Open heart surgery after renal transplantation

Introduction

In 1975, Lamberti and colleagues ¹ reported the first case of coronary artery bypass grafting (CABG) after renal transplantation. In the same year, Nakhjvan and colleagues ² 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 colleagues ⁶ 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.

Patients and methods

We reviewed 6 open heart operations in 5 patients after renal transplantation among a total of 2340 open heart surgeries (6/2340 = 0.3%) performed between January 1992 and December 2012. The patient characteristics are shown in Table 1. There were 3 men and 2 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.

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Table 1.

Characteristics of 5 patients undergoing cardiac surgery after renal transplantation.

Case no.	Age (years)	Sex	Reason for transplant	Duration of renal graft	Donner	Serum creatine (mg dL−1)	Diagnosis	Open heart surgery	Steroid	Immunosuppressant
1	46	F	CG	10 years	Cadaver	1.65	Old MI + unstable angina	Emergency CABG	Hydrocortisone 500 mg	Cyclosporine 40 mg daily
2	46	F	CG	18 years	Living	2.35	Aortic + mitral stenosis	DVR	Methylprednisolone 1000 mg	Tacrolimus 1.0 mg daily
3	65	M	PK	3 months	Living	1.49	LA myxoma	Myxoma resection	None	Tacrolimus 1.0 mg daily
4	65	M	CG	6 years	Cadaver	3.91	Aortic stenosis	Emergency AVR	Methylprednisolone 1000 mg	None
5A	68	M	CG	3 years	Cadaver	3.17	NVE	Emergency AVR	Hydrocortisone 100 mg	Cyclosporine 30 mg daily
5B	68	M	CG	3.5 years	Cadaver	3.95	PVE	Emergency DVR	Methylprednisolone 1000 mg	Cyclosporine 100 mg orally

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 2.1 ± 0.5 mg dL⁻¹). 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 dL⁻¹) so that intraoperative and postoperative hemodialysis was required. Although DVR ultimately treated his PVE, he died of pneumonia on postoperative day 45. OPEN IN VIEWER

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).

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Table 2.

Open heart surgery after renal transplantation in Japan.

Author	Year	Age (years)	Sex	Reason for RT	Duration of RT	Donor	Diagnosis	Open heart surgery	Steroid	Immunosuppressant	Outcome
Yamamura 5 *	1993	46	F	CG	10 years	Cadaver	Old MI/unstable  angina	Emergency CABG	IV hydrocortisone  500 mg	IV cyclosporine 40 mg day−1	Discharged POD 46
Ando 6	1993	53	F	Unknown	7 years	Living	Unstable Angina	Emergency CABG	None	None	Unknown
Ando 6	1993	48	M	PK	3 years	Living	Effort angina	CABG	None	PO cyclosporine 100 mg	Discharged POD 30
Matsumiya7,8	1994	62	M	Unknown	1.8 years	Living	AR	AVR	IV methylprednisolone  500 mg	IV cyclosporine 100 mg day−1	Alive after 5 years
Mutsumura 9	1997	13	F	PK	5 years	Living	MS + PH	MVR	None	IV cyclosporine 30 mg day−1	Discharged POD 22
Kobayashi 7	1998	47	F	Unknown	2 years	Living	Unstable Angina	Emergency CABG	PO prednisolone 5 mg	None	Alive after 11 months
Kobayashi 7	1998	57	F	Unknown	1 year	Cadaver	AS	AVR	PO prednisolone 10 mg	IV tacrolimus 0.5 mg day−1	Alive after 5 months†
Noda 10	1999	43	M	IgA nephropathy	50 days	Living	subacute MI	CABG	None	IV cyclosporine 2 mg day−1	Discharged POD 15
Noda 10	1999	49	M	Unknown	4 years	Living	Old MI/effort  angina	CABG	None	IV cyclosporine 50 mg day−1	Discharged POD 27
Taketani 11	2000	47	F	Unknown	10 years	Living	Effort angina	CABG	IV methylprednisolone  100 mg	None	Alive after 3 years
Ishigami 12	2000	46	M	CG	5 years	Living	Old MI/effort  angina	Off-pump CABG	Unknown	Unknown	Discharged POD 28
Koyama 13	2000	48	M	Unknown	4.3 years	Living	DAA type A	Emergency modified  Bentall	Unknown	Unknown	Died
Mohri 14	2002	50	M	CG	17 years	Living	AR + MR	DVR	None	PO tacrolimus 1 mg	Discharged POD 27
Sakao 15	2003	65	F	CG	18 years	Living	Effort angina	off-pump CABG	PO prednisolone 5 mg	None	Discharged POD 28
Sakao 15	2003	67	M	CG	2 years	Living	Effort angina	off-pump CABG	PO prednisolone 5 mg	PO tacrolimus 6 mg	Discharged POD 31
Sasahashi 16	2005	35	M	IgA nephropathy	11 years	Living	DAA type A	Emergency aortic  replacement	Methylprednisolone	None	Discharged POD 26
Takahashi 17	2006	58	M	CG	7 years	Unknown	TAA (distal arch)	Distal arch  replacement	IV methylprednisolone  600 mg	None	Discharged POD 25
Hattori 18	2006	59	M	CG	1 year	Living	Unstable angina	Emergency off-pump  CABG	PO prednisolone 4 mg	PO cyclosporine 240 mg	Alive after 1 year
Hayashida 19	2008	56	M	CG	5 years	Cadaver	Silent angina	Off-pump CABG	Hydrocortisone	PO tacrolimus 1.5 mg	Alive after 2 years
Toyama 20	2009	66	M	Nephropathy	2 years	Unknown	TAA (distal arch)	Emergency total  arch graft	Unknown	Unknown	Discharged POD 21
Yanase 21	2011	50	F	SLE	12 years	Living	TAA + post-PCI	TEVAR + off-pump  CABG	Unknown	Unknown	Discharged
Yamamura*	2013	49	F	CG	18 years	Living	AS + MS	DVR	IV methylprednisolone  1000 mg	IV tacrolimus 1.0 mg day−1	Discharged POD 29
Yamamura *	2013	65	M	PK	3 months	Living	LA myxoma	Resection of LA  myxoma	None	IV tacrolimus 1.0 mg day−1	Discharged POD 9
Yamamura*	2013	65	M	CG	6 years	Cadaver	AS	Emergency AVR	IV methylprednisolone  1000 mg	None	Discharged POD 49
Yamamura*	2013	68	M	CG	3 years	Cadaver	NVE	Emergency AVR	IV hydrocortisone  100 mg	IV cyclosporine 30 mg day−1	Discharged POD 45
Yamamura*	2013	68	M	CG	3.5 years	Cadaver	PVE	Emergency DVR	IV methylprednisolone  1000 mg	PO cyclosporine 100 mg	Died POD 45†

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 colleagues ⁴ 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 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 colleagues ⁴ 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 colleagues ²² 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.