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Ann Thorac Surg 2006;81:1379-1384
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Cardiac Surgery in Renal Transplant Recipients: Experience from Washington Hospital Center

Li Zhang, MD, Jorge M. Garcia, MD*, Peter C. Hill, MD, Elizabeth Haile, MS, Jimmy A. Light, MD, Paul J. Corso, MD

Section of Cardiac Surgery, Department of Surgery, Washington Hospital Center, Washington, DC

Accepted for publication November 3, 2005.

* Address correspondence to Dr Garcia, Section of Cardiac Surgery, Department of Surgery, Washington Hospital Center, 110 Irving Street, NW, Washington, DC 20010-2975 (Email: jorge.m.garcia{at}medstar.net).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Background: The number of renal transplant survivors requiring surgical treatment for cardiovascular diseases is increasing. A retrospective study was conducted to determine the outcomes of renal transplant recipients undergoing cardiac surgery.

Methods: Fifty-seven renal transplant recipients whose cardiac surgery was performed between 1987 and 2004, and whose allograft was functioning at the time of cardiac surgery, were identified. We analyzed postoperative mortality and morbidity as well as late mortality.

Results: Among 57 patients, 70.2% had hypertension, 54.4% diabetes, and 28.1% poor left ventricular function (ejection fraction < 0.35). Preoperative renal insufficiency (serum creatinine level ≥ 3 mg/dL) was noted in 12.3% of the patients. Coronary artery disease was the dominant indication for the surgery. The median interval from renal transplant to cardiac surgery was 60 months. In-hospital mortality was 5.3%. All deaths were cardiac-related. Infectious complications occurred in 17.5% of the patients. Acute allograft failure requiring hemodialysis occurred in 28.6% of the patients with preoperative renal insufficiency, more frequent than those without preoperative renal insufficiency. Multivariable analysis identified preoperative renal insufficiency, mitral valve disease, and left ventricular dysfunction as independent predictors of in-hospital major adverse events (including death, infection, and renal failure). The 3-year survival was 71% after a median follow-up of 34 months.

Conclusions: Infection control and renal protection should be stressed to ensure the safety of cardiac surgery in this patient group, while preoperative renal insufficiency, mitral valve disease, and left ventricular dysfunction are associated with early adverse outcomes. In the renal transplant recipients undergoing an isolated CABG, avoidance of cardiopulmonary bypass and use of arterial grafts might lead to better outcomes.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
In the United States there are more than 100,000 people with functioning renal transplants; in 2002 alone, 15,712 renal transplantations were performed [1]. The combination of advances in surgical techniques, organ preservation, and immunosuppressive agents has improved short-term and long-term survival of transplant recipients. However, the majority of the recipients are living with multiple comorbidities and chronic immunosuppression, which contribute to the development of coronary artery disease. Long-term steroid use is known to accelerate coronary atherosclerosis. Moreover, immunosuppressive therapy increases the risk of cardiovascular system infection. Subsequently, a significant number of survivors will need surgical intervention for their cardiovascular diseases. Numerous case reports on cardiac surgery after renal transplantation have been published since Menzoian and colleagues [2] performed coronary artery bypass grafting (CABG) on a renal transplant recipient in 1974. However, information is lacking on the perioperative management and postoperative outcomes of these patients.

In this article we present our experience in treating the renal transplant recipients referred for cardiac surgery at the Washington Hospital Center over the last two decades. In the study we investigated the impact of renal transplantation on the mortality of cardiac surgery, the risk of early infection, and the risk of allograft injury after cardiac surgery.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Acknowledgments
 References
 
Patients
This was a single-institution retrospective study, approved by the Institutional Review Board of the MedStar Research Institute in January 2005. The computerized database of the Section of Cardiac Surgery was used to identify all patients with previous renal transplants who underwent cardiac surgery at the Washington Hospital Center between January 1987 and December 2004. Those with allograft failure requiring regular hemodialysis before cardiac surgery were excluded. Baseline, intraoperative and postoperative outcome variables were recorded and entered in this cardiac surgery research database by a dedicated data-coordinating center. All adverse clinical events were source-documented and adjudicated.

