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Eur J Cardiothorac Surg 2001;20:565-572
© 2001 Elsevier Science NL

Coronary artery bypass grafting for patients with non-dialysis-dependent renal dysfunction (serum creatinine >=2.0 mg/dl)

Hitoshi Hirosea, Atushi Amanob, Akihito Takahashia, Naoko Naganob

a Department of Cardiovascular Surgery, Kobari General Hospital, 29-1 Yokouchi, Noda City, Chiba, 278-8501 Japan
b Department of Cardiovascular Surgery, Shin-Tokyo Hospital, Chiba, Japan

Received 9 January 2001; received in revised form 16 May 2001; accepted 31 May 2001.

Corresponding author. Tel.: +81-471-24-6666; fax: +81-471-24-6764
e-mail: genex{at}nifty.com


    Abstract
 Top
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 References
 
Introduction: Patients with renal dysfunction carry a risk of coronary atherosclerosis. The purpose of this study was to evaluate the outcome after coronary artery bypass grafting (CABG) in patients with decreased renal function (serum creatinine >=2.0 mg/dl). Methods: We retrospectively analyzed consecutive patients who had undergone isolated CABG at Shin-Tokyo Hospital between May 1, 1991 and April 31, 2000. Preoperative, perioperative, and follow-up data of the non-dialysis-dependent patients with preoperative serum creatinine equal to or more than 2.0 mg/dl (group R, n=59) were collected, and compared with those of the control patients (serum creatinine <2.0, group C, n=1666). Group R was further divided into the off-pump and on-pump CABG group and their perioperative results were compared. Results: Group R included 51 males and eight females with a mean age of 66.4. The mean number of anastomoses was not significantly different between groups; however, clump time and pump time were longer in group R. Postoperative recovery was longer in group R than in group C, which is associated with a more frequent occurrence of major complications (28.8% in group R and 10.7% in group C, P<0.0001) and mortalities (6.8% in group R and 0.5% in group C, P<0.0005). The patients who underwent off-pump CABG experienced relatively faster recovery than those who underwent on-pump CABG, despite decreased renal function. At the mean follow-up of 2.4 years, the actuarial 3-year survival rate of groups R and C were 75.3 and 96.9%, respectively (P<0.0001), excluding hospital mortality. The actuarial 3-year cardiac event-free rate was 76.7% in group R and 87.3% in group C (P<0.05). Conclusions: Patients with decreased renal function carry significant operative risks and require prolonged hospital care. Even after adequate surgical revascularization was completed, the long-term cardiac event-free and survival rates in the patients with renal dysfunction were inferior to the patients with normal renal function.

Key Words: Coronary artery disease • Renal failure • Long-term result • Coronary artery bypass graft


    1. Introduction
 Top
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 References
 
Coronary artery disease is a major cause of death in patients with renal dysfunction. Among the patients who undergo coronary artery bypass grafting (CABG), renal dysfunction is known to be a major predictor of in-hospital and remote mortality [1,2]. Hemodialysis may modify the perioperative and/or remote outcomes [38]. However, there have only been a few reports on patients with renal dysfunction independent from hemodialysis [912], and the prognosis in these particular patients is not well studied. This study investigated the outcome in patients with renal dysfunction (serum creatinine >=2.0 mg/dl) without hemodialysis at the time of CABG.


    2. Method
 Top
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 References
 
A total of 1725 consecutive patients, who were not supported by hemodialysis, underwent isolated coronary artery bypass grafting (CABG) at Shin-Tokyo Hospital between May 1, 1991 and April 31, 2000. Among them, there were 59 patients (3.4%) with renal dysfunction (group R), which was defined by preoperative serum creatinine >=2.0 mg/dl. The other 1666 patients were included in the control group (group C, preoperative serum creatinine <2.0 mg/dl). Patients on either hemodialysis or peritoneal dialysis were excluded from this study.

CABG was performed under cardioplegic arrest using St. Thomas solution, supported with cardiopulmonary bypass (CPB) at normothermia (36°C). In late 1996, off-pump CABG under the beating-heart was introduced and selected patients underwent off-pump CABG [13]. Group R was further divided into two groups: the on-pump (n=43) group and the off-pump group (n=16).

