Rituximab in Adult Minimal Change Disease and Focal Segmental Glomerulosclerosis

Kronbichler, Andreas; Bruchfeld, Annette

doi:10.1159/000368590

Cited by 17 publications

(9 citation statements)

References 22 publications

(36 reference statements)

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“…Case reports and small case series have shown potential for rituximab in steroid-sensitive FSGS, but it appears largely ineffective in steroid resistant disease [76, 77]. …”

Section: Major Therapeutic Advancesmentioning

confidence: 99%

Recent Treatment Advances and New Trials in Adult Nephrotic Syndrome

Königshausen

Sellin

2017

BioMed Research International

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The etiology of nephrotic syndrome is complex and ranges from primary glomerulonephritis to secondary forms. Patients with nephrotic syndrome often need immunosuppressive treatment with its side effects and may progress to end stage renal disease. This review focuses on recent advances in the treatment of primary causes of nephrotic syndrome (idiopathic membranous nephropathy (iMN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS)) since the publication of the KDIGO guidelines in 2012. Current treatment recommendations are mostly based on randomized controlled trials (RCTs) in children, small RCTs, or case series in adults. Recently, only a few new RCTs have been published, such as the Gemritux trial evaluating rituximab treatment versus supportive antiproteinuric and antihypertensive therapy in iMN. Many RCTs are ongoing for iMN, MCD, and FSGS that will provide further information on the effectiveness of different treatment options for the causative disease. In addition to reviewing recent clinical studies, we provide insight into potential new targets for the treatment of nephrotic syndrome from recent basic science publications.

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“…Case reports and small case series have shown potential for rituximab in steroid-sensitive FSGS, but it appears largely ineffective in steroid resistant disease [76, 77]. …”

Section: Major Therapeutic Advancesmentioning

confidence: 99%

Recent Treatment Advances and New Trials in Adult Nephrotic Syndrome

Königshausen

Sellin

2017

BioMed Research International

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“…B-cell biology, however, has attained more attention lately, since treatment with rituximab, a monoclonal antibody directed against CD20 bearing cells, has shown good therapeutic responses in the treatment of both childhood and adulthood MCNS 7 71 72 73) . Children with frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome had a significantly longer relapse-free period in the rituximab group compared to the control group 7 8 73) .…”

Section: B-cell Abnormality and Efficacy Of Rituximabmentioning

confidence: 99%

Pathogenesis of minimal change nephrotic syndrome: an immunological concept

et al. 2016

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Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia. Minimal change nephrotic syndrome (MCNS) is the most common form of INS in children. The pathogenesis of MCNS still remains unclear, however, several hypotheses have been recently proposed. For several decades, MCNS has been considered a T-cell disorder, which causes the impairment of the glomerular filtration barrier with the release of different circulating factors. Increased levels of several cytokines are also suggested. Recently, a "two-hit" theory was proposed that included the induction of CD80 (B7-1) and regulatory T-cell (Treg) dysfunction, with or without impaired autoregulatory functions of the podocyte. In contrast to the well-established involvement of T cells, the role of B cells has not been clearly identified. However, B-cell biology has recently gained more attention, because rituximab (a monoclonal antibody directed against CD20-bearing cells) demonstrated a very good therapeutic response in the treatment of childhood and adult MCNS. Here, we discuss recent insights into the pathogenesis of MCNS in children.

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“…Though the accurate mechanism by which rituximab, a monoclonal antibody against CD20, induces remission in MCD patients remains uncertain, recent observations of the effect of rituximab on complicated refractory SSNS 27 – 29 suggests a pathophysiological role for B cells in MCD 30 , 31 ( Figure 1 ). B cell depletion by rituximab resets and suppresses B cell and T cell interactions and keeps the Th17/Treg balance normal, which may lead to sustainable remission 32 , 33 .…”

Section: Rituximab and B Cell Dysfunctionmentioning

confidence: 99%

Cell biology and genetics of minimal change disease

Saleem

Kobayashi

2016

F1000Res

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Minimal change disease (MCD) is an important cause of nephrotic syndrome and is characterized by massive proteinuria and hypoalbuminemia, resulting in edema and hypercholesterolemia. The podocyte plays a key role in filtration and its disruption results in a dramatic loss of function leading to proteinuria. Immunologic disturbance has been suggested in the pathogenesis of MCD. Because of its clinical features, such as recurrent relapse/remission course, steroid response in most patients, and rare familial cases, a genetic defect has been thought to be less likely in MCD. Recent progress in whole-exome sequencing reveals pathogenic mutations in familial cases in steroid-sensitive nephrotic syndrome (SSNS) and sheds light on possible mechanisms and key molecules in podocytes in MCD. On the other hand, in the majority of cases, the existence of circulating permeability factors has been implicated along with T lymphocyte dysfunction. Observations of benefit with rituximab added B cell involvement to the disease. Animal models are unsatisfactory, and the humanized mouse may be a good model that well reflects MCD pathophysiology to investigate suggested “T cell dysfunction” directly related to podocytes in vivo. Several candidate circulating factors and their effects on podocytes have been proposed but are still not sufficient to explain whole mechanisms and clinical features in MCD. Another circulating factor disease is focal segmental glomerulosclerosis (FSGS), and it is not clear if this is a distinct entity, or on the same spectrum, implicating the same circulating factor(s). These patients are mostly steroid resistant and often have a rapid relapse after transplantation. In clinical practice, predicting relapse or disease activity and response to steroids is important and is an area where novel biomarkers can be developed based on our growing knowledge of podocyte signaling pathways. In this review, we discuss recent findings in genetics and podocyte biology in MCD.

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Rituximab in Adult Minimal Change Disease and Focal Segmental Glomerulosclerosis

Cited by 17 publications

References 22 publications

Recent Treatment Advances and New Trials in Adult Nephrotic Syndrome

Recent Treatment Advances and New Trials in Adult Nephrotic Syndrome

Pathogenesis of minimal change nephrotic syndrome: an immunological concept

Cell biology and genetics of minimal change disease

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