Consultation
The transplant team and/or nephrologists were consulted as necessary. Preoperative medications were administered until the morning of the surgery.

Surgery
Standard surgical techniques and cannulation were used. An off-pump approach was attempted in selected cases if only CABG was indicated. When cardiopulmonary bypass was applied, cold blood cardioplegia was used, perfusion pressure was maintained between 60 and 70 mm Hg, and urine output was closely monitored through the surgery. Vasoconstrictors were used as indicated. Activated clotting times were between 480 and 600 seconds as recommended for routine practice. Intraoperative use of epsilon-aminocaproic acid was the standard of care in our institution during the study period. Aprotinin was rarely used in light of its adverse impact on renal function. Mannitol or furosemide was administered during the surgery to encourage diuresis.

Postoperative Support
Inotropes, including dopamine and/or dobutamine, were used routinely in the immediate postoperative period to stabilize hemodynamics. Diuretics were administered to maintain an adequate urine output, given that hydration and renal perfusion were satisfactory. Nephrotoxic medications were prohibited. Renal function was closely monitored in all patients until discharge. Pulse steroids were initiated for graft rejection.

Immunosuppression Therapy
Oral immunosuppressive medications were continued until the morning of the surgery for all patients. The next dose was administered orally or through a nasogastric tube the day after surgery. A stress dose of steroids was initiated at the time of the surgery. The dose of immunosuppression regimen was adjusted according to serum drug levels. If acute renal failure was suspected on the basis of a decreasing urine output or an increasing serum creatinine level, the dose of immunosuppressive medication was adjusted accordingly.

Antibiotics
Prophylactic antibiotics were used postoperatively for 24 hours in our institution. Prolonged administration of antibiotics was indicated under certain conditions; eg, endocarditis.

Renal Function Assessment
Serum creatinine level was measured preoperatively as baseline, and daily beginning on the morning after surgery as part of routine laboratory investigations until stabilization or until discharge.

Long-Term Follow-Up
The patients whose renal transplant was performed at Washington Hospital Center were followed by transplant service. The online Social Security Death Index (ssdi.genealogy.rootsweb.com), accessed on October 4, 2005, was used to identify late deaths in those who were not followed by transplant service.

Statistical Analysis
Data were expressed as number and percentages, as mean plus standard deviation, or as median with range (minimum, maximum). Continuous variables were compared using the Student t test for independent samples and p values of 0.05 or less were considered significant. Actuarial analysis of long-term survival was performed using the Kaplan-Meier method.

Multivariable Analysis
The outcome of interest that was analyzed through a multivariable model was in-hospital major adverse events (MAE), which included death, major infectious complications, and allograft failure requiring temporary or permanent hemodialysis. Predictors of in-hospital MAE were identified by multivariable logistic regression analyses. Variables reported previously as important determinants of the outcomes of interest were included in a multiple logistic regression analysis. The odds ratio from this analysis was used as a measure of the relative risk. An analysis testing for strong linear dependencies among the explanatory variables was performed using tolerance and the variance inflation factor prior to running the logistic regression. Model fit was evaluated using the Hosmer and Lemeshow goodness-of-fit statistic, as well as residual diagnostics (deviance and dfBetas) analysis. The C-statistic was reported as a measure of predictive power. All statistical analysis was performed with SAS Version 8.2 (SAS Institute Inc, Cary, NC).

Repeated Measures Analysis
The mixed model repeated measures analysis (PROC MIXED) in SAS was used to compare the preoperative creatinine level with the postoperative levels at five different time points, in order to include the subjects who have less than five measurements into the final analysis.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Acknowledgments
 References
 
Preoperative Clinical Characteristics
A total of 57 patients with functioning kidney transplants underwent cardiac surgery between 1987 and 2004. Their preoperative characteristics are shown in Table 1. Mean age was 55.4 ± 11.5 years. Most patients had a history of hypertension (70.2%) or diabetes mellitus (54.4%). Moderate or severe left ventricular dysfunction with an ejection fraction (EF) of less than 0.35 was present in 16 patients (28.1%). Sixteen patients (28.1%) had a history of congestive heart failure (CHF). All patients received immunosuppression therapy until the time of surgery, and steroids were the most common immunosuppressive agent. Mean preoperative creatinine level was 2.21 ± 1.48 mg/dL. Among 54 patients whose preoperative creatinine level was recorded, 13% had chronic renal insufficiency (defined as serum creatinine > 3 mg/dL) before the cardiac surgery.