Patients' demographics, operative data, postoperative complications and remote results were collected. Preoperative risk factors and postoperative complications were defined according to the criteria of the Society of Thoracic Surgeons. Hospital mortality included death occurring within 30 days of the operation or during the same hospitalization. Remote cardiac events included: recurrence of angina (symptomatic angina or positive treadmill test), percutaneous transluminal coronary angioplasty (PTCA), redo CABG, congestive heart failure (CHF), arrhythmia requiring hospital admission and sudden death. Remote results were collected by correspondence with patients or reports from the private physicians. Patients in group R were contacted by telephone and their functional status was recorded.

Statistical analysis was performed using Student's t-test for continuous variables or chi-square tests (Fisher's exact tests if n<5) for categorical variables. Results were expressed as the mean±standard deviation. Postoperative patient survival and event-free rate were constructed by the Kaplan–Meier method, and compared using Mantel–Cox's log-rank tests. Relative risk (RR) was calculated by logistic regression analysis and expressed with 95% confidence interval (CI). A P-value less than 0.05 was considered significant. All statistical analyses were performed using Statview version 5.0 (SAS Institute, Cary, NC, USA).


    3. Results
 Top
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 References
 
3.1. Patients' demographics
Group R consisted of 59 patients (51 males and eight females with a mean age of 66.4±8.2 years), and group C consisted of 1666 patients (1280 males and 386 females with a mean age of 64.3±9.4 years). The preoperative data are described in Table 1. The causes of renal dysfunction were diabetes in 29 (49.2%), hypertension in 11 (18.6%), atherosclerosis in 8 (13.6%), glomerulonephritis in 5 (8.8%), and others or unknown in 6. Angiographical profiles in group R were similar to group C; however, the patients in group R had more frequent preoperative co-morbidities such as hypertension, insulin use for diabetes, CHF, atrial fibrillation, calcified aorta, peripheral vascular disease and emergent surgery.


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Table 1. Preoperative risk factors

 
3.2. Operative results
Operative data are shown in Table 2. Since future induction of hemodialysis was anticipated, harvest of the radial artery was avoided intentionally. Two patients in whom the radial artery was harvested were redo cases and there was a lack of grafts available due to previous surgery. Because the radial artery was preserved in most of the cases in group R, the saphenous vein was more frequently used instead, and total arterial bypass was less frequently achieved in group R than in group C. In group R, blood was transfused more often than in group C.


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Table 2. Surgical results

 
3.3. Postoperative results
The postoperative course is displayed in Table 3. Group R required a longer intubation period, longer ICU stay, and longer postoperative hospital stay than group C. Major complications were more often observed in group R (28.8%) than in group C (10.7%), with P <0.0001. In group R, postoperative hemodialysis was performed in eight patients (13.6%). Among them, one patient required long-term maintenance hemodialysis, and the others required hemodialysis in the immediate postoperative period only. Prolonged ventilator support was necessary more often in group R. The hospital mortality rates of group R and group C were 6.8 and 0.5%, respectively (P<0.0005). The causes of the in-hospital deaths in group R were pneumonia in two, ischemic bowel in one, and mediastinitis in one. There were no cardiac-related hospital mortalities in group R.


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Table 3. Postoperative outcomes

 
3.4. Risk factor analysis
Preoperative risk factors, listed in Table 1 as well as the selection of the grafts (arterial vs. venous grafting) and methods of surgery (off-pump vs. on-pump), were entered into logistic regression analysis in order to identify the predictors of in-hospital death. By univariate analysis, significant predictors of in-hospital death included: renal dysfunction (preoperative serum creatinine >=2.0 mg/dl, RR 15.07, 95% CI 4.40–51.57), age over 75 years (RR 3.82, 95% CI 1.27–11.45), acute myocardial infarction (AMI, RR 19.09, 95% CI 6.55–55.64), unstable angina (RR 4.62, 95% CI 1.59–13.44), history of CHF (RR 16.50, 95% CI 5.13–53.05), chronic obstructive pulmonary disease (RR 6.08, 95% CI 1.66–22.27), atrial fibrillation (RR 11.25, 95% CI 3.43–36.91), aortic calcification (RR 7.34, 95% CI 2.51–21.43), emergent surgery (RR 44.89, 95% CI 12.37–162.91), and redo CABG (RR 6.03, 95% CI 1.31–27.72). Further multivariate analysis of these parameters revealed the isolated predictors of in-hospital death, which were renal dysfunction, CHF, atrial fibrillation, aortic calcification, and redo CABG.

