Role of the glucocorticoid receptor in glomerular disease

Abstract

Glucocorticoids are potent anti-inflammatory agents that are commonly used in the treatment of various glomerular diseases. Data from in vitro and in vivo studies, in both animals and humans, convincingly demonstrate that glucocorticoids have many beneficial direct effects on glomeruli, including podocytes, suggesting that, in theory, systemic administration is not necessary to achieve therapeutic benefit. Indeed, it is increasingly recognized that systemic steroids often have an unfavorable risk-to-benefit ratio. As we move into an age of personalized medicine, strategies to develop targeted steroid delivery systems and individualized risk assessment algorithms are desirable in clinicians’ efforts to “first, do no harm.”

Effectiveness of gene-expression connectivity analysis for evaluating treatment effects of frequent medicines on kidney in IgA nephropathy

“…However, the oral or intravenous use of glucocorticoids had severe side effects and gradually increased with the focus on locally targeted drugs. In vivo and in vitro studies have shown that glucocorticoids have direct renal effects, which might protect podocytes from injuries by regulating multiple podocyte-speci c targets, including nephrin, Rac1, RhoA, and actinin, while conditional knockout of the glucocorticoid receptor (GR) gene of podocytes makes mice more vulnerable to lipopolysaccharide (LPS) [23][24][25]. Colombo et al developed a nanoparticle for targeting and enriching dexamethasone into glomeruli to repair podocytes [26].…”

Recent Advances in Cell Membrane Coated-Nanoparticles as Drug Delivery Systems for Tackling Urological Diseases

“…The dose-dependent nature of glucocorticoids can produce serious side effects (osteoporosis, concentric obesity, infection, etc.) in clinical applications of treatment for renal inflammation [ 145 , 146 ]; therefore, Tang et al used macrophage-derived MVs delivered with dexamethasone (DEX) to treat renal inflammation and demonstrated superior ability to suppress renal inflammation compared to DEX treatment alone, without obvious adverse effects. LFA-1 and VLA-4 present on MV-DEX were responsible for their homing to the inflamed kidney.…”

Role of Endothelial Glucocorticoid Receptor in the Pathogenesis of Kidney Diseases

“…Novel studies unravel a more complex relationship. For example, GCs protect podocytes through stabilisation of the slit diaphragm and cytoskeleton and preserve podocyte differentiation after injury [44]. Moreover, mice with GR knockout in podocytes are more vulnerable to kidney injury by various factors and show worse proteinuria and podocyte foot process effacement.…”