**3.9 Erythropoietin and correction of anemia**

Anemia is common in both HF and CKD, and the term "cardiorenal-anemia syndrome" refers to the coexistence of anemia and the CRS. EPO is widely used in the CKD population to correct anemia to a moderate degree. Studies in this population have shown improved parameters of cardiac performance with EPO therapy, including reduction of left ventricular hypertrophy and dilatation, improved left ventricular ejection fraction, and increased cardiac output (Linde et al., 1996; Low et al., 1989; Low-Friedrich et al., 1991). Studies of EPO and iron administration to patients with HF with or without CKD have shown inconsistent results, but some studies have demonstrated modest improvements in symptoms and functional capacity as well as renal function, ejection fraction, and left ventricular dimensions (Bolger et al., 2006; Palazzuoli et al., 2006; Silverberg et al., 2000; Toblli et al., 2007). The FAIR-HF (Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency) study demonstrated improved symptoms and functional capacity in patients with HF and iron deficiency, even in the absence of overt anemia, treated with intravenous iron as compared to placebo (Anker et al., 2009). The ongoing IRON-HF (Iron Supplementation in Heart Failure Patients With Anemia) and RED-HF (Reduction of Events With Darbepoetin Alfa in Heart Failure ) studies will likely further clarify the role of iron and EPO therapies in patients with HF and provide additional insights into the management of the CRS.

#### **4. Conclusions and future directions**

The Cardiorenal Syndrome is a pathophysiologic state involving complex feedback processes between the failing heart and failing kidneys, and is associated with a

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**9**

*Taiwan* 

**Atherosclerotic Renovascular Disease** 

Atherosclerotic renovascular disease (ARVD), also known as atherosclerotic renal artery stenosis is increasingly recognized to be a cause of chronic renal failure. According to a recent administrative data regarding general population of the elderly greater than 65 years of age in the United States, the prevalence and incidence rates of ARVD were estimated 0.5% and 3.7 per each 1000 person-years respectively (Kalra et al., 2005). In addition, some epidemiological researches demonstrated that the prevalence among those with end-stage renal disease beginning renal replacement therapy was estimated from 5% to 22% (Rimmer & Gennari, 1993; Mailloux et al., 1994; Appel et al., 1995; van Ampting et al., 2003). Of note, ARVD is not only responsible to impaired kidney function but also reflects a status of patients at risk for systemic cardiovascular diseases (Kalra et al., 2005). It has been well known that a variety of risk factors for atherosclerosis share common pathway underlying atherosclerotic renal artery stenosis, coronary artery disease, and peripheral vascular disease. On the contrary, significant high-grade bilateral or isolated renal artery stenosis may cause renovascular hypertension estimating over 50% of ARVD populations by activation of renin-angiotensin-aldosterone system and lipoxygenase pathway that further deteriorate the kidney function (Romero 1997). A previous report uncovered that ARVD was estimated from 1% to 6% in patients with hypertension (Simon et al., 1972). In this regard, a vicious cycle will be established in the progression of renal arterial atherosclerosis, which is characterized by refractory hypertension, acute cardiac events (ie, heart failure, cardiogenic pulmonary edema or acute coronary syndrome), and hence leads to acute or chronic renal failure due to hypertensive or ischemic nephropathy (Buller et al., 2004). Therefore, an early alert of patients at risk for ARVD is critical in slowing down the rate of kidney function loss and providing treatment for underlying cardiovascular disease as well. In this chapter, we will fuel the readers with the classic knowledge in this field and propose

the latest evidence-based medicine to manage patients with this disease.

Atherosclerosis is affected by the traditional risk factors including hypertension, smoking, hyperlipidemia, diabetes mellitus and family history of premature coronary artery disease systemically. Regionally, blood flow disturbances near arterial branches, bifurcations and curvatures result in complex spatiotemporal shear stresses that are associated with

**2. The pathogenesis of atherosclerosis** 

**1. Introduction**

Gen-Min Lin, Chih-Lu Han, Chung-Chi Yang

and Cheng-Chung Cheng *National Defense Medical Center* 