3.5. Long-term cardiac events
Excluding hospital mortalities, the collection of long-term data was completed in 96.4% of patients in group R with a mean follow-up period of 2.4±1.9 years, and 95.2% of patients in group C with a mean follow-up period of 2.5±1.9 years. The remote cardiac events are listed in Table 4 and the long-term cardiac event-free curve is displayed in Fig. 1 . The actuarial 1-, 2-, 3-, and 4-year event-free rates were 85.7, 80.4, 76.7, and 72.8 in group R and 96.8, 90.7, 87.3, and 83.4 in group C, showing significant difference (P<0.05). Among the survivors in group R, the functional status of the patients was determined according to New York Heart Association (NYHA) class, which was identified as class I in 37 (69.8%), class II in 5 (13.5%), class III in 5 (13.5%), and class IV in 1 (2.7%). Analysis of the late cardiac events revealed that CHF occurred more frequently in group R than in group C, but that the recurrence of angina was less frequent in group R. By univariate analysis, the predictors of late cardiac events were included: renal dysfunction (RR 1.80, 95% CI 1.01–3.22), acute myocardial infarction (AMI, RR 1.95, 95% CI 1.24–3.06), poor left ventricular function (RR 2.52, 95% CI 1.76–3.62), and CHF (RR 2.18, 95% CI 1.60–2.98). Further multivariate study revealed independent predictors, which were AMI, poor left ventricular function, and CHF. In group R, eight patients (15.0%) required late chronic dialysis.


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Table 4. Remote results

 


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Fig. 1. Long-term cardiac event-free curve, constructed using Kaplan–Meier method. The black line indicates patients with renal dysfunction and the gray line indicates control patients. The cardiac event-free rate of the renal dysfunction group was significantly inferior to that of the control patients (P<0.05).

 
3.6. Long-term survivals
Late death was observed in 16 patients (30.2%) in group R, which was significantly greater than that in Group C (4.2%), P<0.001 by the chi-square test. Cardiac death was observed in five (9.4%) in group R, which was significantly more frequent than in group C. Among the 11 non-cardiac deaths in group R, two deaths were directly related to renal dysfunction. The survival curve of each group is shown in Fig. 2 . The actuarial 1-, 2-, 3-, and 4-year survival rates were 88.2, 81.4, 75.3, and 71.8% in group R and 99.4, 98.7, 96.9, and 94.5% in group C, which was significantly different by Kaplan–Meier analysis (P<0.001). The predictors of late death were renal dysfunction (RR 7.46, 95% CI 4.23–12.89), AMI (RR 2.43, 95% CI 1.25–4.69), previous myocardial infarction (RR 1.968, 95% CI 1.16–3.34), poor left ventricular function (RR 5.07, 95% CI 3.19–8.05), CHF (RR 3.81, 95% CI 2.45–5.92), diabetes mellitus (RR 1.65, 95% CI 1.09–2.50), insulin user (RR 2.28, 95% CI 1.29–4.03), aortic calcification (RR 2.31, 95% CI 1.38–3.88), and redo CABG (RR 2.96, 95% CI 1.20–7.33). Multivariate analysis revealed independent predictors of late death including: renal dysfunction, AMI, poor left ventricular function, CHF, and calcified ascending aorta.



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Fig. 2. Long-term survival curve, constructed using the Kaplan–Meier method. The black line indicates patients on hemodialysis and the gray line indicates control patients. The survival rate of the renal dysfunction group was significantly inferior to that of the control patients (P<0.0001).

