HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Giuseppe Bruschi Tiziano Colombo Andrea Garatti Ettore Vitali Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bruschi, G. Articles by Vitali, E. Search for Related Content PubMed PubMed Citation Articles by Bruschi, G. Articles by Vitali, E. Related Collections Transplantation - heart

Ann Thorac Surg 2007;84:522-527
© 2007 The Society of Thoracic Surgeons

---

Original Articles: Cardiovascular

Long-Term Follow-Up of Simultaneous Heart and Kidney Transplantation With Single Donor Allografts: Report of Nine Cases

^a Department of Cardiology and Cardiac Surgery "A. De Gasperis,", Niguarda Ca’ Granda Hospital, Milan, Italy
^b Nephrology Unit, Niguarda Ca’ Granda Hospital, Milan, Italy
^c Kidney-Pancreas Transplantation Unit, Niguarda Ca’ Granda Hospital, Milan, Italy

Accepted for publication April 2, 2007.

^_* Address correspondence to Dr Bruschi, "A De Gasperis" Cardiology and Cardiac Surgery Department, Niguarda Ca’ Granda Hospital, Piazza Ospedale Maggiore, 3, Milan, 20162, Italy (Email: giuseppe.bruschi{at}fastwebnet.it).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment References

 
Background: Combined heart-kidney transplantation is an accepted therapeutic option for patients with end-stage heart disease associated with severely impaired renal function. We report our single-institutional experience with this combined procedure and long-term follow-up.

Methods: Between April 1989 and August 2006, 9 patients underwent combined simultaneous heart-kidney transplantation at our center. Seven patients were male (mean age, 45.2 ± 10.12 years); 7 patients were on dialysis at transplantation. Whenever possible, donors were selected on the basis of ABO identity, weight (ratio 0.9), on-site or short-distance procurement, young age, low inotropic support, and normal renal function.

Results: Mean ischemic time was 132.2 ± 57.0 minutes for the cardiac allograft and 6.0 ± 1.0 hours for the kidney. Surgical procedure was uneventful in all patients. One patient died in the intensive care unit 41 days after transplantation. Three patients died during follow-up, 1 of lung neoplasm after 6 years, 1 of cerebral stroke after 34 months, and 1 of infection and multiorgan failure after 148 months. The mortality rates led to an overall actuarial survival of 88.9% ± 10.4% at 1 year, 77.8% ± 13.6% at 5 years, and 64.8% ± 16.5% at 10 years. Seven patients lived beyond 5 years, 4 beyond 10 years, and the patient who has longest survival is patient no. 1, with 17 years of follow-up. One patient lost kidney function after 113 months.

Conclusions: In selected patients, with coexisting end-stage cardiac and renal failure, combined heart-kidney transplantation with allograft from the same donor proved to have satisfactory short- and long-term results, with a low incidence of both cardiac and renal allograft rejection.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment References

 
Norman and associates [1] described in 1978 the first combined simultaneous heart and kidney transplant (HKTx) in a patient maintained on an left ventricular assist device for 5 days before transplant. The patient died 15 days after transplant of gram-negative sepsis, with no evidence of cardiac or renal allograft rejection. The first successful HKTx with long-term survival was performed in 1986: during the first 3 months after transplant, five episodes of cardiac rejection were documented, but no episodes of renal graft rejection had occurred [2]. Since then, the number of simultaneous HKTx increased every year, and the Registry of the International Society for Heart and Lung Transplantation (ISHLT) has recorded so far more than 350 such procedures [3]. Combined heart-kidney transplantation has so become an accepted therapeutic option for patients with end-stage heart disease associated with severely impaired renal function.

We report our single-institutional experience with combined HKTx transplantation with follow-up extending beyond 10 years.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment References

 
This study was approved by the Local Ethics Committee with a waiver to obtain consent based on the retrospective study nature and removal of identification of patient data.

Between January 1972 and December 2006, 1,676 kidney transplantations (KTx) were performed at our Hospital, 1,445 first kidney, 154 second and third kidneys, and 77 simultaneous double transplantations (kidney and pancreas, kidney and liver, kidney and heart). Heart transplantation (HTx) started in our center on November 1985, and as of December 2006, 786 patients have been transplanted. Since April 1989, 9 of the 720 adult heart transplanted patients (1.2%) received a simultaneous heart and kidney transplantation. These patients, affected by cardiomyopathy, had severe renal failure for primary kidney disease when already listed for heart transplantation or were on chronic hemodialysis when a cardiomyopathy developed and they consequently were excluded for kidney transplantation alone. Combined heart and kidney transplantation were performed with allografts harvested from the same donor.