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  		Table 1 Patient Preoperative Demographics
 
Ninety three percent of patients with coronary artery disease (40/43) had multiple vessel disease, which often involved the left anterior descending artery. A little over one third (16/43) had a history of myocardial infarction. Four patients were diagnosed as bacterial endocarditis preoperatively and all (4/4) had aortic valve involvement, while mitral valve was involved in one (1/4). The pathogens of endocarditis were staphylococcus and enterococcus.

Intraoperative Characteristics
The most common surgical procedure was CABG, followed by aortic valve replacement, aortic root replacement, mitral valve replacement, mitral valve repair, and tricuspid valve repair. More than one third (22/57) of cardiac surgeries were urgent cases, while only 2 patients underwent emergent procedure. Forty-seven out of 57 procedures were performed with cardiopulmonary bypass (82.5%). Among them, mean bypass time was 100.8 ± 54.99 minutes, mean cross-clamping time was 73.8 ± 48.21 minutes, and mean lowest core temperature during bypass was 31.7 ± 2.88°C. Internal mammary grafts (IMG) were used in 79.1% of the patients undergoing CABG with or without other procedures.

In-Hospital Mortality
Three patients died during their admissions for the cardiac procedure (in-hospital mortality: 5.3%). All three patients had preoperative immunosuppression with steroids. None of them had renal insufficiency (serum creatinine > 3 mg/dL) before the procedure. Two underwent isolated CABG. One was a 68-year-old male, who presented with triple-vessel disease, unstable angina, history of hypertension, and congestive heart failure, and mildly impaired left ventricular function. During the surgery, he was found to have diffuse coronary disease and his right coronary artery was ungraftable. The second patient was a 52-year-old male, with history of diabetes and severely impaired left and right ventricular function (EF = 0.20), undergoing urgent CABG for his triple-vessel disease. The third patient was a 63-year-old male with a history of hypertension, hypercholesterolemia, and stroke, undergoing emergent replacement of aortic root with valve conduit for type I aortic dissection. All deaths occurred within 30 days of cardiac surgery and were cardiac-related. All developed acute allograft failure before death, as part of multiple system organ failure.

Infectious Complications
Infectious complications, documented after the primary procedures, included new-onset endocarditis, mediastinitis, pulmonary infection, urinary tract infection, septicemia confirmed by blood culture, leg wound infection, and sinusitis. Overall, 16 infectious events occurred in 10 out of 57 patients after the primary procedure (17.5%) (Table 2).


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  		Table 2 Postoperative Morbidities
 
Renal Function
Eight patients (14.0%) developed severe renal failure requiring hemodialysis after the cardiac surgery, all of which were performed with cardiopulmonary bypass. Of these eight patients, three died of cardiac-related causes in the hospital. Among the five survivors requiring hemodialysis postoperatively, two patients had permanent allograft failure. Excluding 3 deaths whose renal failure resulted from multiple system organ failure, postoperative allograft failure occurred in 28.6% (2/7) of the patients with preoperative renal insufficiency, and in 6.4% (3/47) of the patients without preoperative renal insufficiency.

When comparing serum creatinine levels before and after the surgery, 4 patients who did not have postoperative renal failure were excluded due to missing data. Among the rest, elevation of serum creatinine levels in 45 patients who did not require postoperative hemodialysis was obvious only during the first 3 postoperative days. By contrast, in 8 patients who developed postoperative renal failure, average serum creatinine level increased continuously through the fifth postoperative day, although the differences versus baseline were statistically insignificant because of the small sample size (Table 3).


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  		Table 3 Comparison of Perioperative Serum Creatinine Levels
 
Risk Factors of In-Hospital MAE
Variables included in the logistic regression model were age, gender, case priority, diabetes, hypertension, CHF, chronic obstructive pulmonary disease, repeated procedure, endocarditis, mitral valve disease, ejection fraction, and preoperative renal insufficiency (serum creatinine > 3 mg/dL). Multivariate analysis revealed that preoperative renal insufficiency, mitral valve disease, and left ventricular dysfunction (EF < 0.35) were independent predictors of in-hospital MAE (Table 4).


