Pathogenesis of minimal change nephrotic syndrome: an immunological concept

Abstract

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.

Clinical characteristics and risk factors of severe infections in hospitalized adult patients with primary nephrotic syndrome

“…Patients with NS have defective cell-mediated immunity. 7 – 9 Additionally, steroid or immunosuppressive therapy in patients with NS causes immunological dysfunction, which leads to increased susceptibility to infections. 10 , 11 Episodes of NS complicated by major infections usually require admission for aggressive treatment and affect patients’ outcomes.…”

Flu B or not Flu B: An atypical case of minimal change disease triggered by Influenza B presenting with multi-organ dysfunction

“…15 Other contributors possibly include increased IL-13 production from T cells, podocyte derived CD80 or angiopoietin-like-4 protein up regulation, or circulatory factors such as vascular permeability factor, and hemopexin. 16 B cells also likely play a role, with Rituximab found as being non-inferior to steroid treatment for steroid-dependent nephrotic syndrome in children. 17 Influenza A, as well as other viruses including cytomegalovirus (CMV), Epstein Barr virus (EBV), human immunodeficiency virus (HIV), parvovirus, dengue virus, and others can present with hepatic injury.…”

The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?

“…These observations emphasize the heterogeneity of histopathologic features of injury from ICIs, as well as the immune activation seen in patients with ICIs-AKI. A further mechanism leading to podocyte foot process impairment, as observed for minimal-change disease and focal segmental glomerulosclerosis, could be the persistent, chronic release of inflammatory cytokines by T cells associated to ICIs-induced abrogation of CTLA-4 signaling ( 61 ).…”