All patients signed an informed consent. Seven patients were male (77.7%). Mean age at transplant was 45.2 ± 10.12 years (range, 24 to 55). The etiology of end-stage heart failure was idiopathic cardiomyopathy in 3 patients (33.3%) and ischemic cardiomyopathy in 5 (55.5%). Each patient had severe fixed impairment of systolic cardiac function with an average left ventricle ejection fraction of 20%, a mean cardiac index of 2.3 ± 0.5, and New York Heart Association class III or IV symptoms. In 4 patients (44.4%), a previous cardiac surgery was recorded. Renal failure was secondary to interstitial nephritis in 3 patients, kidney vascular disease in 2, glomerular disease in 1, and eredofamilial in 2. Seven patients (77.7%) had irreversible end-stage renal failure managed by dialysis for a period ranging from 8 to 396 weeks; the creatinine clearance of the other 2 patients was 17 and 21 mL/min. Patient characteristics are summarized in Table 1.

Heart and kidney harvesting, preservation, and grafting were performed according to the routine technique and previously described [4]. Orthotopic heart transplantation was performed first in all cases. After hemodynamic stability and hemostasis were achieved, the chest was closed, and kidney transplantation was then performed without delay in standard fashion.

Patients were given perioperative cefazolin or vancomycin and gentamycin in the case of a penicillin allergy.

The overall immunosuppressive protocol was the same as for heart or kidney transplantation alone: it consisted of triple therapy with steroids, azathioprine, and cyclosporine. Induction immunosuppression was obtained using rabbit anti-thymocyte globulins (ATG-Fresenius, Bad Homburg, Germany) 2.5 mg/kg intraoperatively and 1 to 2 mg/kg daily for 4 days. Methylprednisolone was administered during surgery (500 mg) and then 250 mg intravenously every 12 hours for 3 doses postoperatively; followed by prednisone 0.8 mg/kg daily and progressively tapered to 0.2 mg/kg daily within the 11th postoperative day. Azathioprine was administered intravenously at time of surgery (3 mg/kg) and maintained at 1.5 mg/kg daily postoperatively according to peripheral leukocytes count. Cyclosporine was started soon after surgery (6 to 12 hours after HKTx) and gradually increased to obtain trough whole blood levels of 350 to 450 ng/mL.

Early and late surveillance of cardiac rejection was performed by endomyocardial biopsies starting on day 7, then weekly for 4 weeks, twice monthly for 3 months, monthly until 6 months, and then every 2 months until 1 year. Patients underwent endomyocardial biopsy every 3 months until year 2, and then they had an endomyocardial biopsy once or twice yearly or in cases of suspected graft rejection. Routine renal biopsies were not foreseen unless resistant rejection occurred: they were never performed in this group of patients. Early surveillance of kidney rejection was obtained by daily monitoring creatinine serum levels and by noninvasive means as renal ultrasonography. Abdominal computed tomography was used only when a surgical complication was suspected.

	Results

Top Abstract Introduction Patients and Methods Results Comment References

 
Seven donors were male; ages ranged from 18 to 69 years (mean, 29.3 ± 16.2). Donors and immunologic profiles are summarized on Table 2.

Patient no. 9 did not recover autonomous renal function after HKTx, and underwent regular dialysis treatment after surgery. She later had systemic multiorgan failure and died 41 days after HKTx.

Cross matches were negative in all cases. The rejection profiles, clinical results, and outcomes are summarized in Table 3.

The cardiac follow-up has been complicated by arterial hypertension, which required an increase in hypotensive therapy in 7 patients, and coronary allograft vasculopathy in 2 patients. Patient 1 had type A and B coronary artery disease, and patient 6 had a subcritical focal lesion of the anterior descending artery. The cardiac function remained normal in long-term surviving patients; last visit mean ejection fraction, measured by echocardiography, for these patients has been 59% ± 6%; all patients are New York Heart Association class I or II. In 2 patients, insulin-dependent diabetes mellitus developed. Renal allograft complications have been chronic renal failure secondary to hypertension, or cyclosporine nephrotoxicity, or both in 1 patient. Four of the 5 surviving patients in September 2006 have functioning kidney allografts; the mean glomerular filtration rate in the surviving patients was 65 ± 15 mL/min at the last follow-up outpatient visit.

