**2. CKD and its impact on outcomes after CABG**

Chronic kidney disease is defined as derangement in renal function for a period of at least six months. It is broadly divided into five stages based on creatinine clearance or glomerular filtration rate (GFR) obtained from either Cockcroft-Gault or modification of diet in renal disease (MDRD) equations [3,4]:

© 2013 Chaudhry et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Cockcroft-Gault equation: Creatinine Clearance (ml/min) = [([140 − age] × weight [kg])/72 × serum creatinine (mg/dl)] (× 0.85 for women),

mation which is a key pathogenic mechanism in atherosclerosis; vitamin D also has an antiproliferative effect on myocardial cell hypertrophy and proliferation and prevents remodeling which underlies the pathogenesis of congestive heart failure and vitamin D acts as an inhibito‐ ry endocrine regulator for the renin-angiotensin system, which triggers the cascade of hyper‐ tension and decompensated heart failure[8]. Thus, with low 1,25 hydroxy cholecalciferol

Impact of Renal Dysfunction and Peripheral Arterial Disease on Post-Operative Outcomes ...

http://dx.doi.org/10.5772/54417

439

We will discuss the outcomes of patients with CKD with the two modes of revascularization namely percutaneous and then, surgical. Additionally, we will take into account the impact of various comorbidities such as diabetes, dyslipidemias with respect to lipoprotein levels as

Although long-term mortality may improve with surgical revascularization in dialysis pa‐ tients with coronary artery disease, perioperative mortality continues to remain higher among patients with end-stage renal disease (ESRD) requiring CABG. Various studies have compared the outcomes of percutaneous coronary intervention (PCI) versus CABG and showed that mor‐ tality is not different [9-11]. However, these studies were from the 1990s and percutaneous techniques have been refined since then with improved outcomes. Newer studies are required

In hemodialysis dependent patients (CKD stage 5), clinical outcomes of PCI are especially poor. Before the advent of coronary stents 20 years ago, when percutaneous revasculariza‐ tion was performed with balloon angioplasty alone, it was found that patients with ESRD experience a higher rate of coronary restenosis and recurrent angina, when compared to pa‐ tients without ESRD [12]. In another case control study of twenty patients with ESRD and 20 age and sex matched controls without renal disease, it was shown that the rate of restenosis was 60% in ESRD patients, as compared to 35% in patients without renal disease. Restenosis was found to be dependent on size of vessel dilated and there was increased prothrombotic

Many patients with ESRD experience silent ischemia. The possible mechanism being uremic

In a prospective study of 5327 patients undergoing percutaneous coronary intervention (PCI) with a follow up of over five years, rate of death or myocardial infarction at one year was 1.5% in CKD patients with creatinine clearance >70 ml/min, 3.6% in patients with creati‐ nine clearance between 50-70 ml/min, 7.8% between 30 and 49 ml/min and 18.1% with crea‐ tinine clearance less than 30ml/min. This study showed a progressive increase in adverse outcomes with worsening renal function. CKD was a strong predictor of adverse cardiovas‐

Even though conflicting studies exist, a large study has shown that although there is in‐ creased risk of mortality in patients with ESRD undergoing CABG when compared to pa‐

polyneuropathy and therefore, may not experience typical ischemic symptoms.

levels, this effect is pronounced causing even further increase in cardiovascular risk.

well as the role of oxidative stress in this patient population.

**2.2. Outcomes with percutaneous coronary intervention**

risk secondary to increased fibrinogen concentrations [13].

cular events including death and MI [14].

**2.3. CABG in patients with renal dysfunction**

to compare outcomes of percutaneous versus surgical revascularization.

MDRD equation: GFR (mL/min/1.73 m2 ) = 175 × (serum creatinine)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American) (conventional units)

Creatinine clearance or glomerular filtration rate (GFR) represents renal function. Declining values represent a decline in renal function. Stage 1 refers to glomerular filtration rate (GFR) >90 ml/min and is generally asymptomatic. GFR between 60-90 ml/min is stage 2 CKD. Stage 3 is GFR between 30 and 60 ml/min and is further subdivided into Stage 3A (GFR 45-60 ml/min) and Stage 3B (GFR 30-45 ml/min). Stage 4 is defined by GFR between 15-30 ml/min while GFR <15 ml/min signifies Stage 5 and is considered an indication for renal re‐ placement therapy i.e. dialysis. The most common etiological factors for CKD include diabe‐ tes mellitus and hypertension resulting in diabetic nephropathy and hypertensive nephrosclerosis, respectively.

