The role of the immune system in idiopathic nephrotic syndrome

Abstract

Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia and usually responds well to steroids. However, relapses are frequent, which can require multi-drug therapy with deleterious long-term side effects. In the last decades, different hypotheses on molecular mechanisms underlying INS have been proposed and several lines of evidences strongly indicate a crucial role of the immune system in the pathogenesis of non-genetic INS. INS is traditionally considered a T-cell-mediated disorder triggered by a circulating factor, which causes the impairment of the glomerular filtration barrier and subsequent proteinuria. Additionally, the imbalance between Th17/Tregs as well as Th2/Th1 has been implicated in the pathomechanism of INS. Interestingly, B-cells have gained attention, since rituximab, an anti-CD20 antibody demonstrated a good therapeutic response in the treatment of INS. Finally, recent findings indicate that even podocytes can act as antigen-presenting cells under inflammatory stimuli and play a direct role in activating cellular pathways that cause proteinuria. Even though our knowledge on the underlying mechanisms of INS is still incomplete, it became clear that instead of a traditionally implicated cell subset or one particular molecule as a causative factor for INS, a multi-step control system including soluble factors, immune cells, and podocytes is necessary to prevent the occurrence of INS. This present review aims to provide an overview of the current knowledge on this topic, since advances in our understanding of the immunopathogenesis of INS may help drive new tailored therapeutic approaches forward.

Predictive Parameters of Steroid Dependency in Minimal Change Disease

“…6,7 Although, the pathogenesis of nephrotic syndrome remains uncertain, the role of the immune system and inflammation is reported in many studies. 3,4,13 Inflammatory mediators, such as neutrophils, lymphocytes, platelet, and platelet indices have been shown to be activated in NS. [14][15][16][17] The early prediction of patients with SDNS using these inflammatory parameters or other biochemical markers will therefore be useful to closely monitor these patients.…”

“…2 As the main treatment of MCD is immunosuppression with corticosteroids, immune system dysregulation strongly indicates a pathogenic role in disease development. 3,4 MCD generally responds well to corticosteroids, although 50-75% of patients, especially those aged <5 years, experience frequent disease relapses and half of the frequent relapsers eventually become steroid-dependent during steroid tapering or after discontinuation. [3][4][5][6] Patients with frequently relapsing NS (FRNS) or steroid-dependent NS (SDNS) are at a major risk of developing complications related to the prolonged use of steroids.…”

“…3,4 MCD generally responds well to corticosteroids, although 50-75% of patients, especially those aged <5 years, experience frequent disease relapses and half of the frequent relapsers eventually become steroid-dependent during steroid tapering or after discontinuation. [3][4][5][6] Patients with frequently relapsing NS (FRNS) or steroid-dependent NS (SDNS) are at a major risk of developing complications related to the prolonged use of steroids. 6,7 Thus, this study aimed to verify the predictive factors for NS attacks in pediatric patients with MCD.…”

Potential Molecular Mechanisms of Ephedra Herb in the Treatment of Nephrotic Syndrome Based on Network Pharmacology and Molecular Docking

“…Usually, NS responds well to steroids [ 6 ]. However, frequent recurrences are common, which will require multidrug therapy with long-term side effects [ 7 ]. Obviously, those problems not only increase the difficulty of treatment but also accelerate the development of end-stage renal disease (ESRD), which can be a catastrophic event for the patient, family, and even society [ 8 ].…”

Immunosuppression Exposure and Risk of Infection-Related Acute Care Events in Patients With Glomerular Disease: An Observational Cohort Study

“… 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 Putative risk factors for infection in patients with glomerular disease include exposure to immunosuppressive medications, systemic inflammation, altered immune cell function, and urinary loss of immunoglobulin and complement factors. 9 , 10 However, measuring the contribution to infection risk from individual factors is challenging because glomerular diseases can relapse and remit, in turn resulting in intermittent exposures to multiple immunosuppressive agents, alone and in combination, over the disease course. Previous estimates of infectious risk in patients with glomerular disease have been limited by small sample size, short follow-up duration, and restriction to baseline measurements of disease activity and immunosuppression exposure.…”