Patient no. 9 died in the intensive care unit 41 days after HKTx, so in-hospital mortality in our series was 11.1%. Among discharged patients, patient 3 died of infection and multiorgan failure 148 months after HKTx, patient 5 died of lung neoplasm after 6 years, and patient 7 died of cerebral stroke 34 months after transplantation. The mortality rates led to an overall actuarial survival 88.9% ± 10.4% at 1 year and 77.8% ± 13.6% and 64.8 ± 16.5% at 5 and 10 years, respectively (Fig 1). This results are comparable with our survival in HTx patients, that is, 87.0% ± 1.3%, 78.1% ± 1.6%, and 63.0% ± 2.1% at 1, 5, and 10 years, respectively.

View larger version (21K): [in this window] [in a new window]   Fig 1. Actuarial survival of heart transplant alone (HTx [solid line]) and heart and kidney transplant (HKTx [dashed line]) patients.

	Comment

Top Abstract Introduction Patients and Methods Results Comment References

 
Although combined heart-kidney transplantation with allografts from the same donor has been long proved to be a feasible therapeutic option [4, 5], it is rarely performed. The Registry of the International Society for Heart and Lung Transplantation has so far recorded 350 such procedures on more than 73,000 heart transplants [3].

The United Network for Organ Sharing Registry (UNOS) reports 429 such combined organ transplantations performed between 1987 and 2006. During the same period, 39,603 heart and 224,073 kidney transplantations were performed in the United States, and combined HKTx represents 1.08% and 0.19% of the total heart and kidney transplantation experiences, respectively, during the same period [6].

In our institution, 786 patients underwent heart transplantation, and 1676 kidney transplantations were performed, whereas only 9 such combined procedures have been performed. At present, 1-, 5-, and 10-year survival of 94.6%, 84.8%, and 69.1%, respectively, for discharged patients, can be expected for heart transplantation. The actuarial survival rates of kidney transplanted patients is 94% and graft survival rate is 75% at 5 years. Our results with low hospital mortality and good long-term survival of discharged patients, with a 1-, 5-, and 10-year survival of 100%, 87.5%, and 74.1%, confirm that this procedure is a valuable option for selected patients suffering from concurrent failure of both organs.

As the waiting lists for heart or kidney transplantation continue to increase, the potential for second-organ dysfunction that requires consideration for multiorgan transplantation may occur in larger group of patients. The kidney remains the most vulnerable extrathoracic organ in patients awaiting HTx. Patients with either organic kidney disease or intrinsic renal disease as a consequence of systemic conditions have the added burden of a low cardiac output, which can lead to or potentiate renal dysfunction [7]. However, it is imperative to select the appropriate recipients, otherwise some patients would be "overtreated." It has already been demonstrated that patients who suffer from terminal cardiac insufficiency and are dialysis dependent for at least 3 months due to an intrinsic kidney disease, cannot expect to regain kidney function after successful heart transplantation [8]. However, patients with mainly hemodynamically mediated renal failure and without intrinsic kidney disease—as proved by the lack of proteinuria, normal kidney size at ultrasonography, and the absence of severe histopathology in renal biopsy specimens—can recover their native kidney function after restoration of perfusion; and in that case, an isolated heart transplant alone will be sufficient to restore native renal function [9]. Our cardiac recipient selection criteria have been described previously [10]; for selection for renal transplantation, all the patients described had irreversible organ damage, with 77.7% requiring renal support therapy preoperatively by hemodialysis or continuous ambulatory peritoneal dialysis, for a period ranging from 2 to 99 months.

To prevent renal injury, some authors prefer a staged approach in which kidney transplantation is delayed to a second operative procedure, usually 12 to 16 hours after HTx regardless of donor heart function [11] or until cardiac function has stabilized after cardiopulmonary bypass [12]. This strategy should be used in cases of initial donor heart dysfunction with hemodynamic failure. In this situation, the ischemic kidney graft is exposed to reperfusion under the conditions of hemodynamic instability with low perfusion pressure and high doses of vasoconstrictive drugs, and that may cause delayed renal allograft function. In our series, on the contrary, kidney transplantation was always performed immediately after heart transplantation during the same surgical session. This strategy provided the shortest possible cold ischemic time for the kidney, avoided a second anesthesia, and minimized the logistic efforts and time for the procedure.

The use of hemofiltration during cardiopulmonary bypass in the anuric patients was useful either for the management of the intraoperative fluid balance due to hemodilution, and of hyperkalemia, through repeated administration of potassium-enriched blood cardioplegia for myocardial protection.

