) from the diagnoses using heterogeneous schedules of administration. Overall, the POR rate at 6 months was 52% (steroid-dependent=69%; steroid-resistant=22%). At univariate analyses, POR to RTX at 6 months was associated to the steroid-dependent status (p=0.0347) and a proteinuria at RTX <5 g/die (p=0.0173); a trend towards better response was observed in patients with IgG at RTX <500 mg/dl (p=0.0774). Over the first year of follow-up, the proteinuria and serum albumin significantly improved (respectively, p=0.0021 and p=0.0277 at 12 months), while serum creatinine remained stable (figure). Among treated patients, the median dose of prednisone decreased from 15 mg/die (IQR 12.5–25) at baseline to 10 mg/die (IQR 5–15) at 12 months, while the proportion of patients free from glucocorticoids respectively increased from 42% to 54%. Six patients have been retreated within a year since the first RTX: of these only the 2 patients who have experienced a POR to the first administration obtained a further POR after retreatment. After the 12th month, 11 patients have been followed for a median time of 17 months (IQR 15–33.5): of the 5/11 with a POR at the 12th month, 2/5 maintained a POR without needing further immunosuppression, 2/5 maintained a POR with a pre-emptive RTX based maintenance treatment, 1/5 experienced a relapse successfully managed with RTX needing then a pre-emptive RTX based maintenance therapy able to allow a persistent POR. Overall, 9 SAEs have been recorded with requirement of hospital admission for clinical deterioration being the most frequent. Conclusion RTX may be an option in the FSGS of the adult, especially in the steroid-dependent patients and the ones with less severe nephrotic syndrome. In the responders, a RTX based maintenance therapy may be required.

scholarly journals Recent Advances in Treatments of Primary Focal Segmental Glomerulosclerosis in Children

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Kyoung Hee Han ◽  
Seong Heon Kim
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Calcineurin Inhibitors ◽  
Steroid Treatment ◽  
Renal Survival ◽  
Steroid Resistant ◽  
Segmental Glomerulosclerosis ◽  
Risk Of Progression ◽  
Traditional Therapies ◽  
Stage Renal Disease ◽  
End Stage

Focal segmental glomerulosclerosis (FSGS) is a nephrotic syndrome. Up to around 80% of cases of primary FSGS are resistant to steroid treatment. A large proportion of patients with steroid-resistant FSGS progress to end-stage renal disease. The purpose of treatment is to obtain a complete remission of proteinuria, a necessary step that precedes improved renal survival and reduces the risk of progression to chronic kidney disease. When this is not possible, the secondary goal is a partial remission of proteinuria. Reduction or remission of proteinuria is the most important factor predictive of renal survival. We will review the current updated strategies for treatment of primary FSGS in children, including traditional therapies consisting of corticosteroids and calcineurin inhibitors and novel therapies such as rituximab, abatacept, adalimumab, and fresolimumab.

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.

scholarly journals A Case of Nephrotic Syndrome, Showing Evidence of Response to Saquinavir

2015 ◽  
Vol 2015 ◽  
pp. 1-3 ◽  
Author(s):  
Giles Walters ◽  
Faisal A. Choudhury ◽  
Budhima Nanayakkara
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Idiopathic Nephrotic Syndrome ◽  
Treatment Options ◽  
Immunosuppressive Drugs ◽  
Significant Side Effect ◽  
Steroid Resistant ◽  
Segmental Glomerulosclerosis ◽  
Steroid Dependent ◽  
Frequent Relapses

The treatment of primary nephrotic syndrome such as minimal change nephropathy, membranous nephropathy, and focal segmental glomerulosclerosis nephropathy remains challenging. Whilst most cases of idiopathic nephrotic syndrome respond to steroid therapy and experience a limited number of relapses prior to complete remission, some cases suffer from frequent relapses and become steroid dependent or are primarily steroid resistant. Treatment options are limited to immunosuppressive drugs with significant side effect profiles. New modalities targeting novel pathways in the pathogenesis of nephrotic syndrome are actively sought. Here we report the case of a patient with steroid dependent focal segmental glomerulosclerosis (FSGS) nephrotic syndrome with a favourable response to a novel proteasome inhibitor saquinavir.

scholarly journals Focal Segmental Glomerulosclerosis

1999 ◽  
Vol 10 (9) ◽  
pp. 1900-1907
Author(s):  
MELVIN M. SCHWARTZ ◽  
JONI EVANS ◽  
RAY BAIN ◽  
STEPHEN M. KORBET
Keyword(s):  
Serum Creatinine ◽  
Focal Segmental Glomerulosclerosis ◽  
End Stage Renal Disease ◽  
Poor Response ◽  
Steroid Treatment ◽  
Response To Treatment ◽  
Therapeutic Trial ◽  
Segmental Glomerulosclerosis ◽  
Stage Renal Disease ◽  
End Stage

