Immunopathogenesis of idiopathic nephrotic syndrome with relapse

Abstract

Idiopathic change nephrotic syndrome (INS), the most frequent glomerular disease in children and young adults, is characterized by heavy proteinuria and a relapsing remitting course. Although the mechanisms underlying the pathophysiology of proteinuria remain unclear, clinical and experimental observations suggest that lymphocyte and podocyte disturbances are two sides of the disease. The current hypothesis suggests that immune cells release a putative factor, which alters podocyte function resulting in nephrotic proteinuria. Besides T-cell abnormalities, recent evidence of B-cell depletion efficacy in sustained remissions added a new challenge in understanding the immunological mechanisms of INS. In this review, we discuss recent insights related to podocyte disorders occurring in INS and their relevance in human diseases.

Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors for response, long-term outcomes and tolerance

“…Other cases were considered as a failure of RTX. B-cell recovery was defined by a CD19+ lymphocyte count of > 1 mm 3 . A relapse that occurred within 2 months after withdrawal of other IS drugs and in <3 months after RTX was also considered a failure of RTX.…”

“…The efficacy of drugs that target cellular immunity, with steroids as the first choice, suggests that MCNS could be caused by a systemic T-cell function disorder. This hypothesis has been reinforced by the identification of common regulatory pathways between podocytes and T cells, involving the c-mip protein [3][4][5]. A number of alternative immunosuppressive drugs (ISs), including alkylating agents, calcineurin inhibitors (CNIs) and mycophenolate mofetil (MMF), have been tested in steroid-dependent or steroid-resistant patients with conflicting results and potential serious side effects.…”

“…A number of alternative immunosuppressive drugs (ISs), including alkylating agents, calcineurin inhibitors (CNIs) and mycophenolate mofetil (MMF), have been tested in steroid-dependent or steroid-resistant patients with conflicting results and potential serious side effects. However, subsequent studies have shown that ISs may be effective as non-specific anti-proteinuric agents and that a defect of proximal signalling and cytoskeleton remodelling in podocyte may be the main molecular mechanism leading to MCNS [3,6]. Therefore, new drugs with safer profiles need to be tested for the treatment of this disease.…”

Idiopathic Adult Nephrotic Syndrome: A Clinicopathological Study and Response to Steroid in a Sub-Saharan African Country

“…It is a clinical translation of a podocyte injury and represents 25% to 30% of glomerulonephritis in adults [1]. It constitutes the most recurrent revelation of about 50% of chronic kidney diseases observed as well in the United States, in Europe or in Africa [2].…”

Ten-year advances in immunopathology of glomerulonephritis: translated into patients’ care or lost in translation?

“…Although substantial progresses have been made in understanding the immunopathology of minimal change disease (MCD) [11], IgA nephropathy [12], ANCA-related vasculitis [13], and lupus nephritis [14], they have not yet translated into major diagnostic and treatment improvements. The nature of the putative circulating permeability factor(s) in MCD and FSGS is still elusive despite some clues provided by works on podocyte-secreted angiopoietin-like 4 [15] and, more controversial, suPAR, the soluble urokinase-type plasminogen activator receptor [16].…”