In our series, no prospective human leukocyte antigen matching was performed. Although human leukocyte antigen matching has been shown to be advantageous not only for renal, but also for cardiac allograft survival [13], this type of prospective testing was not done, in the effort to minimize heart and kidney cold ischemic time. A longer ischemic time may lead to increased immunogenicity of the renal parenchyma and therefore to poorer renal function, with significantly reduced long-term survival [14]. With the selection of donor and recipient matching based on ABO group identity and low panel-reactive lymphocytotoxic antibodies and with the relatively short donor ischemic times, the early and long-term rejection profiles of the simultaneous HKTx recipients in our report have been excellent.

Different mechanisms may be responsible for this immunologic course. The immunosuppressive regimen used was the standardized protocol employed for single HTx or KTx in our hospital, consisting of an induction therapy added to standard triple immunosuppression therapy. For maintenance drugs, the target doses and cyclosporine levels as defined by protocol are generally higher for HTx and HKTx than for KTx alone. According to other authors [15], the use of rabbit anti-thymocyte globulins was effective in preventing early and late rejection and allowed a safe perioperative management of cyclosporine therapy. We also believe that surveillance endomyocardial biopsy, pathologic documentation of heart rejection, careful follow-up, and accurate cyclosporine dosage monitoring have been important elements in our medical follow-up strategy.

It has long been observed in experimental animals studies that multiple transplanted organs from the same donor protect each other immunologically. It is recognized that combining transplantation of two organs might reduce the risk of acute rejection of each of them: simultaneous pancreas and kidney transplantation results in higher pancreas survival than if the pancreas is transplanted alone [16]; and in heart-lung transplant recipients, cardiac rejection is less common than pulmonary rejection, and pulmonary grafts respond more rapidly to antirejection therapy than isolated cardiac grafts [17]. This observation suggests that any organ transplant combination may facilitate graft tolerance or reduce host immunoresponsiveness.

Local donors should be preferred whenever possible to minimize ischemic damage, but most of all, young age and donor conditions have to be looked after. In our experience, the recipient who received the organs from an aged donor had a primary kidney nonfunction. This generated a sequel of events that resulted in medical complications and ultimately led to the patient’s death in the intensive care unit.

The complications of long-term immunosuppression therapy are well documented. Hypertension is common in HTx patients and in cyclosporine-treated renal allografts as well, so we generally treat our patients with calcium-channel blockers and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers to preserve long-term renal function and to provide potential long-term protection from coronary vasculopathy [18].

Given the good results of combined HKTx reported in literature and on the ISHT and UNOS Registries, the indications for transplantation in patients with coexisting end-stage heart and kidney disease have been expanded. Our report confirmed excellent long-term results and actuarial survival of this procedure and emphasized that simultaneous HKTx is an effective therapeutic option for a growing number of patients. Indications include potential candidates for renal transplantation who developed a coexisting end-stage heart disease, with no indication for other cardiac operative interventions and heart transplant candidates with severe chronic renal dysfunction caused by a fixed and nonreversible parenchymal disease but no other significant comorbidity. Intermediate and long-term results are similar to those of single-organ transplantation, with a low incidence of rejection when HKTx is performed with allografts from the same donor, and kidney transplantation is performed immediately after the heart transplantation procedure.

Medical controversy exists about this combined approach in that it may not represent a rational or optimal use of scarce donor resources: two organs are allocated to a single patient with double organ failure rather than transplanting two different patients with single organ failure. We believe that our results demonstrate that a careful screening of potential recipients, necessary to identify those most likely to obtain a long-term benefit, and a careful selection of donors made this approach a rational utilization of resources.

	References

Top Abstract Introduction Patients and Methods Results Comment References

 