 
3.7. Off-pump CABG
In group R, off-pump CABG was performed in 16 patients and on-pump CABG in 43 patients. The preoperative risk factors between off-pump and on-pump CABG were similar except for the higher frequency of hypertension in the off-pump group (Table 1B). Off-pump CABG was performed more often in group R (21.7%) than in group C (16.3%). The surgical data are shown in Table 2B. The number of distal anastomoses performed by off-pump CABG was significantly fewer than in on-pump CABG. The frequency of the arterial bypass was not significantly different between the off-pump and on-pump groups; however, the frequency of use of saphenous vein graft was significantly lower in the off-pump group. Requirement of blood transfusion was markedly lower in the off-pump group. The postoperative results are shown in Table 3B. The intubation period was not significantly different between the off-pump and off-pump groups; however, the ICU stay and postoperative stay were significantly shorter in the off-pump group than in the on-pump group. The ICU stay for patients who underwent off-pump CABG was less than half of that of patients who underwent on-pump CABG, and the length of postoperative stay was two thirds that of the on-pump group. No postoperative stroke, perioperative myocardial infarction, low-output syndrome, or re-exploration for bleeding occurred in the off-pump group. During the mean follow-up of 1.5 years in the off-pump group, two incidences of CHF including one death were observed. Although the length of follow-up in the off-pump group was limited, no significant differences were identified in terms of the long-term survival or cardiac event-free rate between the two groups.


    4. Discussion
 Top
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 References
 
4.1. Patients' profile
Due to poor water clearance, a history of CHF was frequently observed in the patients with decreased renal function. Alternation of calcium metabolism in patients with renal insufficiency may contribute to the frequent observations of calcified aorta in group R. We also considered that renal anemia probably increased the need for transfusion.

4.2. General surgical technique
Complete revascularization using arterial conduits has been reported to provide superior postoperative and remote results, compared to revascularization using vein graft [14]. Our strategy of CABG is complete revascularization using the arterial conduits if possible. The selections of grafts were varied; however, in our practice, usually the left anterior descending artery (LAD) was bypassed with one of the internal mammary arteries, the right coronary artery with the gastroepiploic artery, the circumflex artery with the left internal mammary artery, the radial artery, or the saphenous vein. The use of bilateral internal mammary artery should be avoided for the patients with uncontrolled diabetes due to the risk of postoperative sternal wound complication. Since hemodialysis blood access is usually established in the radial artery, the radial artery should not be selected as a graft conduit if the patient has elevated serum creatinine. Although the aim was total arterial revascularization, due to the lack of conduits or the presence of uncontrolled diabetes, saphenous vein graft was used in two thirds of the patients in our series.

In on-pump CABG in the patients with renal dysfunction, we maintained the perfusion pressure above 60 mmHg, preferably above 70 mmHg to preserve renal perfusion. Frocemide and mannitol were given in order to increase urine output. Ultrafiltration was added to remove excess water during CPB. Hyperkalemia and acidemia were the indications for use of intraoperative hemodialysis.

4.3. Off-pump CABG
After the introduction of off-pump CABG, the patients with renal dysfunction were more often referred to off-pump CABG. Before 1997, all patients in group R underwent on-pump CABG; however, after 1998, supported by the initial good results of off-pump CABG [15], patients with decreased renal dysfunction were favorably referred for off-pump CABG unless there were contraindications for off-pump CABG, such as intramuscular coronary artery or severely calcified coronary artery. After 1998, 69.9% (16 out of 23) of renal patients underwent off-pump CABG.

The results in our study show the patients who underwent off-pump CABG demonstrated earlier recovery, compared to the patients who underwent on-pump CABG. In off-pump bypass, the perfusion pressure is physiological and is much higher than the pressure created by CPB. Since renal perfusion pressure was well maintained during the entire operation, urine output would be preserved as well. Dilutional anemia when using CPB does not occur in off-pump bypass and the frequency of blood transfusion was much lower than in on-pump CABG. Calcified aorta, frequently observed in patients with renal dysfunction, was considered to be the risk factor of postoperative stroke. Since cannulation to the ascending aorta is not required in off-pump CABG, we speculated that the risk of postoperative stroke was lower. We have performed more than 100 off-pump CABG and encountered no postoperative strokes [13]. The postoperative recovery of the renal patients who underwent off-pump CABG was significantly faster than that of those who underwent on-pump CABG. Off-pump CABG successfully contributed to reduce the length of stay to a level similar to that of patients with normal renal function. Thus, we considered that off-pump CABG successfully contributed to the reduction of the length of stay.