The presence of CKD is considered a major independent predictor for development of coro‐ nary artery disease (CAD). An analysis from the atherosclerosis risk in communities (ARIC) study, Manjunath et al demonstrated that in 15,350 subjects with a mean follow up of over 6 years, there was a significant increase in acute coronary syndrome events in patients with stage 3 and 4 CKD (14.2%) compared with 5.5% in patients with stage 1 CKD (HR 1.38 (1.02, 1.87). Additionally, with every 10 ml/min/1.73 m2 decline in GFR, there was a progressive increase in the incidence of cardiac events [5].

#### **2.1. Proposed pathogenic mechanisms**

Many factors contribute in the mechanisms associated in the renal contribution to increased risk of cardiovascular events. We briefly discuss a few here: Impaired renal function is asso‐ ciated with reduced erythropoietin synthesis and consequent anemia, which has been asso‐ ciated with cardiovascular disease [6]. Reduced 1, 25 (OH) vitamin D synthesis is associated with increased parathyroid hormone levels and higher prevalence of vascular calcification and arteriosclerosis [7].

Abnormal calcium phosphate metabolism is a consequence of renal dysfunction and it has a strong association with increased adverse cardiovascular events. Hyperphosphatemia and hy‐ percalcemia are distinctly independent risk factors leading to a greater occurrence of cardio‐ vascular events in patients with CKD and additionally, are also associated with poor surgical outcomes in patients undergoing CABG. Increased calcium-phosphate product greater than 55 and hyperphosphatemia escalates the development of secondary hyperparathyroidism which has been linked to increased osteoclastic activity and enhanced calcium-phosphate precipita‐ tion in the vasculature. There is also increase in the number of protein receptors in vessel cell membrane which increases deposition of calcium. In patients with CKD, vitamin D deficiency is also present even in the early stages. Vitamin D levels have a pivotal role in calcium-phos‐ phorus homeostasis, regulation of parathyroid hormone (PTH), and bone metabolism and turnover. Three plausible mechanisms have been suggested in the protective effects of vitamin D against cardiovascular disease mortality are that vitamin D can inhibit various foci of inflam‐ mation which is a key pathogenic mechanism in atherosclerosis; vitamin D also has an antiproliferative effect on myocardial cell hypertrophy and proliferation and prevents remodeling which underlies the pathogenesis of congestive heart failure and vitamin D acts as an inhibito‐ ry endocrine regulator for the renin-angiotensin system, which triggers the cascade of hyper‐ tension and decompensated heart failure[8]. Thus, with low 1,25 hydroxy cholecalciferol levels, this effect is pronounced causing even further increase in cardiovascular risk.

We will discuss the outcomes of patients with CKD with the two modes of revascularization namely percutaneous and then, surgical. Additionally, we will take into account the impact of various comorbidities such as diabetes, dyslipidemias with respect to lipoprotein levels as well as the role of oxidative stress in this patient population.

Although long-term mortality may improve with surgical revascularization in dialysis pa‐ tients with coronary artery disease, perioperative mortality continues to remain higher among patients with end-stage renal disease (ESRD) requiring CABG. Various studies have compared the outcomes of percutaneous coronary intervention (PCI) versus CABG and showed that mor‐ tality is not different [9-11]. However, these studies were from the 1990s and percutaneous techniques have been refined since then with improved outcomes. Newer studies are required to compare outcomes of percutaneous versus surgical revascularization.

