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Idiopathic nephrotic syndrome (INS) is characterized by three different entities, namely minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) and membranous nephropathy (MN). While there is an increasing understanding of primary MN with the discovery of antibodies directed against phospholipase A2 receptor (PLA2R Ab) and thrombospondin type 1 domain-containing 7A, circulatory factors causative of inducing MCD and FSGS remain in part elusive. Extracorporeal treatment forms (mostly plasma exchange) have been reserved for patients with either a disease course refractory to commonly prescribed immunosuppressive drugs or to patients with recurrence after kidney transplantation. There is a paucity of data supporting the use of immunoadsorption (IAS) in the management of MCD and MN and evidence to perform LDL-apheresis in the former is limited to reports from Japan. Treatment with IAS in primary FSGS has shown mixed responses, possibly biased by including treatment-resistant cases in the absence of genetic testing. In those with recurrence of the disease following kidney transplantation, IAS has shown high remission rates with an acceptable safety profile. There is a need to compare IAS to plasma exchange (PLEX) in this indication and due to a higher amount of plasma processed during one session, IAS may have advantages over PLEX. Removal of PLA2R Ab by IAS is currently being tested in a phase II clinical trial. More clinical trials in a prospective and randomized fashion need to be designed to prove the concept that IAS may be a treatment option for INS. While PLEX is still the leading extracorporeal treatment form in these indications, this review aims to highlight the efficacy and safety of IAS in the management of INS. [ABSTRACT FROM AUTHOR]

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]

Extracorporeal treatments have been used since the 1970s in the management of systemic lupus erythematosus (SLE). A randomised controlled trial comparing the efficacy of standard of care (SOC) combined with plasma exchange against SOC alone in patients with lupus nephritis revealed no difference in terms of renal outcome. Subsequently, initial expectations have been dampened and further experience with plasma exchange is mainly limited to observational studies and single case reports. Beneficial effects have been reported in patients with refractory disease course or in pregnancy with prior complications due to SLE and antiphospholipid syndrome. A more specific form of extracorporeal treatment, immunoadsorption (IAS), has emerged as a valuable option in the treatment of SLE. In line with the plasma exchange experience, IAS seems to have beneficial effects in patients with refractory disease, contraindications to standard immunosuppression or during pregnancy. The mechanism IAS relates to autoantibody removal but for plasma exchange removal of activated complement components, coagulation factors, cytokines and microparticles may also be relevant. Both treatment forms have good safety profiles although reactions to blood product replacement in plasma exchange and procedure related complications such as bleeding or catheter-related infections have occurred. There is a need to more clearly define the clinical utility of plasma exchange and IAS in refractory lupus and APS subgroups. [ABSTRACT FROM AUTHOR]