scholarly journals Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Andreas Kronbichler ◽  
Johannes Leierer ◽  
Jun Oh ◽  
Björn Meijers ◽  
Jae Il Shin
Keyword(s):  
Clinical Practice ◽  
Focal Segmental Glomerulosclerosis ◽  
Transforming Growth Factor ◽  
Disease Onset ◽  
Significant Control ◽  
Segmental Glomerulosclerosis ◽  
History Of ◽  
Small Cohort ◽  
Stage Renal Disease ◽  
End Stage

Focal segmental glomerulosclerosis is a histological pattern on renal biopsy caused by diverse mechanisms. In its primary form, a circulatory factor is implicated in disease onset and recurrence. The natural history of primary FSGS is unpredictable, since some patients are unresponsive towards immunosuppressive measures. Immunologic changes, leading to a proinflammatory or profibrotic milieu, have been implicated in disease progression, namely, glomerular scarring, eventually leading to end-stage renal disease. Among these, interleukin-1ß, tumor-necrosis factor-α(TNF-α), and transforming growth factor-ß1 (TGF-ß1) have emerged as important factors. Translating these findings into clinical practice dampened the enthusiasm, since both TNF-αand TGF-ß1 blockade failed to achieve significant control of the disease. More recently, a role of the complement system has been demonstrated which in fact may be another attractive target in clinical practice. Rituximab, blocking CD20-bearing cells, demonstrated conflicting data regarding efficacy in FSGS. Finally, the T-cell costimulating molecule B7-1 (CD80) is implicated in development of proteinuria in general. Blockade of this target demonstrated significant benefits in a small cohort of resistant patients. Taken together, this review focuses on immunology of FSGS, attributable to either the disease or progression, and discusses novel therapeutic approaches aiming at targeting immunologic factors.

scholarly journals Update on Recurrent Focal Segmental Glomerulosclerosis in Kidney Transplantation

Nephron ◽  
2020 ◽  
pp. 1-6
Author(s):  
Jun Shoji ◽  
Akiko Mii ◽  
Mika Terasaki ◽  
Akira Shimizu
Keyword(s):  
Kidney Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Rapid Progression ◽  
Segmental Glomerulosclerosis ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
History Of ◽  
Stage Renal Disease ◽  
End Stage

<b><i>Background:</i></b> Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome characterized by nephrotic-range proteinuria with high incidence of progression to end-stage renal disease (ESRD). In primary FSGS, 40–60% of patients develop ESRD within 10–20 years. <b><i>Summary:</i></b> Recurrence of FSGS after kidney transplantation is frequent and is associated with poor allograft survival. The risk factors for recurrent FSGS include onset of FSGS during childhood, rapid progression of primary FSGS to ESRD, history of recurrent FSGS in previous allograft, and diffuse mesangial hypercellularity or collapsing variant of FSGS in the native kidney. The early histological findings of recurrent FSGS consist of unremarkable glomerular changes on light microscopy but significant podocyte effacement on electron microscopy; the loss of foot processes with eventual dropout of podocytes leads to the development of segmental lesions in the glomerulus. Experimental and clinical data suggest the existence of circulating permeability factors, such as soluble urokinase-type plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor-1 (CLCF-1), CD40 axis, and apolipoprotein A-Ib (ApoA-Ib), in the pathogenesis of recurrent FSGS. These biomarkers including circulating permeability factors may facilitate earlier diagnosis of FSGS posttransplant and may guide in the development of novel therapies that may be more effective and improve long-term outcomes in kidney transplantation. <b><i>Key Messages:</i></b> Several studies have suggested the possible circulating permeability factors, such as suPAR, CLCF-1, CD40 axis, and ApoA-Ib, in the pathogenesis and disease progression of FSGS and recurrent FSGS. Further studies should be performed to elucidate the true essential biomarker(s) associated with the onset and progression of FSGS as well as recurrent FSGS.

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.

