Original Article
Open heart surgery after renal transplantation
Asian Cardiovascular & Thoracic Annals 2014, Vol. 22(7) 775–780 ß The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492313507784 aan.sagepub.com
Mitsuhiro Yamamura1, Yuji Miyamoto1, Masataka Mitsuno1, Hiroe Tanaka1, Masaaki Ryomoto1, Shinya Fukui1, Noriko Tsujiya1, Tetsuya Kajiyama1 and Michio Nojima2
Abstract Aim: to evaluate the strategy for open heart surgery after renal transplantation performed in a single institution in Japan. Methods: we reviewed 6 open heart surgeries after renal transplantation in 5 patients, performed between January 1992 and December 2012. The patients were 3 men and 2 women with a mean age of 60 11 years (range 46–68 years). They had old myocardial infarction and unstable angina, aortic and mitral stenosis, left arterial myxoma, aortic stenosis, and native valve endocarditis followed by prosthetic valve endocarditis. Operative procedures included coronary artery bypass grafting, double-valve replacement, resection of left arterial myxoma, 2 aortic valve replacements, and a doublevalve replacement. Renal protection consisted of steroid cover (hydrocortisone 100–500 mg or methylprednisolone 1000 mg) and intravenous immunosuppressant infusion (cyclosporine 30–40 mg day1 or tacrolimus 1.0 mg day1). Results: 5 cases were uneventful and good renal graft function was maintained at discharge (serum creatinine 2.1 0.5 mg dL1). There was one operative death after emergency double-valve replacement for methicillin-resistant Staphylococcus aureus-associated prosthetic valve endocarditis. Although the endocarditis improved after valve replacement, the patient died of postoperative pneumonia on postoperative day 45. Conclusions: careful perioperative management can allow successful open heart surgery after renal transplantation. However, severe complications, especially methicillin-resistant Staphylococcus aureus infection, may cause renal graft loss.
Keywords Coronary artery bypass grafting, Coronary disease, Heart valve diseases, Japan, Kidney transplantation
Introduction
Patients and methods 1
In 1975, Lamberti and colleagues reported the first case of coronary artery bypass grafting (CABG) after renal transplantation. In the same year, Nakhjvan and colleagues2 also reported CABG after renal transplantation. Since these early reports, there have been several studies on open heart surgery after renal transplantation in Western countries.3,4 In Japan, we reported the first case of CABG after renal transplantation in 1993.5 In the same year, Ando and colleagues6 described 2 cases of CABG after renal transplantation. As yet, there has been no analysis of open heart surgery after renal transplantation in Japan. Therefore, the purpose of this study was to evaluate our strategy for open heart surgery after renal transplantations at a single institution in Japan.
We reviewed 6 open heart operations in 5 patients after renal transplantation among a total of 2340 open heart surgeries (6/2340 ¼ 0.3%) performed between January 1992 and December 2012. The patient characteristics are shown in Table 1. There were 3 men and 2 1 Department of Cardiovascular Surgery, Hyogo College of Medicine, Japan 2 Department of Urology & Kidney Transplant Center, Hyogo College of Medicine, Japan
Corresponding author: Mitsuhiro Yamamura, MD, FICA, Department of Cardiovascular Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya-city, Hyogo 663-8501, Japan. Email:
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AVR: aortic valve replacement; CABG: coronary artery bypass grafting; CG: chronic glomerulonephritis; DVR: double-valve replacement; LA: left ventricular; NVE: native valve endocarditis; PK: polycystic kidneys; PVE: prosthetic valve endocarditis.
Cyclosporine 30 mg daily Cyclosporine 100 mg orally Hydrocortisone 100 mg Methylprednisolone 1000 mg 3 years 3.5 years 68 68 5A 5B
M M
CG CG
Cadaver Cadaver
3.17 3.95
NVE PVE
Emergency AVR Emergency DVR
Tacrolimus 1.0 mg daily
None
None
Methylprednisolone 1000 mg Emergency AVR
Myxoma resection LA myxoma
Aortic stenosis 3.91
1.49
6 years
Cadaver
3 months
CG 65 4
M
65 3
M
PK
Living
Cyclosporine 40 mg daily
Tacrolimus 1.0 mg daily Methylprednisolone 1000 mg DVR
Emergency CABG Old MI þ unstable angina
Aortic þ mitral stenosis 2.35
1.65
18 years
Living
10 years
CG F 46 2
F 46 1
Sex
CG
Cadaver
Steroid Open heart surgery Diagnosis Donner
Serum creatine (mg dL1) Duration of renal graft Reason for transplant Age (years) Case no.