1. Norman J, Cooley D, Kahan B, et al. Total support of the circulation of a patient with post-cardiotomy stone-heart syndrome by a partial artificial heart (ALVAD) for 5 days followed by heart and kidney transplantation Lancet 1978;1:1125-1127.[Medline]
2. Livesey S, Rolles K, Calne R, Wallwork J, English TAH. Successful simultaneous heart and kidney transplantation using the same donor Clin Transplant 1988;2:1-4.[Medline]
3. Taylor DO, Edwards LB, Boucek MM, et al. The Registry of the International Society for Heart and Lung Transplantation: twenty-third official adult heart transplantation report 2006 J Heart Lung Transplant 2006;25:869-879.[Medline]
4. Colucci V, Quaini E, Magnani P, et al. Combined heart and kidney transplantation: an effective therapeutic option—report of six cases Eur J Cardiothorac Surg 1997;12:654-658.[Abstract/Free Full Text]
5. Gonwa TA, Nery JR, Husberg BS, Klintmalm GB. Simultaneous liver and renal transplantation in man Transplantation 1988;49:690-693.
6. Savdie E, Keogh AM, Macdonald PS, et al. Simultaneous transplantation of the heart and kidney Aust NZ J Med 1994;24:554-560.[Medline]
7. U.S. Department of Health and Human Services. 2005 annual report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: transplant data 1995–2004. Rockville, MD: Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation (available at: www.unos.org).
8. Vossler MR, Hanyu N, Toy W, Hersrhberger RE. Pre-operative renal function predicts development of chronic renal insufficiency after orthotopic heart transplantation J Heart Lung Transplant 2002;21:874-881.[Medline]
9. Bergler-Klein J, Pirich C, Laufer G, et al. The long-term effects of simultaneous heart and kidney transplantation on native renal function Transplantation 2001;71:1597-1600.[Medline]
10. Frigerio M, Gronda EG, Mangiavacchi M, et al. Restrictive criteria for heart transplantation candidacy maximize survival of patients with advanced heart failure J Heart Lung Transplant 1997;16:160-168.[Medline]
11. Blanche C, Valenza M, Czer LS, et al. Combined heart and kidney transplantation with allografts from the same donor Ann Thorac Surg 1994;58:1135.[Abstract/Free Full Text]
12. Gonwa TA, Husberg BS, Klintmalm GB, et al. Simultaneous heart and kidney transplantation: a report of three cases and review of the literature J Heart Lung Transplant 1992;11:152.[Medline]
13. Opelz G, Wujciak T. Influence of HLA compatibility on graft survival after heart transplantation N Engl J Med 1994;330:816-819.[Medline]
14. Kocher AA, Schlechta B, Kopp CW, et al. Combined heart and kidney transplantation using a single donor Transplantation 1998;66:1760-1763.[Medline]
15. Zerbe TR, Arena VC, Kormos RL, Griffith BP, Hardesty RL, Duquesnoy RJ. Histocompatibility and other risk factors for histological rejection of human cardiac allografts during the first three months following transplantation Transplantation 1991;52:485-490.[Medline]
16. Sutherland DER, Chow SY, Moudry-Munns KC. International Pancreas Transplant Registry report Clin Transpl 1989;3:129-149.[Medline]
17. Wahlers T, Khaghani A, Martin B, Banner N, Yacoub M. Frequency of acute heart and lung rejection after heart-lung transplantation Transplant Proc 1987;18:3537-3538.
18. Trachiotis GD, Vega JD, Johnston TS, et al. Ten-year follow-up in patients with combined heart and kidney transplantation J Thorac Cardiovasc Surg 2003;126:2065-2071.[Abstract/Free Full Text]

This article has been cited by other articles:

				R.-B. Hsu, C.-I. Chang, M.-K. Tsai, P.-H. Lee, N.-K. Chou, N.-H. Chi, S.-S. Wang, and S.-H. Chu Effect of simultaneous kidney transplantation on heart-transplantation outcome in recipients with preoperative renal dysfunction Eur J Cardiothorac Surg, January 1, 2010; 37(1): 68 - 73. [Abstract] [Full Text] [PDF]

				D. E. Jaroszewski, C. C. Pierce, L. L. Staley, R. Wong, R. R. Scott, E. E. Steidley, R. S. Gopalan, P. DeValeria, L. Lanza, D. Mulligan, et al. Simultaneous Heart and Kidney Transplantation After Bridging With The CardioWest Total Artificial Heart Ann. Thorac. Surg., October 1, 2009; 88(4): 1324 - 1326. [Abstract] [Full Text] [PDF]

				R.-B. Hsu, M.-K. Tsai, P.-H. Lee, C.-M. Lee, M.-F. Chen, S.-S. Wang, F.-Y. Lin, and S.-H. Chu Simultaneous heart and kidney transplantation from a single donor Eur J Cardiothorac Surg, December 1, 2008; 34(6): 1179 - 1184. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Giuseppe Bruschi Tiziano Colombo Andrea Garatti Ettore Vitali Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bruschi, G. Articles by Vitali, E. Search for Related Content PubMed PubMed Citation Articles by Bruschi, G. Articles by Vitali, E. Related Collections Transplantation - heart