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Open Access Highly Accessed Review

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

Sylvana ML de Mik1, Martin J Hoogduijn3, Ron W de Bruin1 and Frank JMF Dor12*

Author Affiliations

1 Laboratory of experimental surgery, Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

2 Department of surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

3 Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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BMC Nephrology 2013, 14:74  doi:10.1186/1471-2369-14-74

Published: 1 April 2013

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.

Keywords:
Focal segmental glomerulosclerosis; Animal model; Remnant kidney; Adriamycin; Puromycin aminonucleoside-induced nephrosis; hiv; Mpv-17; α-actinin 4