[Frontiers in Bioscience E4, 1058-1070, January 1, 2012]
Obesity-related glomerulopathy and podocyte injury: a mini review Marcello Camici1, Fabio Galetta1, Nader Abraham2, Angelo Carpi2

1Department of Internal Medicine, University of Pisa, Italy, 2Department of Physiology and Pharmacology, University of Toledo, USA, 2Department of Reproduction and Ageing, University of Pisa, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Mechanisms of podocyte injury or dysfunction 3.1 .Angiotensin II
3.2. Aldosterone
3.3. Plasminogen activator inhibitor-1 (PAI-1)
3.4. Lipid metabolism
3.5. Adiponectin
3.5.1. General aspects
3.5.2. Adiponectin and podocytes
3.6. Macrophages and proinflammatory cytokines
3.7. Inflammation and oxidative stress
4. Pharmacologic targeting of podocyte injury in obesity-related glomerulopathy
4.1. AT2 receptor blockers
4.2. Adipokine complement C19 TNF-related protein-1 blocker
4.3. Selective PAI-1 inhibitor
4.4. Farnesoid x receptor activation
4.5. Increase of circulating adiponectin
4.6.Selective antiinflammatory drugs
4.7. More potent antioxidans (Heme oxigenase, NOX4 inhibitors)
5. Conclusion
6. References

1. ABSTRACT

Obesity-related glomerulopathy (ORG) is morphologically defined as focal segmental glomerulosclerosis and glomerulomegaly. Podocyte hypertrophy and reduced density are related to proteinuria which in a portion of patients is in the nephrotic range and evolvs towards renal failure. This article reviews the pathogenetic mechanisms of podocyte injury or dysfunction and lists new possible antiproteinuric strategies based on pharmaceutical targeting of the reported pathogenetic mechanisms. The pathogenetic mechnisms discussed include: renin angiotensin system, plasminogen activation inhibitor-1 (PAI-1), lipid metabolism, adiponectin, macrophages and proinflammatory cytokines, oxidative stress. The proposed antiproteinuric strategies include: AT2 receptor blockers; adipokine complement C19 TNF-related protein-1 blocker; selective PAI-1 inhibitor; farnesoid x receptor activation; increase of circulating adiponectin; selective antiinflammatory drugs; more potent antioxidants (Heme oxigenase, NOX4 inhibitors). However, because ORG is a rare disease, the need for a long term pharmaceutical approach in obese proteinuric patients should be carefully evaluated and limited to the cases with progressive loss of renal function.