Abstract. The cellular lesion (CELL), seen in some patients with primary focal segmental glomerulosclerosis (FSGS), comprises proliferation, hypertrophy, and pathologic changes in the cells overlying the glomerular scar. The prognosis of the cellular lesion was retrospectively studied in 100 patients with FSGS (43 had FSGS-CELL and 57 had FSGS without the cellular lesion (classic segmental scar [CS]). Patients with the FSGS-CELL lesion were more often black and severely proteinuric and developed more end-stage renal disease (ESRD). Nephrotic patients with FSGS-CELL (n = 39) were more proteinuric at presentation than patients with FSGS-CS (n = 36). ESRD developed more frequently in patients with the FSGS-CELL (17 of 39, 44% versus 5 of 36, 14%, P = 0.005), and patients with extensive FSGS-CELL (≥ 20% glomeruli) were mainly black (94%), severely nephrotic (67%, >10 g/d), and had a poor response to treatment (23% remission). In nephrotic patients, initial serum creatinine, interstitial expansion ≥20%, and CELL independently predicted ESRD. However, the rates of remission in treated nephrotic patients with FSGS-CELL and FSGS-CS were the same (9 of 17, 53% versus 17 of 39, 52%), and patients in both groups who achieved a remission had a 5-yr survival of 100%. Steroid treatment was the only variable that predicted remission. Patients with the FSGS-CELL have an increased prevalence of ESRD, but the improved prognosis associated with remission is so significant that a therapeutic trial is warranted in all nephrotic FSGS patients, regardless of the presence of the cellular lesion.

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 < 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.

Comparison of treatment options in adults with frequently relapsing or steroid-dependent minimal change disease

2020 ◽  
Author(s):  
Cihan Heybeli ◽  
Stephen B Erickson ◽  
Fernando C Fervenza ◽  
Marie C Hogan ◽  
Ladan Zand ◽  
...  
Keyword(s):  
Median Time ◽  
Minimal Change Disease ◽  
Treatment Options ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Minimal Change ◽  
Line Treatment ◽  
Second Line ◽  
Steroid Dependent ◽  
Time To Relapse

Abstract Background Studies comparing all treatment options for frequently-relapsing/steroid-dependent (FR/SD) minimal change disease (MCD) in adults are lacking. Methods Medical records of 76 adults with FR/SD MCD who were treated with corticosteroids as the first-line therapy were reviewed. Treatment options were compared for the time to relapse, change of therapy and progression (relapse on full-dose treatment). Results Second-line treatments included rituximab (RTX; n = 13), mycophenolate mofetil (MMF; n = 12), calcineurin inhibitors (CNI; n = 26) and cyclophosphamide (CTX; n = 16). During the second-line treatments, 48 (71.6%) patients relapsed at median 17 (range 2–100)  months. The majority of relapses occurred during dose tapering or off drug. Twenty of 65 (30.8%) changed therapy after the first relapse. The median time to relapse after the second line was 66 versus 28 months in RTX versus non-RTX groups (P = 0.170). The median time to change of treatment was 66 and 44 months, respectively (P = 0.060). Last-line treatment options included RTX (n = 8), MMF (n = 4), CNI (n = 3) and CTX (n = 2). Seven (41.2%) patients had a relapse during the last-line treatment at median 39 (range 5–112)  months. The median time to relapse was 48 versus 34 months in the RTX versus non-RTX groups (P = 0.727). One patient in the RTX group died presumably of heart failure. No major adverse event was observed. During the median follow-up of 81 (range 9–355)  months, no patients developed end-stage renal disease. Conclusions Relapse is frequent in MCD in adults. Patients treated with RTX may be less likely to require a change of therapy and more likely to come off immunosuppressive drugs.

scholarly journals Systemic lupus erythematosus and diffuse alveolar hemorrhage, etiology and novel treatment strategies

Lupus ◽  
2020 ◽  
Vol 29 (4) ◽  
pp. 355-363 ◽  
Author(s):  
N K Al-Adhoubi ◽  
J Bystrom
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Factor Vii ◽  
Systemic Lupus ◽  
Mesenchymal Stem Cell Therapy

Diffuse alveolar hemorrhage is a severe respiratory complication of systemic lupus erythematosus. The illness develops over hours to a few days and is the systemic lupus erythematosus-associated syndrome with highest mortality. Although no specific symptoms have been identified, a number of features are associated with diffuse alveolar hemorrhage, with a drop in blood hemoglobin the most prominent. Dyspnea, blood-stained sputum, diffuse infiltrates identified by chest imaging, elevated single breath-diffusing capacity for monoxide, thrombocytopenia and C3 hypocomplementemia are other commonly reported signs of diffuse alveolar hemorrhage. The etiology is not completely understood but many patients develop diffuse alveolar hemorrhage concomitant with lupus nephritis, suggesting immune complex-driven pathology. Biopsy studies have identified both cases with capillaritis and a bland non-inflammatory phenotype. An animal model of diffuse alveolar hemorrhage has indicated requirement of B lymphocytes and complement receptor-mediated apoptotic body phagocytosis by monocytes as part of the pathogenesis. This review will discuss considerations when diagnosing the condition and available therapies. Infections and other causes of hemorrhage have to be excluded as these require different treatment strategies. Methylprednisolone and cyclophosphamide remain the most commonly used therapies. Plasmapheresis and rituximab are other beneficial treatment options. A few studies have also considered intrapulmonary Factor VII therapy, extracorporeal membrane oxygenation and mesenchymal stem cell therapy. There is an unmet need of better definition of diffuse alveolar hemorrhages etiology and pathology for development of improved treatment strategies.

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