A A Elmarakby, D M Pollock, and J D Imig, Medical College of Georgia, Augusta, GA, USA © 2007 Elsevier Ltd. All Rights Reserved.

6.25.1 Introduction 575

6.25.2 Causes of Renal Dysfunction 576 Hypertension 576 Obesity 576 Diabetes 578 Type 1 diabetes 578 Type 2 diabetes 578 Prognosis of Renal Dysfunction 579 Mechanisms of Renal Dysfunction 579 Enhanced sympathetic activity 579 Endothelial dysfunction 580 Nitric oxide 580 Oxidative stress 581 Role of inflammation cytokines 581 20-Hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids 582 Endothelin in hypertension 583 Renin-Angiotensin system 583

6.25.3 Experimental Disease Models 584

6.25.4 Clinical Trial Issues 585

6.25.5 Management of Renal Dysfunction 585 Diuretics 585 ß-Adrenoceptor Blockers 587 Calcium Channel Blockers 588 Modulating the Renin-Angiotensin System 588 Angiotensin Receptor Blockers 588 ACE Inhibitors and Aldosterone Receptor Antagonism 590

6.25.6 Unmet Medical Need 590

6.25.7 Emerging Approaches to Treat Renal Dysfunction 590 Antioxidants 590 Endothelin Receptor Antagonists 591 Inhibitors of the Synthesis of 20-Hydroxyeicosatetraenoic Acid 591 Epoxyeicosatrienoic Acid Mimetics and Soluble Epoxide Hydrolase

Inhibitors 592

6.25.8 Summary 592 References 592

Renal dysfunction is defined as failure of the kidney to adequately retain essential nutrients and clear out toxic substances from the blood. It has become an increasing epidemic problem in the world, especially in the elderly population. An estimated 10-20 million Americans have impaired renal function and they have a high risk for

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