**2.5. Impact of mode of dialysis on outcomes after CABG**

The mode of dialysis is equally important in influencing CABG outcomes, namely perito‐ neal (PD) and hemo-dialysis (HD). Peritoneal dialysis has been associated with worse out‐ comes when compared with hemodialysis [21,22]. Following CABG, diaphragmatic splinting, atelectasis and hypoxemia can occur after early post-operative initiation of PD. In a retrospective analysis of 105 patients, among whom 40 were on PD, and 65 on HD and all patients had been on dialysis for at least 2 months prior to CABG, it was demonstrated that the incidence of post- operative dialysate leak and peritonitis was 10% and 12.5% respective‐ ly in patients on PD. On the other hand, incidence of arterio-venous access thrombosis was 4.6% in patients on HD. Besides older age, PD was an independent risk factor of high opera‐ tive mortality (adjusted OR for in hospital mortality in PD patients was 22.58). Actual causes of mortality included sepsis, cardiac arrest, pneumonia and gastrointestinal bleed. Chief in‐ fective organisms in septic patients were Staphylococcus aureus (coagulase negative), Pseu‐ domonas aeruginosa, and Enterococcus faecalis [21]. Risk of peritonitis is higher if gastroepiploic artery is harvested for CABG as it requires diaphragmatic incision [22].

#### **2.6. Impact of comorbidities in patients with CKD undergoing CABG**

Diabetes and hypertension are the most common causes of CKD and they are also the major risk factors for coronary artery disease, therefore, the incidence of CAD is higher in these patients.

### *2.6.1. Diabetes*

tients without significant renal disease, it still portends a better outcome in terms of mortality when compared to percutaneous revascularization in this patient population [15].

It has been shown that the lower the GFR, the worse the mortality after CABG. In a study of 2067 patients, it was found that estimated GFR was a powerful and independent predictor of mortality in multivariate analysis. Estimated average GFR in patients who died was

In a database review of 483,914 CABG patients over a three year period, it was shown that the post-operative mortality rates for stage 2, stage 3, and stage 4 CKD patients were 1.8%, 4.3% and 9.3 % respectively. Also, there was a higher incidence of stroke, need for re-opera‐ tion, sternal infection, prolonged mechanical ventilation greater than 48 hours and a hospital stay of longer than two weeks [17]. In a prospective study of 15,500 CABG patients over a five year period, it was shown that dialysis dependent patients with CABG had higher risk of in-hospital mortality as compared to non- dialysis dependent CABG patients (12.2% as compared to 3.1%) and also significantly higher risk of mediastinitis (3.6 vs. 1.2%) [18].

One of the largest initial studies on CABG outcomes in ESRD patients 13 years ago was a retrospective study on 82 patients in which patients had a mean follow-up of 3 years. 18.5 % of the patients had left ventricular ejection fraction (LVEF) <0.45 and the aortic cross clamp time was fairly good at 50 ± 3 minutes [10]. Mean number of grafts was 2.3. Sixty-two per‐ cent of patients received left internal mammary grafts. In this study, 30-day mortality rate was 14.6%, and the mean survival rate at one, three and five years was 71%, 56% and 39% respectively. Thirty day mortality was 14.6% due to a variety of causes including myocardial infarction, cardiac arrest or cardiac tamponade. This study showed that although there was high peri and post- operative as well as long term mortality in ESRD patients undergoing CABG, there was a significant improvement in functional status as a result of CABG. The use of internal mammary artery grafts was related with less in-hospital mortality as well. Perioperative atrial fibrillation occurred in 12.1 % of patients within the first thirty days. With patients having preoperative Newyork Heart Association (NYHA) class III or class IV symptoms, LVEF less than 45% and age greater than 60 years, there was higher long term mortality. The incidence of post- operative bleeding and sternal infection was 3.6% which

Patients with CKD have a poor baroreceptor reflex. Therefore, they do not adjust very well in conditions like post-operative hypotension. Therefore, poor cardiac output can be more

In a study of 2438 CKD patients undergoing CABG over a three year period, operative mor‐ tality was 4.8% in individuals with stage 3 CKD and 7.1% in individuals with stage 4–5 CKD while it was 2.2% in those without significant CKD [20]. CKD was associated with increased post-operative blood transfusion requirement, acute kidney injury superimposed on CKD,

mg/dl, as compared to 64.7 +/- 13.8 mL/min per 1.73 m2 in

**2.4. Hard endpoints after CABG**

440 Artery Bypass

57.9+/-17.6 mL/min per 1.73 m2

those who survived at an average follow-up for 2.3 years [16].

was higher when compared to patients not on dialysis.

symptomatic in this group of patients [19].

