Therapeutic targets in focal and segmental... : Current Opinion in Nephrology and Hypertension (original) (raw)

Renal pathophysiology: Edited by Orson W. Moe and Susan Quaggin

Therapeutic targets in focal and segmental glomerulosclerosis

Lavin, Peter Ja,b; Gbadegesin, Rasheeda,b; Damodaran, Tirupapuliyur Va,b; Winn, Michelle Pa,b

aDepartment of Medicine, USA

bCenter for Human Genetics, Duke University Medical Center, Durham, North Carolina, USA

Correspondence to Michelle P. Winn, Center for Human Genetics, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA Tel: +1 919 660 0038; e-mail: [email protected]

Current Opinion in Nephrology and Hypertension 17(4):p 386-392, July 2008. | DOI: 10.1097/MNH.0b013e32830464f4

Abstract

Purpose of review

Focal and segmental glomerulosclerosis occurs due to a defect in the glomerular filtration barrier. This review highlights contributions from the past year that have enhanced our understanding of the pathophysiology of focal and segmental glomerulosclerosis with emphasis on discoveries which may lead to the identification of therapeutic targets.

Recent findings

Slit diaphragm proteins have become increasingly important in signal transduction and in mediating downstream events. Actin polymerization occurs after the podocin–nephrin–Neph-1 complex is phosphorylated by Src kinase and Fyn. Recent studies of angiotensin receptor antagonists, corticosteroids and erythropoietin unravel new mechanisms that ameliorate proteinuria by targeting the cell cycle within the podocyte. The discovery that an N-acetylmannosamine kinase (MNK) mutant mouse has glomerulopathy is suggestive that human sialylation pathways may represent therapeutic targets. Proteinuria before podocyte effacement demonstrated in laminin-β2 null mice highlights the importance of the glomerular basement membrane. Interferon-β reduced proteinuria in three models of kidney injury, showing greatest effect on glomerular endothelial cells in vitro.

Summary

Basic research has illuminated mechanisms by which classic therapies have antiproteinuric effects directly on the podocyte. As knowledge expands with improved molecular techniques, understanding signaling pathways in health and proteinuric states should lead to potential therapeutic targets in focal and segmental glomerulosclerosis.