Preface

Chronic kidney disease is an increasing health and economical problem in our world. Obesity and diabetes mellitus, the two most common cause of CKD, are becoming epidemic in our societies. Education on healthy lifestyle and diet is becoming more and more important for reducing the number of type 2 diabetics and patients with hypertension. Education of our patients is also crucial for successful maintenance therapy. There are, however, certain other factors leading to CKD, for instance the genetic predisposition in the case of polycystic kidney disease or type 1 diabetes, where education alone is not enough.

When the first angiotensin converting enzyme inhibitor, Captopril, was developed in 1975 it changed not only the treatment of hypertension, but of diabetic nephropathy and other chronic kidney diseases. In the past forty years we did not have such a breakthrough in the treatment of CKD. However, several valuable discoveries were made which greatly enhanced our understanding of the role of nitric oxide and mechanisms responsible for anemia and CKD-related bone diseases. Most certainly, dialysis techniques have developed greatly over the past seventy years and have become available for a wide range of people. Furthermore, advanced surgical procedures and tools were developed in the past years to resolve ureteral obstructions originating from stones or prostate hypertrophy. These modern techniques are discussed in our book along with currently accepted procedures for kidney cancers.

How can we further improve the treatment of CKD patients? Besides prevention, the most important aim would be to constantly look for, and try to understand the mechanistic details of disease development and progression. Perhaps no other disease is as complex and complicated as CKD since the symptoms result from the constant interaction of multiple organ systems as is the case with cardiorenal syndrome, CKDrelated anemia, and bone diseases. Because of the interdisciplinary nature of the disease, we need continuous communication between nephrologists, surgeons, and basic scientists, since only our joint approach can lay down the foundation of the next (bio)medical breakthrough. The chapters of our book introduce readers to this enthusiastic approach.

I would like to thank all of our contributors for their valuable time and expertise and for the high quality chapters which provide a greatly enjoyable reading experience. I

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also would like to thank my family and friends who supported me during the editing process: my Mom and Dad, Pal and Adam, and Carol of course. I dedicate this book to you.

> **Monika Göőz, MD PhD** Medical University of South Carolina Charleston, SC, USA

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you.

also would like to thank my family and friends who supported me during the editing process: my Mom and Dad, Pal and Adam, and Carol of course. I dedicate this book to

**Monika Göőz, MD PhD**

Charleston, SC,

USA

Medical University of South Carolina

**1**

*USA* 

Monika Göőz

**ADAM Proteases as Novel Therapeutic Targets** 

More than 20 million Americans suffer, and ultimately die, from chronic kidney disease (CKD). Based on data from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the yearly cost of dialysis treatment of patients with end stage renal disease (ESRD) is currently \$35 billion [1], and this number is predicted to rise as the US population ages and more people develop obesity, metabolic syndrome, and diabetes. CKD is associated with progressive renal fibrosis and inflammation, and currently there is no cure

The most common primary illnesses which result in end stage renal disease (ESRD) are diabetes (~37%), hypertension (~24%), glomerulonephritis (~15%), cystic kidney diseases (~4.7%) and urologic diseases (2.5%) [1]. There were 111,000 new ESRD patients diagnosed in 2007 and out of a total of ~500,000 ESRD patients 368,500 people received dialysis treatment in the same year. Dialysis patients have poor quality of life due to high hospitalization rate (458/1000 patients in 2008), high morbidity and mortality (~20%) [1]. Presently, kidney transplant is the only option for these patients to have a close to normal life. According to the US Renal Data System 2010 [1] however, out of the ~85,000 patients awaiting transplant about 18,000 will receive kidney since the amount of available organs

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used to attenuate the development of cardiovascular diseases and support renal function in CKD patients. However, novel therapeutic targets are desperately

Currently, there are about 2,000 clinical trials worldwide addressing some aspects and/or co-morbidities of CKD [2]. These include treatment of anemia, hypertension, secondary hyperparathyroidism, depression and inflammation among others. So far increasing frequency and quality of dialysis did not show advantages in survival rate [2]. Similarly, treatments targeting hypercholesterolemia [3] and hyperhomocysteinemia [4] or the usage

In recent years, we and others obtained exciting new data on the pathophysiological role of the disintegrin and metalloenzyme ADAMs in renal fibrosis and CKD. This chapter is dedicated to summerize these discoveries and discuss their significance and potential role in

did not increase significantly above this number for several years.

needed to effectively treat CKD and slow down disease progression.

of statins [5] failed to increase significantly the survival of ESRD patients.

the future treatment of patients with renal diseases.

**1. Introduction** 

for the disease.

**in Chronic Kidney Disease**

*Medical University of South Carolina, Charleston, SC* 