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  		Table 4 Risk Factors for In-Hospital Major Adverse Events
 
On-Pump Versus Off-Pump
The early outcomes were compared between on-pump and off-pump isolated CABG in 36 patients (Table 5). The 10 off-pump CABGs resulted in zero mortality and zero allograft failure rate. Two patients died after on-pump isolated CABG. Postoperative allograft failure developed in 3 patients including the 2 deaths. The other one’s renal function improved eventually and did not require regular dialysis upon discharge.


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  		Table 5 In-Hospital Surgical Outcomes: On-Pump Versus Off-Pump
 
Repeated Cardiac Surgeries
Three patients required repeated cardiac procedures, which were performed during a second admission more than 30 days after the primary procedures. The interval between surgeries ranged from 1 month to 12 years after the primary procedure. One patient died after a repeated procedure, the primary cause of death was refractory endocarditis. Infectious complications, including postoperative endocarditis, pulmonary infection, urinary tract infection, and septicemia, were recorded in two patients. One patient developed transient renal dysfunction postoperatively.

Three-Year Mortality
Follow-up of operative survivors ranged from 1 to 151 months (median 34 months). Fifteen late deaths were identified. Three-year survival was 71%.


   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Acknowledgments
 References
 
Numerous case reports regarding the impact of renal transplant on subsequent cardiac surgery have been published. To our knowledge, this is the largest single-institution study on clinical outcomes of renal transplant recipients after cardiac surgery. Our results suggest that a history of renal transplant is likely to increase the surgical risks. The surgical outcomes of cardiac surgery in renal transplant recipients have improved dramatically over the last two decades, as summarized in a brief review of the literature in Table 6 [3–10]. In our study, the in-hospital mortality was 5.3%. All three early deaths occurred in patients with multiple preoperative comorbidities.


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  		Table 6 Clinical Studies on Outcomes of Renal Transplant Recipients Undergoing Cardiac Surgeries
 
The risk of postoperative infectious complication is always an issue in patients receiving permanent immunosuppression therapy. A high infection rate was noted by the reports of the 1980s and 1990s [6]; it is not surprising that in our study more than one sixth of the patients suffered postoperative infectious complications. Diabetes also augmented the risk of postoperative infection (22.6% in diabetic patients versus 11.1% in nondiabetic patients). Only one patient, however, developed mediastinitis, which occurred more frequently in an earlier report [6].

Chronic renal dysfunction, which may be present in the renal transplant recipients undergoing cardiac surgery, increased the risk of renal failure after cardiac surgery, which was also noted in a report from the University of Pittsburgh [6]. Even without severe renal dysfunction the allograft is vulnerable to surgical injury, and ischemia-reperfusion injury and systemic inflammatory reaction caused by cardiopulmonary bypass. The change in serum creatinine levels within 5 postoperative days indicated a significant impact of cardiac surgery on renal function. This impact, while transient in most patients, led to permanent injury of the allografts in 2 patients. Maintaining adequate renal perfusion and urine output, and adjusting immunosuppression perioperatively (especially calcineurin inhibitors) should be emphasized in this group of patients to prevent allograft injury. A red flag should be raised upon continuous increase of serum creatinine level beyond the third postoperative day.

It is not surprising that preoperative renal status, mitral valve disease, and poor left ventricular function merged as independent risk factors of early surgical mortality in this population. Despite insufficient clinical evidence, we recommend early cardiac intervention before deterioration of either cardiac or renal function to reduce the surgical risks.

Previous reports exclusively focused on the outcomes of those procedures requiring cardiopulmonary bypass after renal transplant. Our study differs in that it included 10 patients undergoing off-pump CABG. These patients experienced no death, and no allograft failure requiring hemodialysis, although major infectious complications occurred in one of them. In terms of early mortality and allograft failure, avoidance of cardiopulmonary bypass may confer benefits in this patient group. Although we were unable to perform a statistical assessment because of the small sample size, we believe that in selected patients off-pump CABG is the preferred approach.

