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Primary forms of minimal change disease and focal segmental glomerulosclerosis are rare podocytopathies and clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of the initial immunosuppressive treatment in these two entities. Especially among adults with minimal change disease or focal segmental glomerulosclerosis, relapses, steroid dependence or resistance are common and necessitate re-initiation of steroids and other immunosuppressants. Effective steroid-sparing therapies and introduction of less toxic immunosuppressive agents are urgently needed to reduce undesirable side effects, in particular for patients whose disease course is complex. Rituximab, a B cell depleting monoclonal antibody, is increasingly used off-label in these circumstances, despite a low level of evidence for adult patients. Hence, critical questions concerning drug-safety, long-term efficacy and the optimal regimen for rituximab-treatment remain unanswered. Evidence in the form of large, multicenter studies and randomized controlled trials are urgently needed to overcome these limitations., Competing Interests: Declaration of Competing Interest VA reports grants from ADDMEDICA, outside the submitted work; AB reports consulting fees from Chemocentryx, from Merck/MSD and from Astra Zeneca, outside the submitted work; MB reports lecture fees from Boehringer Ingelheim, from Bristol-Myers Squibb, from Novartis, travel support from Hexal, lecture fees and travel support from Vifor Fresenius and lecture fee from Servier, outside the submitted work; CKC reports grants from GlaxoSmithKline, grants and consultancy fees from Retrophin, outside the submitted work; SF reports lecture fees from VIFOR Pharma, outside the submitted work; CK reports being funded by National Institute for Health Research (NIHR) as academic clinical fellow (ACF), during the conduct of the study. All the other authors declared no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Rituximab (RTX), a chimeric, monoclonal anti-CD20 antibody, is increasingly used in immune-mediated renal diseases. While licensed in the induction treatment of ANCA-associated vasculitis, it represents one of the most commonly prescribed off-label drugs. Much of the information regarding its safety has been drawn from experience in hematology and rheumatology. Ample evidence illustrates the safety of RTX, however, rare but serious adverse events have emerged that include progressive multifocal leucoencephalopathy and hepatitis B reactivation. Moderate to severe hypogammaglobulinemia and late-onset neutropenia following RTX therapy confer an increased infectious risk and factors predicting these side effects (i.e. a genetic basis) need to be identified. Nephrologists initiating RTX need to bear in mind that long-term risks and optimal dosing for many renal indications remain unclear. Special considerations must be given when RTX is used in women of childbearing age. We summarize practical aspects concerning the use of RTX. This review will provide nephrologists with information to guide their use of RTX alerting them to safety risks and the need for patient counselling., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Refractory lupus nephritis indicates an inadequate response to lupus nephritis therapy. It implies persisting or worsening disease activity despite therapy, but the definition is complicated by the parameters of response, proteinuria and renal function, that do not discriminate clearly between activity and irreversible damage. Understanding the causes of refractory disease and developing treatment strategies is important because these patients are more likely to develop poor outcomes, especially end stage renal disease. This review explores current concepts and definitions of refractory disease and summarises treatment approaches that have been used in observational cohort studies and case series. We highlight the importance of optimising adherence to the prescribed immunosuppressive and supportive measures and avoidance of diagnostic delay. Treatment options include higher dose glucocorticoid, switching between cyclophosphamide and mycophenolate acid derivates, or addition of rituximab, the latter potentially in combination with belimumab. Less evidence supports extracorporeal treatment (plasma exchange or immunoadsorption), calcineurin inhibitors (cyclosporine A or tacrolimus), intravenous immunoglobulin and stem cell transplantation. Improvements in understanding what refractory disease is and how definitions can be integrated into treatment pathways has the potential to enhance lupus nephritis outcomes. [ABSTRACT FROM AUTHOR]