**3. Cardiovascular disease in hemodyalysis**

### **3.1 Hyperphosphatemia and cardiovascular disease**

Cardiomyopathy and ischemic heart disease including acute myocardial infarctions, which are both common conditions in dialysis patients, likely play a role in the development of

Complications and Managements of Hyperphosphatemia in Dialysis 319

that dietary phosphate loading or elevation of serum phosphorus level may be a risk factor for cardiovascular disease in healthy persons as well as CKD patients (Takeda et al., 2006; Shuto et al., 2009). Di Marco et al. also reported that high phosphate loading increased ROS production via phosphate influx and induced apoptosis in endothelial cells (Di Marco et al., 2008). Association of serum phosphorus level and vascular dysfunction has been well investigated, because fasting serum phosphorus level could not increase in healthy persons, even if dietary phosphate was overloaded. However, postprandial phosphorus elevation was associated with %FMD in young healthy men (Shuto et al., 2009). Thus, dietary phosphate loading can cause endothelial dysfunction within a short time. Oxidative stress and decreased NO production in endothelial cells are possible mechanisms for the impaired

**PKC**⇑

**Atherosclerosis**

**Cardio Vascular Disease**

**Mönkeberg's sclerosis**

**NAD(P)H Oxidase**⇑ **eNOS** ⇓

**ROS**⇑ **NO**⇓

**Endothelial dysfunction**

**Osteopontin Cbfa-1 Calcification Osteocalcin**

**Induction of osteoblast differentiation**

Arterial disease observed in end-stage kidney disease patients is characterized by extensive intimal as well as medial calcification. Histological changes in coronary arteries from dialysis patients, compared with age matched controls, reveal a similar magnitude of atherosclerotic plaque burden and intimal thickness but markedly increased medial calcification (arteriolosclerosis) (Schwarz et al., 2000). Medial calcification has been shown to affect vascular elasticity and leads to increased arterial wall stiffness of large capacity, elastic-type arteries like the aorta and the common carotid artery, increased pulse pressure

endothelial function mediated by phosphate loading (Fig. 2).

inflammatory cytokine ⇑ adhesion molecules ⇑

**cell Vasorelaxation** ⇓

Fig. 2. Dual pathways for vascular dysfunction caused by hyperphosphatemia

**Smooth muscle cell**

**3.4 Arterial stiffness** 

**Phosphate**

**Endothelial**

sudden death. After percutaneous and surgical coronary revascularization, dialysis patients are still remaining at a high risk for sudden cardiac death (Furgeson, 2008). Hyperphosphatemia is a known factor contributing to the increased risk of cardiac death both in patients with end-stage renal disease and in those under renal replacement treatment with dialysis (Goodman et al., 2000). In patients with renal disease, in fact, the well-known relationship between hyperphosphataemia, secondary hyperparathyroidism, bone turnover and extra osseous calcifications has recently been followed by the recognition of a major role played by elevated serum phosphorus levels in the induction of vascular calcification, cardiac interstitial fibrosis and arterial thickening which highly increase the risk of cardiac death (Goodman et al., 2000; Block & Port, 2000; Amann et al., 2003; Goldsmith et al., 2004; Floege & Ketteler, 2004).