The number of distal anastomoses in the off-pump group was significantly smaller than that in the on-pump CABG group. In the early phase of this study, using a compression type of coronary stabilizer, the indication of off-pump CABG was limited to the revascularization of the anterior surface of the heart. However, after mid-1999, the suction type of stabilizer was introduced to our institute, which allowed us to perform multivessel revascularization including the posterior wall of the heart. The number of distal anastomoses in off-pump CABG was increased from 1.9±0.4 with the compression device to 2.4±0.7 with the suction device. The percentage of complete revascularization also increased from 44.4% in the early phase using the compression device to 85.7% in the late phase using the suction device. Thus the introduction of the new device may have influenced the occurrence of the cardiac events in the off-pump group. To clarify the remote benefit of off-pump CABG, a longer follow-up study is necessary.

4.4. Early results
Due to impaired water clearance, postoperative hypoxia secondary to pulmonary congestion was often observed. The metabolism of anesthetic medication in patients with renal dysfunction is delayed and the effect of anesthesia might be prolonged. These two factors might result in a delay in extubation and a delay in transfer out of ICU. Postoperative hemodialysis was indicated if the patient developed anuria, which is refectory to diuretics or inotropic support, and/or if the patient had elevated serum potassium. Three out of the six patients who required prolonged ventilator support in our study were hemodialyzed in ICU. If hemodynamics were well preserved during hemodialysis, the patient's urine output eventually would improve and the patient might become independent of hemodialysis. However, patients with unstable hemodynamics due to low-output syndrome and hemodialysis-dependent patients all died in ICU. Preoperative creatinine in patients who received postoperative hemodialysis was 3.8±1.1 mg/ml, which was significantly higher than in the patients with renal dysfunction who were not hemodialyzed postoperatively (2.5±0.7 mg/ml, P<0.001).

The reported mortality rates in patients with non-dialysis-dependent renal dysfunction were between 5.3% [11] and 19.3% [10]. Our hospital mortality rate in group R was significantly higher than that in the control group; however, it was comparable to these previous reports. Elevated serum creatinine (2.0 mg/dl) was the independent predictor of in-hospital death.

4.5. Long-term results
Even after surgical revascularization, late cardiac events occurred and would be a problem in patients with renal dysfunction. Angina recurrence and the incidence of remote PTCA were controlled adequately by CABG in group R. However, CHF occurred more frequently in patients with renal dysfunction, which may be related to poor water clearance due to renal disease.

Postoperative angiography was not routinely performed in the renal patients, since angiography for the patients with decreased renal function may result in the necessity for hemodialysis after the procedure. Thus, asymptomatic patients were reluctant to undergo postoperative angiography. Asymptomatic coronary ischemia may be overlooked and it may be related with the small incidence of postoperative PTCA in group R; in addition, it may have attributed to the increased incidence of cardiac death in group R.

Long-term survival was poor in group R and renal dysfunction was identified as an isolated predictor of remote death. Long-term survival after CABG in patients with non-dialysis-dependent renal dysfunction has been poorly studied. Durmaz et al. [11] followed non-dialysis-dependent patients with various degrees of renal function and reported a 3-year survival rate of 96% in patients with creatinine between 1.6 and 2.5 mg/dl and 57% in patients with creatinine >2.5 mg/dl. The 3-year survival of the patients in our study was 75.3% and preoperative creatinine >=2.0 mg/dl was the independent predictor of late death. Both cardiac and non-cardiac deaths were frequent in patients with renal dysfunction. Four out of five cardiac deaths in group R were due to CHF. Once CHF occurs after CABG in patients with decreased renal function, it may be fatal and special care should be taken.