Three-year survival in our study was consistent with some groups [8, 9], but lower than others [5–7]. In a study conducted at the University of Alabama, Ferguson and colleagues [7] identified history of diabetes or hypertension as the risk factors for late death. Thus, many late deaths in the current study are likely attributed to the large number of patients with diabetes or hypertension. Whether continuous aggressive treatment of these comorbidities after cardiac surgery may improve the long-term outcome should be investigated in the future.

Last year, Herzog and colleagues [10] published a nationwide study on long-term survival of renal transplant recipients undergoing coronary revascularization in the late 1990s. In the CABG group (1,100 patients) in-hospital mortality was 5.0% for those with internal mammary grafts (IMG) and 9.4% for those without IMG. Although they were unable to adjust the results to the comorbidities (eg, left ventricular function, severity of coronary disease), Herzog and colleagues suggested using IMG tended to reduce the long-term risk of cardiac death or acute myocardial infarction, similar to the findings in the general population [11].

This study was limited by the following factors. Long-term follow-up was successful in 63% of the population. We have to rely on the National Death Registry to determine the late mortality of the rest. Thus, the comparison on long-term survival with other reports might be premature. Because of the small sample size, the results from the multivariate analysis should be interpreted cautiously. We cannot exclude the existence of other risk factors, which might become apparent with a larger sample size.

In summary, we reviewed our experience with 57 renal transplant recipients undergoing cardiac surgery. These patients comprise a unique group, and certain measures (eg, prophylactic antibiotics, maintenance of renal perfusion, and close monitoring of immunosuppression) should be stressed to improve the quality of care. Preoperative renal insufficiency, mitral valve disease, and left ventricular dysfunction are the independent predictors of early adverse outcomes in this group. Avoidance of cardiopulmonary bypass and use of arterial grafts in patients with history of renal transplantation may help to reduce the mortality and morbidity associated with surgical revascularization.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
References
 
We would like to thank Rachel Schaperow of MedStar Research Institute for editing the manuscript.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. 2004 Annual Data Report, United States Renal Data System. Available at: http://www.usrds.org. Accessed May 2005.
  2. Menzoian JO, Davis RC, Idelson BA, Mannick JA, Berger RL. Coronary artery bypass surgery and renal transplantation. a case report. Ann Surg 1974;199:63-64.
  3. Bolman RM, Anderson RW, Molina JE, et al. Cardiac operations in patients with functioning renal allografts J Thorac Cardiovasc Surg 1984;88:537-543.[Abstract]
  4. De Meyer M, Wyns W, Dion R, Khoury G, Pirson Y, van Ypersele de Strihou C. Myocardial revascularization in patients on renal replacement therapy Clin Nephrol 1991;36:147-151.[Medline]
  5. Dresler C, Uthoff K, Wahlers T, et al. Open heart operations after renal transplantation Ann Thorac Surg 1997;63:143-146.[Abstract/Free Full Text]
  6. Mitruka SN, Griffith BP, Kormos RL, et al. Cardiac operations in solid-organ transplant recipients Ann Thorac Surg 1997;64:1270-1278.[Abstract/Free Full Text]
  7. Ferguson ER, Hudson SL, Diethelm AG, Pacifico AD, Dean LS, Holman WL. Outcome after myocardial revascularization and renal transplantation. a 25-year single-institution experience. Ann Surg 1999;230:232-241.[Medline]
  8. Reddy VS, Chen AC, Johnson HK, et al. Cardiac surgery after renal transplantation Am Surg 2002;68:154-158.[Medline]
  9. Ono M, Wolf RK, Angouras DC, Brown DA, Goldstein AH, Michler RE. Short- and long-term results of open heart surgery in patients with abdominal solid organ transplant Eur J Cardiothorac Surg 2002;21:1061-1072.[Abstract/Free Full Text]
  10. Herzog CA, Ma JZ, Collins AJ. Long-term outcome of renal transplant recipients in the United States after coronary revascularization procedures Circulation 2004;109:2866-2871.[Abstract/Free Full Text]
  11. Taggart DP, D’Amico R, Altman DG. Effect of arterial revascularisation on survival. a systematic review of studies comparing bilateral and single internal mammary arteries. Lancet 2001;358:870.[Medline]



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