Table 1. Characteristics of 5 patients undergoing cardiac surgery after renal transplantation.
Hydrocortisone 500 mg
Asian Cardiovascular & Thoracic Annals 22(7)
Immunosuppressant
776
Figure 1. Changes in renal function (serum creatinine) after open heart surgery.
women with a mean age of 60 11 years (range 46–68 years). The reasons for renal transplantation were chronic glomerulonephritis in 4 patients and polycystic kidneys in one. The mean duration from renal transplantation to open heart surgery was 6 years and 2 months (range 3 months to 18 years). Renal transplantation was performed using cadaver donors in 3 cases and living donors in 2. Open heart surgery was performed for old myocardial infarction and unstable angina, aortic and mitral stenosis, left arterial myxoma, aortic stenosis, and native valve endocarditis caused by Klebsiella pneumoniae followed by methicillin-resistant Staphylococcus aureus (MRSA)-associated prosthetic valve endocarditis (PVE). Operative procedures included CABG, double-valve replacement (DVR), resection of left arterial myxoma, aortic valve replacement in 2 patients, and DVR by the Manouguian’s method. Four procedures were emergency and 2 were elective. Steroid cover during the operations consisted of hydrocortisone 100–500 mg or methylprednisolone 1000 mg, if necessary. Continuous intravenous immunosuppressant infusion was also performed with cyclosporine or tacrolimus. Regarding the intravenous dose of cyclosporine during open heart surgery, we previously reported that 30–40 mg per day (1/3rd of the preoperative oral dose) is enough for open heart surgery after renal transplantation, based on the intraoperative concentrations.5 Regarding the intravenous dose of tacrolimus during open heart surgery, we administrated 1.0 mg per day (1/5–1/2 of the oral dosage) based on a previous report.7
Results Five operative procedures were uneventful and the patients were discharged after 37 15 days (range 9–49 days). The changes in serum creatinine levels after open heart surgery are shown in Figure 1. Renal function at discharge was satisfactory without increased serum creatinine levels (2.4 1.1 to
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2000 47
2000 46
2000 48
2002 50
2003 65
2003 67 2005 35
2006 58
2006 59
2008 56
2009 66
2011 50
2013 49
2013 65
Ishigami12
Koyama13
Mohri14
Sakao15
Sakao15 Sasahashi16
Takahashi17
Hattori18
Hayashida19
Toyama20
Yanase21
Yamamura*
Yamamura *
1999 43 1999 49
1998 57
1998 47
Taketani11
Noda Noda10
10
Kobayashi7
Kobayashi
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M
F
F
M
M
M
M
M M
F
M
M
M
F
M M
F
F
F
Mutsumura9
1997 13
M
Matsumiya7,8 1994 62
7
F M
1993 53 1993 48
Ando6 Ando6
F
PK
CG
SLE
Nephropathy
CG
CG
CG
CG IgA nephropathy
CG
CG
Unknown
CG
Unknown
IgA nephropathy Unknown
Unknown
Unknown
PK
Unknown
Unknown PK
CG
Age Reason (years) Sex for RT
1993 46
5
Year
Yamamura *
Author
Donor
Living
Living
Effort angina DAA type A
Effort angina
AR þ MR
DAA type A
Old MI/effort angina
Effort angina
subacute MI Old MI/effort angina
AS
Unstable Angina
MS þ PH
AR
Unstable Angina Effort angina
Old MI/unstable angina
Diagnosis
off-pump CABG Emergency aortic replacement
off-pump CABG
DVR
Emergency modified Bentall
Off-pump CABG
CABG
CABG CABG
AVR
Emergency CABG
MVR
AVR
Emergency CABG CABG
Emergency CABG
Open heart surgery
Silent angina
Unstable angina
Off-pump CABG
3 months Living
18 years Living
12 years Living
LA myxoma
AS þ MS
TAA þ post-PCI
Resection of LA myxoma
TEVAR þ off-pump CABG DVR
1
IV methylprednisolone 600 mg
PO prednisolone 5 mg Methylprednisolone
PO prednisolone 5 mg
None
Unknown
Unknown
IV methylprednisolone 100 mg
None None
None
