Title: Cardiac surgical operation after renal transplantation
Abstract: Several studies reported the impact of cardiac surgical operation on morbidity and mortality in renal transplant recipients as well as on renal graft function and safety and effect of immunosuppressant medication.1-3 However, few data are available about the risk and immunosuppressant medication in patients who undergo cardiac surgical operation after successful renal transplantation, especially in patients who underwent off pump coronary artery bypass grafting (CABG) with previous renal transplantation. This research provides important insights into the immunosuppressive management of a patient requiring valve replacement or CABG after renal transplantation during the perioperative period. METHODS Six patients (4 male, 2 female) were identified who had undergone a cardiac surgical operation after renal transplantation. Charts were reviewed for factors related to the patients’ date of renal transplantation and immunosuppression therapy. Perioperative data included indication for operation, type of procedure, date of procedure, postoperative course, and complications. The severity of coronary artery disease or heart valve disease was assessed. Coronary heart disease was assessed in 2 and heart valve disease in 4 patients. Coronary arteriography revealed marked (≥75% luminal stenosis) triple-vessel disease in one patient, double-vessel disease in one patient. Aortic valve disease was found in three patients, mitral valve insufficiency in one patient. The interval between renal transplantation and cardiac operation was (8.5±1.7) years (range, 6-10 years). The mean age of the patients at cardiac operation was (42±14) years (range, 27-66 years). The mean body weight of the patients was (58±15) kg (range 44-78 kg). The mean body area of the patients was (1.5±0.1) m2 (range 1.4-1.7 m2). All patients had functioning renal allografts with preoperative serum creatinine levels (103.7±15.1) μmol/L. The preoperative New York Heart Association functional classification was III in three patients, II in three patients. All patients continued to take immunosuppressant medication of cyclosporine 50 mg twice daily and mycophenolate mofetil 0.25 g twice daily. All patients were given oral cyclosporine 50 mg and mycophenolate mofetil 0.25 g on the morning of surgery. Four valve diseases patients were operated on using moderate systemic hypothermia (32°C) for myocardial protection. Cold potassium cardioplegia was applied. Two coronary artery diseases patients were operated without pump. Particular attention was directed intraoperatively to adequate urine output. Intravenous methylprednisolone 500 mg during surgery procedure and intravenous methylprednisolone 150 mg/d for three days starting on the day of surgery were used. All patients continued to take immunosuppressant medication of cyclosporine 50 mg twice daily and mycophenolate mofetil 0.25 g twice daily when the patients were able to take oral medications. All patients’ renal function was monitored daily. All experiments were performed at least three times, and data were expressed as mean ± standard deviation (SD) and analyzed by Student’s t test. A value of P < 0.05 was considered statistically significant. RESULTS All patients survived the operation. No patient died in the post-operative course. The cure rate was 100%. In all patients, the function of the renal allograft was not impaired by cardiac surgical operation. Two patients underwent off pump CABG and four cases underwent valve replacement. For coronary revascularization, two patients received saphenous veins for all bypasses. At the mean time, the left internal mammary artery also was used. The valve operations included aortic valve replacement (AVR) in three patients, isolated mitral valve replacement (MVR) in one patient. Mechanical heart valves were used in 2 patients in the aortic position and one patient for MVR. Bioprosthetic valve was used in one patient in the aortic position. Cardiopulmonary bypass time (CPB) was (101.3±16.7) minutes, and the aortic cross-clamping time was (75.6±9.7) minutes. Patients were extubated after one day postoperatively. The left ventricle ejection fraction before operation and after operation was (56.5±5.8)% and (63.5±4.5)% respectively (P<0.05); left ventricular end-diastolic diameter before operation was (54.5±8.5) mm, while after operation was (43.7±6.8) mm (P<0.05). Serum creatinine levels before operation and after operation were (103.7±15.1) μmol/L and (106.6±34.7) μmol/L (P>0.05). Oral cyclosporine 50 mg twice daily and mycophenolate mofetil 0.25 g twice daily were continued from the day after surgery. All patients’ renal function was monitored daily and remained stable. All patients had an uneventful recovery with normal temperature, stable cardiac function, and no obvious renal transplant rejection. Routine laboratory investigations including renal function tests were within the normal range, echocardiography and chest X-ray did not show any abnormalities, and all patients were discharged from hospital. Hospitalization time was (17±6) days. The follow-up of the 6 patients was 4-15 months. All patients were free of cardiac symptoms and returned to New York Heart Association Classes I and II. DISCUSSION We administered intravenous methylprednisolone, 500 mg during surgery and 150 mg/d for 3 days after surgery, to prevent rejection and provide anti-inflammatory and anti-allergy effects. Obviously, the risk of rejection was not enhanced when immunosuppressive therapy was maintained throughout the perioperative period. With taking long-term immunosuppressive medication, infection was the most worrying operation complication for a renal transplant recipient.4 So controlling blood glucose well and rationally using antibiotics was essential. In order to prevent the damage of cardiopulmonary bypass on renal transplant, we tried to shorten the operation time and cross-clamping time in the condition of low temperature. At the same time, we remained high perfusion pressure during the bypass, ensuring that the patient maintained urine, and patient renal function was monitored daily after operation. We had used off-pump of coronary artery disease to avoid the cardiopulmonary bypass damage. In order to avoid the danger of immunosuppressive medication, we had performed operations carefully. A polyester sheet was placed around the aortic wall to achieve hemostasis. With careful use of immunosuppressive drugs, renal transplant rejection was avoided. We performed operations safely in all 6 patients. Patients undergoing CABG after successful renal transplantation had a good survival rate. In our research, the cure rate was 100%. We generally preferred mechanical heart valves over bioprosthetic valves because of the young age of the patients. Serum creatinine in renal transplant recipients showed normal level postoperatively. We saw no rejection episodes in our patients postoperatively. Obviously, the risk of rejection is not enhanced when immunosuppressive therapy is maintained throughout the perioperative period.5 Cardiac surgical operation has many risk factors for sepsis, including major tissue trauma, prolonged exposure to air, and physiologic aberrations induced by the mechanical circulatory assist system. Despite all of these risk factors and immunosuppressive therapy, the incidence of wound infection or septicemia was comparable with that in patients not having transplantation. Our study showed that renal transplant recipients can cope with the stress of cardiac surgical operation. The risk of rejection is efficiently controlled by continuing the immunosuppression protocol. This research provides important insights into the immunosuppressive management of a patient requiring cardiac surgery after renal transplantation during the perioperative period. Cardiac operations in renal transplant recipients are effective and safe. Function of the transplanted organ can be maintained at the preoperative level. Acknowledgement: The authors would like to thank Dr. Men Xu and Dr. Sun Lizhong for giving generous support and patient information.