Diabetes is present in almost one third of CKD patients undergoing CABG and is considered a strong predictor of mortality in this patient group [23,24].

Szabo et al showed in a study of 2779 CABG patients that in 19.4% of patients with diabetes, the cross-clamp and cardiopulmonary bypass times as well as the need for inotropic sup‐ port, transfusion of blood products and progression of renal failure were all higher in pa‐ tients with CKD. Additionally, the incidence of post-operative stroke was greater in diabetic patients (4.3% vs. 1.7%). Five year survival rate was 84.4% in diabetic group while it was 91.3% in the non- diabetic group [25]. Another study showed that diabetes was an inde‐ pendent major predictor of morbidity and mortality in CABG patients. In 12,198 patients, it was observed that the diabetic group had higher rates of post-operative mortality (3.9% vs. 1.6%) and stroke (2.9% vs. 1.4%). The five and ten year survival rates were 78% and 50% among patients with diabetes as compared to 88 and 71% in the non-diabetic group [26]. Morris et al demonstrated in a study of 5654 patients undergoing CABG that the five year survival rate for diabetic patients was 80% as compared to 91% for non- diabetics [27]. Out‐ comes of CABG are improved in diabetic patients who undergo grafting of internal mam‐ mary arteries, with two being better than one. In a retrospective analysis of 4382 patients undergoing CABG, it was shown at 10 year follow-up that bilateral internal mammary ar‐ tery grafting in addition to SVGs in diabetic patients improved survival and decreased need for revascularization compared with single internal mammary artery grafting along with SVGs [28]. The strong correlation between diabetes and cardiovascular outcomes including survival and myocardial infarction is due to the diffusely extensive and rapidly progressive nature of atherosclerotic coronary artery disease (CAD) in this group of patients. Various other factors such as oxidized low-density lipoproteins (LDL), hyperglycemia causing ad‐ verse metabolic shifts, deranged fibrinolysis, increased coagulability, and advanced reno‐ vascular hypertension resulting in change in vessel architecture also contribute to the progressive nature of CAD in diabetics. There is increased tendency for LDL induced athe‐ rosclerotic plaque formation and there is greater predisposition to thrombosis due to in‐ creased blood viscosity secondary to high plasma protein levels. There is also platelet and endothelial dysfunction and increased production of thromboxane A2 and von- willebrand factor along with decreased production of prostacyclins which creates a procoagulant state. Coronary vasodilation is impaired as a result of loss of the hyperpolarizing mechanics nor‐ mally present in endothelial cells. Autonomic neuropathy in diabetes increases cardiac chrontropic workload and subsequently leads to greater oxygen demand even at rest. There is enhanced vascular tone in the coronary atherosclerotic plaque area leading to further re‐ duction in blood flow, producing orthostatic changes which leads to reduction in coronary perfusion pressure and mitigates warning signs of ischemia such as angina [27,29-32].

while intermediate and very low density lipoprotein (IDL and VLDL) levels as well as tri‐ glyceride levels were higher in dialysis patients while there was no significant difference in LDL levels [35]. In part, the role of decreased renal metabolism of lipids leads to a decreased

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

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

443

Atherosclerosis is regarded as an inflammatory process [36]. It has also been shown that in dialysis-dependent patients, oxidative stress is increased resulting in a pro-inflammatory en‐ vironment. As a result, incidence of cardiovascular events is increased. In a comparison study of 28 healthy subjects and 31 patients with renal disease, it was discovered that gluta‐ thione peroxidase and superoxide dismutase activities were increased in patients on HD while total glutathione and glutathione reductase activity is reduced resulting in increased