Diabetes mellitus is known to influence long-term mortality [16,17]. Patients with diabetic nephropathy are reported more likely to develop cardiovascular complications than those whose renal dysfunction is due to other causes [18]. To eliminate the influence of diabetes, a total of 971 (25 in group R and 946 in group C) non-diabetic patients in our series were identified and completed late follow-up. Among these subsets, the 3-year survival rates were 81.1% in group R and 98.1% in group C with P<0.0001, supporting the hypothesis that renal dysfunction is an isolated predictor of long-term death.

4.6. Study limitations
The annual sample size in group R was small. Changes in the strategy of CABG, such as induction of off-pump CABG or induction of new devices, may have influenced both postoperative and remote results. Due to the recent adaptation of off-pump CABG, its long-term results remained unknown although its short-term results were favorable.

Our study was performed in a single institute with a single surgical group, which may bias the operative data. Our hospital is ultimate cardiac center and the majority of the patients were referred from outside of the hospital. Only 25% of the patients were followed up at our outpatient clinic; the others were followed up by local hospitals or private cardiologists, which might have influenced the late results.

Serum creatinine was chosen for the detection of renal dysfunction because of the simplicity of its measurement. Ideally, creatinine clearance should be measured to assess renal function, since serum creatinine levels are influenced by body surface area and body water mass. Thus, in older patients, patients with serum creatinine 1.5–1.9 mg/dl might be a sign of significant renal dysfunction, which was not detected in this study.

4.7. Summary
CABG in patients with renal dysfunction can be performed with certain perioperative risks. Even after CABG, patients with renal dysfunction should be carefully monitored. Care should be taken to detect the early development of CHF. Off-pump CABG for patients with deceased renal function is safe and contributes to shorten the patient's recovery period; however, the remote results are not available at this time.


    References
 Top
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 References
 

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G. S. Hillis, B. L. Croal, K. G. Buchan, H. El-Shafei, G. Gibson, R. R. Jeffrey, C. G.M. Millar, G. J. Prescott, and B. H. Cuthbertson
Renal Function and Outcome From Coronary Artery Bypass Grafting: Impact on Mortality After a 2.3-Year Follow-Up
Circulation, February 28, 2006; 113(8): 1056 - 1062.
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J. Thorac. Cardiovasc. Surg.Home page
R. M.A. van de Wal, B. L. van Brussel, A. A. Voors, T. D.J. Smilde, J. C. Kelder, H. A. van Swieten, W. H. van Gilst, D. J. van Veldhuisen, and H.W. T. Plokker
Mild preoperative renal dysfunction as a predictor of long-term clinical outcome after coronary bypass surgery
J. Thorac. Cardiovasc. Surg., February 1, 2005; 129(2): 330 - 335.
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Ann. Thorac. Surg.Home page
M. Tabata, S. Takanashi, T. Fukui, T. Horai, T. Uchimuro, K. Kitabayashi, and Y. Hosoda
Off-Pump Coronary Artery Bypass Grafting in Patients With Renal Dysfunction
Ann. Thorac. Surg., December 1, 2004; 78(6): 2044 - 2049.
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Eur. J. Cardiothorac. Surg.Home page
P. E. Antunes, D. Prieto, J. F. de Oliveira, and M. J. Antunes
Renal dysfunction after myocardial revascularization
Eur. J. Cardiothorac. Surg., April 1, 2004; 25(4): 597 - 604.
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J Am Coll CardiolHome page
C. M. Gibson, D. S. Pinto, S. A. Murphy, D. A. Morrow, H.-P. Hobbach, S. D. Wiviott, R. P. Giugliano, C. P. Cannon, E. M. Antman, E. Braunwald, et al.
Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality
J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1535 - 1543.
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J. Am. Soc. Nephrol.Home page
C. A. Herzog
How to Manage the Renal Patient with Coronary Heart Disease: The Agony and the Ecstasy of Opinion-Based Medicine
J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2556 - 2572.
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Ann. Thorac. Surg.Home page
I. Durmaz, T. Yagdi, T. Calkavur, R. Mahmudov, A. Z. Apaydin, H. Posacioglu, Y. Atay, and C. Engin
Prophylactic dialysis in patients with renal dysfunction undergoing on-pump coronary artery bypass surgery
Ann. Thorac. Surg., March 1, 2003; 75(3): 859 - 864.
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