### **2.2. Outcomes with percutaneous coronary intervention**

Cockcroft-Gault equation: Creatinine Clearance (ml/min) = [([140 − age] × weight [kg])/72 ×

Creatinine clearance or glomerular filtration rate (GFR) represents renal function. Declining values represent a decline in renal function. Stage 1 refers to glomerular filtration rate (GFR) >90 ml/min and is generally asymptomatic. GFR between 60-90 ml/min is stage 2 CKD. Stage 3 is GFR between 30 and 60 ml/min and is further subdivided into Stage 3A (GFR 45-60 ml/min) and Stage 3B (GFR 30-45 ml/min). Stage 4 is defined by GFR between 15-30 ml/min while GFR <15 ml/min signifies Stage 5 and is considered an indication for renal re‐ placement therapy i.e. dialysis. The most common etiological factors for CKD include diabe‐ tes mellitus and hypertension resulting in diabetic nephropathy and hypertensive

The presence of CKD is considered a major independent predictor for development of coro‐ nary artery disease (CAD). An analysis from the atherosclerosis risk in communities (ARIC) study, Manjunath et al demonstrated that in 15,350 subjects with a mean follow up of over 6 years, there was a significant increase in acute coronary syndrome events in patients with stage 3 and 4 CKD (14.2%) compared with 5.5% in patients with stage 1 CKD (HR 1.38 (1.02,

Many factors contribute in the mechanisms associated in the renal contribution to increased risk of cardiovascular events. We briefly discuss a few here: Impaired renal function is asso‐ ciated with reduced erythropoietin synthesis and consequent anemia, which has been asso‐ ciated with cardiovascular disease [6]. Reduced 1, 25 (OH) vitamin D synthesis is associated with increased parathyroid hormone levels and higher prevalence of vascular calcification

Abnormal calcium phosphate metabolism is a consequence of renal dysfunction and it has a strong association with increased adverse cardiovascular events. Hyperphosphatemia and hy‐ percalcemia are distinctly independent risk factors leading to a greater occurrence of cardio‐ vascular events in patients with CKD and additionally, are also associated with poor surgical outcomes in patients undergoing CABG. Increased calcium-phosphate product greater than 55 and hyperphosphatemia escalates the development of secondary hyperparathyroidism which has been linked to increased osteoclastic activity and enhanced calcium-phosphate precipita‐ tion in the vasculature. There is also increase in the number of protein receptors in vessel cell membrane which increases deposition of calcium. In patients with CKD, vitamin D deficiency is also present even in the early stages. Vitamin D levels have a pivotal role in calcium-phos‐ phorus homeostasis, regulation of parathyroid hormone (PTH), and bone metabolism and turnover. Three plausible mechanisms have been suggested in the protective effects of vitamin D against cardiovascular disease mortality are that vitamin D can inhibit various foci of inflam‐

) = 175 × (serum creatinine)-1.154 × (Age)-0.203 × (0.742 if

decline in GFR, there was a progressive

serum creatinine (mg/dl)] (× 0.85 for women),

female) × (1.212 if African American) (conventional units)

1.87). Additionally, with every 10 ml/min/1.73 m2

increase in the incidence of cardiac events [5].

**2.1. Proposed pathogenic mechanisms**

and arteriosclerosis [7].

MDRD equation: GFR (mL/min/1.73 m2

438 Artery Bypass

nephrosclerosis, respectively.

In hemodialysis dependent patients (CKD stage 5), clinical outcomes of PCI are especially poor. Before the advent of coronary stents 20 years ago, when percutaneous revasculariza‐ tion was performed with balloon angioplasty alone, it was found that patients with ESRD experience a higher rate of coronary restenosis and recurrent angina, when compared to pa‐ tients without ESRD [12]. In another case control study of twenty patients with ESRD and 20 age and sex matched controls without renal disease, it was shown that the rate of restenosis was 60% in ESRD patients, as compared to 35% in patients without renal disease. Restenosis was found to be dependent on size of vessel dilated and there was increased prothrombotic risk secondary to increased fibrinogen concentrations [13].

Many patients with ESRD experience silent ischemia. The possible mechanism being uremic polyneuropathy and therefore, may not experience typical ischemic symptoms.

In a prospective study of 5327 patients undergoing percutaneous coronary intervention (PCI) with a follow up of over five years, rate of death or myocardial infarction at one year was 1.5% in CKD patients with creatinine clearance >70 ml/min, 3.6% in patients with creati‐ nine clearance between 50-70 ml/min, 7.8% between 30 and 49 ml/min and 18.1% with crea‐ tinine clearance less than 30ml/min. This study showed a progressive increase in adverse outcomes with worsening renal function. CKD was a strong predictor of adverse cardiovas‐ cular events including death and MI [14].