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.

scholarly journals Circulating Permeability Factors in Primary Focal Segmental Glomerulosclerosis: A Review of Proposed Candidates

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Eva Königshausen ◽  
Lorenz Sellin
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Kidney Diseases ◽  
Individual Treatment ◽  
Pathogenic Role ◽  
Urokinase Plasminogen Activator Receptor ◽  
Permeability Factor ◽  
Segmental Glomerulosclerosis ◽  
Long Time ◽  
Stage Renal Disease ◽  
End Stage

Primary focal segmental glomerulosclerosis (FSGS) is a major cause of the nephrotic syndrome and often leads to end-stage renal disease. This review focuses on circulating permeability factors in primary FSGS that have been implicated in the pathogenesis for a long time, partly due to the potential recurrence in renal allografts within hours after transplantation. Recently, three molecules have been proposed as a potential permeability factor by different groups: the soluble urokinase plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor-1 (CLCF-1), and CD40 antibodies. Both CLCF-1 and CD40 antibodies have not been validated by independent research groups yet. Since the identification of suPAR, different studies have questioned the validity of suPAR as a biomarker to distinguish primary FSGS from other proteinuric kidney diseases as well as suPAR’s pathogenic role in podocyte damage. Researchers have suggested that cleaved molecules of suPAR have a pathogenic role in FSGS but further studies are needed to determine this role. In future studies, proposed standards for the research of the permeability factor should be carefully followed. The identification of the permeability factor in primary FSGS would be of great clinical relevance as it could influence potential individual treatment regimen.

scholarly journals Unsuccessful Treatment with Abatacept in Recurrent Focal Segmental Glomerulosclerosis after Kidney Transplantation

2017 ◽  
Vol 7 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Tilde Kristensen ◽  
Per Ivarsen ◽  
Johan Vestergaard Povlsen
Keyword(s):  
Renal Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Case Reports ◽  
Graft Function ◽  
Therapeutic Drug ◽  
Allograft Survival ◽  
Segmental Glomerulosclerosis ◽  
Unsuccessful Treatment ◽  
Stage Renal Disease ◽  
End Stage

Recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation occurs in up to 20–50% of FSGS patients and is associated with inferior allograft survival. Treatment of both primary FSGS as well as recurrent FSGS after transplantation with plasma exchange and immunosuppression is often unsuccessful and remains a major challenge as the disease still leads to end-stage renal disease and decreased graft survival. Previous case reports have described patients with recurrent FSGS who were successfully treated with a B7-1 inhibitor (abatacept) inducing partial or complete remission. The rational basis for believing in abatacept as a new therapeutic drug for the treatment of FSGS is the study by Yu et al. [N Engl J Med 2013;369: 2416–2423] showing B7-1 in immunostainings of the podocytes. The authors speculated that B7-1 immunostaining of renal biopsies might identify a subgroup of patients who would benefit from abatacept treatment. We present a case with recurrent FSGS after renal transplantation. The patient was unsuccessfully treated with B7-1 inhibitors. Although the patient was treated with abatacept 10 mg/kg body weight twice, the proteinuria and decreased graft function remained unchanged, and he never reached remission.

scholarly journals Successful treatment of collapsing focal segmental glomerulosclerosis in a patient

2020 ◽  
Vol 10 (4) ◽  
pp. e43-e43
Author(s):  
Luísa Helena Pereira ◽  
Ana Cabrita ◽  
Mário Góis ◽  
Helena Viana ◽  
Sandra Sampaio ◽  
...  
Keyword(s):  
Renal Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
End Stage Renal Disease ◽  
Oral Corticosteroid ◽  
Segmental Glomerulosclerosis ◽  
Number Of Patients ◽  
Collapsing Fsgs ◽  
Stage Renal Disease ◽  
End Stage ◽  
High Index Of Suspicion

Focal segmental glomerulosclerosis (FSGS) is a recognized cause of renal disease worldwide. The collapsing variant is distinct from the others, characterized clinically by a more severe nephrotic syndrome generally resistant to immunosuppressive therapy. It is known that a great number of patients progress to end-stage renal disease. Recognizing this lesion in biopsy is frequently challenging owing to the focal nature of the process which highlights the need for keeping a high index of suspicion for the diagnosis. We report and discuss a case of a non-HIV collapsing FSGS, followed by a complete (unexpected) renal recovery after an oral corticosteroid course.

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