IV methylprednisolone 1000 mg
Unknown
Unknown
Hydrocortisone
Unknown Discharged POD 30
Discharged POD 46
Outcome
None
IV cyclosporine 30 mg day1
Discharged POD 29 Discharged POD 9
IV tacrolimus 1.0 mg day1 IV tacrolimus 1.0 mg day1
(continued)
Discharged
Discharged POD 21
Alive after 2 years
Alive after 1 year
Discharged POD 25
Discharged POD 31 Discharged POD 26
Discharged POD 28
Discharged POD 27
Died
Discharged POD 28
Alive after 3 years
Discharged POD 15 Discharged POD 27
Alive after 5 monthsy
Unknown
Unknown
PO tacrolimus 1.5 mg
PO cyclosporine 240 mg
None
PO tacrolimus 6 mg None
None
PO tacrolimus 1 mg
Unknown
Unknown
None
IV cyclosporine 2 mg day IV cyclosporine 50 mg day1
1
Alive after 11 months
Discharged POD 22
IV cyclosporine 100 mg day1 Alive after 5 years
None PO cyclosporine 100 mg
IV cyclosporine 40 mg day
Immunosuppressant
PO prednisolone 10 mg IV tacrolimus 0.5 mg day1
PO prednisolone 5 mg
None
IV methylprednisolone 500 mg
None None
IV hydrocortisone 500 mg
Steroid
Emergency off-pump PO prednisolone 4 mg CABG
2 years Unknown TAA (distal arch) Emergency total arch graft
5 years Cadaver
1 year Living
7 years Unknown TAA (distal arch) Distal arch replacement
2 years Living 11 years Living
18 years Living
17 years Living
4.3 years
5 years Living
10 years Living
50 days Living 4 years Living
1 year Cadaver
2 years Living
5 years Living
1.8 years
7 years Living 3 years Living
10 years Cadaver
Duration of RT
Table 2. Open heart surgery after renal transplantation in Japan.
Yamamura et al. 777
*Case described in this report. yRenal graft loss due to methicillin-resistant Staphylococcus aureus. AR: aortic regurgitation; AVR: aortic valve replacement; CABG: coronary artery bypass grafting; CG: chronic glomerulonephritis; DAA: dissecting aortic aneurysm; DVR: double-valve replacement; IgA: immunoglobulin A; IV: intravenous; LA: left atrial; NVE: native valve endocarditis; PCI: percutaneous coronary intervention; PH: pulmonary hypertension; PK: polycystic kidneys; PO: per os; POD: postoperative day; PVE: prosthetic valve endocarditis; MI: myocardial infarction; MR: mitral regurgitation; MS: mitral stenosis; MRSA: methicillin-resistant Staphylococcus aureus; RT: renal transplantation; SLE: systemic lupus erythematosus; TAA: thoracic aortic aneurysm; TEVAR: thoracic endovascular aortic repair.
Died POD 45y PO cyclosporine 100 mg 2013 68 Yamamura*
M
CG
3.5 years
Cadaver
PVE
Emergency DVR
Discharged POD 45 IV cyclosporine 30 mg day1
IV hydrocortisone 100 mg IV methylprednisolone 1000 mg 2013 68 Yamamura*
M
CG
3 years Cadaver
NVE
Emergency AVR
Discharged POD 49 None IV methylprednisolone 1000 mg Emergency AVR AS 6 years Cadaver CG M 2013 65 Yamamura*
Age Reason (years) Sex for RT Year Author
Table 2. Continued
Duration of RT
Donor
Diagnosis
Open heart surgery
Outcome Immunosuppressant
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Steroid
778
2.1 0.5 mg dL1). There was one operative death (17%) after emergency DVR for MRSA-associated PVE (case 5B in Table 1). This patient initially underwent emergency aortic valve replacement for native valve endocarditis caused by Klebsiella pneumoniae infection, and was discharged (case 5A in Table 1), but 6 months later, he developed MRSA-associated PVE and was treated with vancomycin. Since his MRSA infection had spread to the mitral valve, he underwent emergency DVR by the Manouguian’s method. Because of the administration of vancomycin, his preoperative renal function deteriorated (serum creatinine 3.95 mg dL1) so that intraoperative and postoperative hemodialysis was required. Although DVR ultimately treated his PVE, he died of pneumonia on postoperative day 45.
