Abstract
Idiopathic nephrotic syndrome (INS) is an important primary glomerular disease characterized by severe proteinuria. Evidence supports a role for T cell dysfunction in the pathogenesis of INS. Glucocorticoids are the primary therapy for INS; however, steroid-resistant NS (SRNS) patients are at a higher risk of drug-induced side effects and harbor poor prognosis. Although the exact mechanism of the resistance is unknown, the imbalances of T helper subtype 1 (Th1), Th2, and regulatory T cells (Tregs) and their cytokines may be involved in the pathogenesis of glucocorticoid responsiveness. Up to now, no confirmed biomarkers have been able to predict SRNS; however, a panel of cytokines may predict responsiveness and identify SRNS patients. Thus, the introduction of distinctive cytokines as novel biomarkers of SRNS enables both preventions of drug-related toxicity and earlier switch to more effective therapies. This review highlights the impacts of T cell population imbalances and their downstream cytokines on response to glucocorticoid responsiveness state in INS.
Highlights
Idiopathic nephrotic syndrome (INS) is a clinical definition, described by extreme proteinuria due to podocyte injury and foot process effacement
T cell deviation towards the T helper subtype 2 (Th2) population in NS patients might be linked to the overproduction of IL-13. These findings propose that T helper subtype 1 (Th1)-dominant patients might develop glucocorticoid-resistance, while increased IL-13 and Th2 phenotypes are in favor of a satisfactory outcome, and glucocorticoid responsiveness
In children with new-onset NS, glucocorticoid therapy decreases the levels of plasma cytokines secreted by CD8+, CD4+ TH1, and
Summary
Idiopathic nephrotic syndrome (INS) is a clinical definition, described by extreme proteinuria due to podocyte injury and foot process effacement. The production of cytokines stimulates the formation of acute-phase proteins such as haptoglobin, haemopexin, or C-reactive protein (CRP), suPAR (soluble urokinase-type plasminogen activator receptor), α-1 antitrypsin, and fibrinogen in the liver. Different studies have reported the plausible connection between cytokine production and proteinuria in INS [4, 5]. Glucocorticoids are the standard initial pharmacological regimen in INS, which block the production of cytokines in both immune and nonimmune cells effectively and result in Mediators of Inflammation remissions in approximately 85-90% of pediatric cases. Glucocorticoids represent a key index of outcomes, and drug-resistant patients pose a challenge to clinicians. The response to glucocorticoids has been considered as the key variable in long-term outcomes of FSGS and MCD patients [11]. The potential effects of glucocorticoids highlight the possible role of cytokines in determining the drug response. SRNS patients without podocyte genetic defects may respond to other immunosuppressive agents, such as cyclosporine, tacrolimus, and mycophenolate
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