Advanced therapeutics in focal and segmental glomerulosclerosis

Abstract

Focal segmental glomerulosclerosis (FSGS) is a glomerulonephritis with podocyte injury. The renal prognosis of FSGS is relative poor. The overall remission rate of the FSGS patients with nephrotic syndrome to immunosuppressive treatments was reported as 47–66%, highlighting its therapeutic challenge—lacking in sufficient evidence‐based interventions. In first‐line treatment of nephrotic syndrome, daily oral prednisolone is a commonly used drug, whereas optimal treatment strategies, like indications and duration, remain controversial. Calcineurin inhibitor and cyclophosphamide are recommended in steroid‐dependent/steroid‐resistant patients. However, the high unmet need in effective immunosuppressive treatments calls for the development of new therapy methods. Rituximab, a monoclonal antibody targeting CD20 B‐cells, could increase the complete or partial remission rate, and decrease the relapse rate based on several previous studies on FSGS. In addition, the using of rituximab could potentially help the FSGS patients to stop the concomitant therapy include steroid and immunosuppressive agents. Other treatment options like adalimumab or abatacept also showed potential therapeutic effect, but still required larger Randomized Controlled Trial study to determine its efficiency and safety. Besides, expanding understanding of the genetic basis of FSGS is necessary to investigate new therapeutic agents. With the unsatisfied patients’ outcome under the current treatments, innovation should be encouraged on the treatment strategy based on Kidney Disease: Improving Global Outcomes guideline and international collaborations are required for the potential novel immunosuppressive or immunomodulatory therapies.

Consolidation Treatment and Long-Term Prognosis of Rituximab in Minimal Change Disease and Focal Segmental Glomerular Sclerosis

“…15,16 Potential side effects may include infection, diabetes, osteoporosis, osteonecrosis of the femoral head, gonadal inhibition, myelosuppression, and obesity. 1 In light of these factors, RTX looks to be an alternative as we did not observe negative effects in our patients after its administration. This study aims to critically assess our past success through retrospective analysis.…”

“…Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) account for 60% of nephrotic syndrome (NS) - one of the main causes of glomerulosclerosis in China. 1 RTX which is a CD20 lymphocyte monoclonal antibody that causes B lymphocyte depletion 2 is widely used in treatments of autoimmune diseases and immune-mediated kidney diseases such as lupus erythematosus and vasculitis. 3 , 4 Depletion of B cells that interact with T cells in MCD, and participate in the production of circulating factors in FSGS, is achieved through antiproteinuric effects of RTX through methods of direct, indirect, and cytotoxic effects.…”

“… 15 , 16 Potential side effects may include infection, diabetes, osteoporosis, osteonecrosis of the femoral head, gonadal inhibition, myelosuppression, and obesity. 1 …”

A rare renal involvement in a patient with axial Spondyloarthritis: don’t miss focal segmental glomerulosclerosis and hyalinosis

“…This later has been used since 2006 for the treatment of SpA (18). It has also been used in refractory cases of FSGS since 2014, it reduces proteinuria and protect kidney function from degradation, it has also been reported as an alternative in cases of resistance or allergy to rituximab in FSGS (19,20).…”

Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: a prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial

“…Treatment of FSGS depends on the aetiology and severity, with immunosuppression usually offered to patients with primary disease and supportive therapies including reninangiotensin-aldosterone system (RAAS) blockade for those with the adaptive form [5][6][7].…”