Discussion Table 2 lists the characteristics and results of 26 open heart operations after renal transplantation in Japan. There were 20 men and 6 women with a mean age of 54 12 years (range 13–68 years). The most common reason for renal transplantation was chronic glomerulonephritis (46%). The mean duration from renal transplantation to open heart surgery was 6 years and 1 month (range 50 days to 18 years). Renal transplantation before open heart surgery was performed using a living donor in 18 patients (69%), a cadaver donor in 6 (23%), and an unknown donor in 2 (8%). Operative procedures included CABG in 13 patients (50%), valve replacement in 8 (31%), and vascular surgery in 5 (19%). Since 2000, off-pump CABG has been performed in an increasing number of patients. There have been 2 cases of renal graft loss following MRSA infection (8%; cases 7 and 26), although the operative mortality rate is good (8%; cases 12 and 26). The number of open heart surgery after renal transplantation in Japan is small (only 6 in our institute and 26 in total in Japan). In contrast, Zhang and colleagues4 recently reported the operative results of open heart surgery after renal transplantation in 57 patients in Washington Hospital Center, USA. The population of renal transplantation patients in Japan is much smaller than that of Western countries. In 2010, 16,899 renal transplantations were performed using cadaver donors in 10,622 (63%) patients and living donors in 6277 (37%) in the USA (2010 database of United Network for Organ Sharing, http://www.unos. org). In the same period in Japan, only 1476 renal transplantations were performed using cadaver donors in 186 (13%) patients and living donors in 1276 (86%; 2010 database of Japan Organ Transplant Network, http://www.jotnw.or.jp). Therefore, the
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renal transplantation population in Japan is 1/10th of that in the USA, and the renal transplantation population receiving cadaver donors in Japan is only 1/50th of that in the USA. Prevention of postoperative infection is very important after open heart surgery in renal transplantation patients. Zhang and colleagues4 reported that 8 (14%) renal grafts were lost and 10 (18%) postoperative infections occurred. Establishing the minimum effective dose of immunosuppressant infusion is the key to the success of open heart surgery after renal transplantation. In 1970, cyclosporine was extracted from a Norwegian fungus (Tolypocladium inflatum Gams), and is now the most widely used immunosuppressant. Cyclosporine is more frequently administered intravenously than orally (6:3 in Table 2), presumably because of its poor oral absorbability. Regarding the intravenous dose of cyclosporine during open heart surgery, Eide and colleagues22 used half of the preoperative oral dose, whereas we used 1/3rd of the preoperative oral dose, based on our previous report,5 and the results were satisfactory. In 1984, tacrolimus was isolated from the Japanese fungus Streptomyces tsukubaensis, and it is now also widely used as an immunosuppressant. Tacrolimus was first used for open heart surgery in 1998.7 Tacrolimus was administrated intravenously and orally in an equal number of patients (Table 2). We used an intravenous dose of tacrolimus based on a previous report.7 Japanese cardiovascular surgeons were not familiar with the use of these intravenous immunosuppressant infusions before heart transplantation started in Japan in 1999.23 This might be another reason why the number of open heart operations after renal transplantation in Japan is so small. In conclusion, we think that careful perioperative management can allow successful open heart surgery after renal transplantation. However, severe complications, especially MRSA infection, may cause renal graft loss.
Acknowledgements We thank Yuki Imamura, RN and Ryoko Yagi (Fujiwara), RN (Transplant Coordinator, Japan Organ Transplant Network) for their assistance. Presented at the 20th Annual Meeting of Asian Society for Cardiovascular & Thoracic Surgery, Indonesia, March 2012.
Funding This research received no specific grant from any funding agency in the public, commerical, or not-for-profit sectors.
Conflict of interest statement None declared
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