Renal artery stenosis (RAS) can lead to refractory hypertension and gradual deterioration in kidney function. The presence of underlying RAS and its effect on CABG outcomes has been studied and variable results have been obtained. In a study of 798 patients undergoing iso‐ lated CABG with 18.7% having renal artery stenosis (>50% stenosis), acute renal failure de‐ veloped in 10.2% of patients post procedure. The mortality rate was 14% in patients who developed acute renal failure (ARF) post operatively, while it was 0.2% in patients who did not develop ARF. However, presence of RAS was not associated with development of ARF

In a series of eighteen patients undergoing CABG who also had varying degrees of RAS with mean serum creatinine of 2.6±2.7 mg/dl, RAS was not associated with adverse out‐

Besides relatively increased short-term mortality in patients with CKD undergoing CABG, they also encounter increased morbidity from infections, blood transfusions, and stroke. In a retrospective analysis of 3954 patients where 82.7% patients had creatinine <1.5 mg/dl, and 16% had a serum creatinine level between 1.5 and 3.0 mg/dl, it was demonstrated that pa‐ tients with a serum creatinine level >1.5 mg/dl had a mortality of 7% compared to 3% in pa‐ tients with serum creatinine <1.5 mg/dl. Additionally, patients with a higher serum creatinine level had a higher incidence of requiring prolonged mechanical ventilation (15% vs. 8%), risk of stroke (7% vs. 2%), and bleeding complications (8% vs. 3%). Three infectious complications (mediastinitis, graft harvest site infection, and chest wound infections) were not different among these groups, whereas the occurrence of pneumonia and endocarditis

It is believed that the prolonged mechanical ventilation and the need for re-intubation after CABG in patients with renal dysfunction are due to a compromised ability to eliminate fluid

level of LDL is likely the cause.

*2.6.4. Impact of renal artery stenosis on CABG*

oxidative stress [37].

post-operatively [38].

comes post-operatively [39].

*2.7.1. Prolonged mechanical ventilation*

**2.7. Post-CABG complications in patients with CKD**

was significantly higher in patients with a higher serum creatinine [40].

#### *2.6.2. Hypertension*

Hypertension has also been associated with worse post CABG outcomes. In a multi centre study of 2417 patients among whom patients were categorized into patients with normal preoperative blood pressure, isolated systolic hypertension (systolic blood pressure >140 mm Hg), diastolic hypertension (diastolic blood pressure >90 mm Hg), or a combination of systolic and diastolic hypertension. It was found that isolated systolic hypertension was as‐ sociated with a 40% greater risk of adverse outcomes such as stroke, renal failure, congestive heart failure and all cause mortality after CABG. Even after correction for confounding risk factor adjustment, the increased risk of adverse outcomes was significantly more pro‐ nounced in hypertensive patients [33].

#### *2.6.3. Impact of other risk factors*

In a study of 936 hemodialysis patients to elucidate correlation of recognized risk factors in CKD patients, it was found that correlation with diabetes, smoking, African-American race and increasing age of above fifty- five years was strong. It is suspected that non-traditional risk factors like uremic environment and hemodialysis procedure using arteriovenous fistu‐ lae and high output state associated with these fistulae also impact the outcomes after CABG adversely [34].

Dyslipidemia with a high LDL is a classic risk factor for development of CAD in the general population. However, it is likely not a major risk factor in patients with advanced renal dis‐ ease. In a study of 210 dialysis dependent patients compared with 223 control subjects with normal renal function, it was found that high density lipoprotein (HDL) levels were low while intermediate and very low density lipoprotein (IDL and VLDL) levels as well as tri‐ glyceride levels were higher in dialysis patients while there was no significant difference in LDL levels [35]. In part, the role of decreased renal metabolism of lipids leads to a decreased level of LDL is likely the cause.

Atherosclerosis is regarded as an inflammatory process [36]. It has also been shown that in dialysis-dependent patients, oxidative stress is increased resulting in a pro-inflammatory en‐ vironment. As a result, incidence of cardiovascular events is increased. In a comparison study of 28 healthy subjects and 31 patients with renal disease, it was discovered that gluta‐ thione peroxidase and superoxide dismutase activities were increased in patients on HD while total glutathione and glutathione reductase activity is reduced resulting in increased oxidative stress [37].
