As part of the glomerular filtration membrane, podocyte is terminally differentiated, structurally unique, and highly specialized in maintaining kidney function. Proteinuria caused by podocyte injury (foot process effacement) is the clinical symptom of various kidney diseases (CKD), including nephrotic syndrome. Podocyte autophagy has become a powerful therapeutic strategy target in ameliorating podocyte injury. Autophagy is known to be associated significantly with sirtuin-1, proteinuria, and podocyte injury. Various key findings in podocyte autophagy were reported in the past ten years, such as the role of endoplasmic reticulum (ER) stress in podocyte autophagy impairment, podocyte autophagy-related gene, essential roles of the signaling pathways: Mammalian Target of Rapamycin (mTOR)/ Phosphoinositide 3-kinase (PI3k)/ serine/threonine kinase 1 (Akt) in podocyte autophagy. These significant factors caused podocyte injury associated with autophagy impairment. Sirtuin-1 was reported to have a vital key role in mTOR signaling, 5'AMP-activated protein kinase (AMPK) regulation, autophagy activation, and various critical pathways associated with podocyte's function and health; it has potential value to podocyte injury pathogenesis investigation. From these findings, podocyte autophagy has become an attractive therapeutic strategy to ameliorate podocyte injury, and this review will provide an in-depth review on therapeutic targets he podocyte autophagy.
Minimal change disease (MCD) is the most common cause of idiopathic nephrotic syndrome in children, and it is well known for its multifactorial causes which are the manifestation of the disease. Proteinuria is an early consequence of podocyte injury and a typical sign of kidney disease. Steroid-sensitive patients react well with glucocorticoids, but there is a high chance of multiple relapses. CD80, also known as B7-1, is generally expressed on antigen-presenting cells (APCs) in steroid-sensitive MCD patients. Various glomerular disease models associated with proteinuria demonstrated that the detection of CD80 with the increase of urinary CD80 was strongly associated closely with frequent-relapse MCD patients. The role of CD80 in MCD became controversial because one contradicts finding. This review covers the treatment alternatives for MCD with the insight of CD80 as a potential therapeutic target. The promising effectiveness of CD20 (rituximab) antibody and CD80 inhibitor (abatacept) encourages further investigation of CD80 as a therapeutic target in frequent-relapse MCD patients. Therapeutic-based antibody towards CD80 (galiximab) had never been investigated in MCD or any kidney-related disease; hence, the role of CD80 is still undetermined. A new therapeutic approach towards MCD is essential to provide broader effective treatment options besides the general immunosuppressive agents with gruesome adverse effects.