Pathophysiology and treatment of focal segmental glomerulosclerosis: the role of animal models

Abstract

Focal segmental glomerulosclerosis (FSGS) is a kidney disease with progressive glomerular scarring and a clinical presentation of nephrotic syndrome. FSGS is a common primary glomerular disorder that causes renal dysfunction which progresses slowly over time to end-stage renal disease. Most cases of FSGS are idiopathic Although kidney transplantation is a potentially curative treatment, 40% of patients have recurrence of FSGS after transplantation. In this review a brief summary of the pathogenesis causing FSGS in humans is given, and a variety of animal models used to study FSGS is discussed. These animal models include the reduction of renal mass by resecting 5/6 of the kidney, reduction of renal mass due to systemic diseases such as hypertension, hyperlipidemia or SLE, drug-induced FSGS using adriamycin, puromycin or streptozotocin, virus-induced FSGS, genetically-induced FSGS such as via Mpv-17 inactivation and α-actinin 4 and podocin knockouts, and a model for circulating permeability factors. In addition, an animal model that spontaneously develops FSGS is discussed. To date, there is no exact understanding of the pathogenesis of idiopathic FSGS, and there is no definite curative treatment. One requirement facilitating FSGS research is an animal model that resembles human FSGS. Most animal models induce secondary forms of FSGS in an acute manner. The ideal animal model for primary FSGS, however, should mimic the human primary form in that it develops spontaneously and has a slow chronic progression. Such models are currently not available. We conclude that there is a need for a better animal model to investigate the pathogenesis and potential treatment options of FSGS.

Recent advances of animal model of focal segmental glomerulosclerosis

“…Despite the differences in disease characteristic between humans and animals, animal models have been an essential component of medical research for centuries. One of the most important differences is that many animal models reflect secondary FSGS, whereas primary FSGS is much more common disease form in human [6]. However, the final result of the pathology remains the same between the two disease forms, justifying the use of animal models in understanding the underlying mechanisms behind FSGS.…”

Translational value of animal models of kidney failure

“…The main characteristics are podocyte loss, glomerular fibrosis and proteinuria. Animal models have been recently reviewed (de Mik et al, 2013). In this section only models of primary focal segmental glomerulosclerosis due to specific podocyte injury will be discussed.…”

Epigallocatechin-3-Gallate Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis via Suppression of Oxidant Stress and Apoptosis by Targeting Hypoxia-Inducible Factor-1α/ Angiopoietin-Like 4 Pathway

“…So, FSGS seriously endangers human health. FSGS usually characterized by podocyte injury and heavy proteinuria [1] and multiple causes are related to FSGS, including circulating permeability factors, genetic defects, toxins and obesity [4]. But, importantly, it also has been demonstrated that overproduction of reactive oxygen species (ROS) and cell apoptosis are associated with the development of FSGS [5,6].…”