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: [email protected]

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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

Asian Cardiovascular & Thoracic Annals 22(7)

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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Open heart surgery after renal transplantation.

to evaluate the strategy for open heart surgery after renal transplantation performed in a single institution in Japan...
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