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Keywords:

  • Combined transplants;
  • heart transplantation;
  • kidney transplantation;
  • liver transplantation;
  • lung transplantation

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. References

Simultaneous thoracic and abdominal (STA) transplantation is controversial because two organs are allocated to a single individual. We studied wait-list urgency, and whether transplantation led to successful outcomes. Candidates and recipients for heart–kidney (SHK), heart–liver (SHLi), lung–liver (SLuLi) and lung–kidney (SLuK) were identified through the United Network for Organ Sharing (UNOS) and outcomes were compared to single-organ transplantation. Since 1987, there were 1801 STA candidates and 836 recipients. Wait-list survival at 1- and 3 years for SHK (67.4%, 40.8%; N = 1420), SHLi (65.7%, 43.6%; N = 218) and SLuLi (65.7%, 41.0%; N = 122), was lower than controls (p < 0.001), whereas for SLuK (65.0%, 51.6%; N = 41) it was comparable (p = 0.34). All STA groups demonstrated similar 1- and 5 years posttransplant survival to thoracic controls. Compared to abdominal controls, 1- and 5 years posttransplant survival in SHK (85.3%, 74.0%; N = 684), SLuLi (75.5%, 59.0%; N = 42) and SLuK (66.7%, 55.6%; N = 18) was decreased (p < 0.01), but SHLi (85.9%, 74.3%; N = 92) was comparable (p = 0.81). In summary, STA candidates had greater risk of wait-list mortality compared to single-organ candidates. STA outcomes were similar to thoracic transplantation; however, outcomes were similar to abdominal transplantation for SHLi only. Although select patients benefit from STA, risk-exposure variables for decreased survival should be identified, aiming to eliminate futile transplantation.


Abbreviations
ISHLT

International Society for Heart and Lung Transplantation

MELD

model for end-stage liver disease

SHK

simultaneous heart–kidney

SHLi

simultaneous heart–liver

SLuK

simultaneous lung–kidney

SLuLi

simultaneous lung–liver

STA

simultaneous thoracic and abdominal transplantation

UNOS

United Network for Sharing.

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. References

Simultaneous thoracic and abdominal transplantation (STA) is a life-saving surgery for a subset of patients with dual-organ failure. Several reports from single centers demonstrate successful posttransplant outcomes, particularly for SHK and SHLi [1-7]. Over the last 5 years, there have been robust increases in the numbers of dual-organ wait-list candidates and STA recipients. As the frequency of STA increases, it poses a challenge to the principles of organ allocation because two life-saving organs are used to benefit one patient instead of two separate individuals [8]. Whether or not distribution of two organs simultaneously to one recipient is justifiable remains relatively unexplored.

The goals of the organ allocation system in the United States, as outlined in 1998 by the Health and Human Services in the ‘Final Rule’, are to prioritize patients with the greatest medical urgency, while at the same time maximizing the overall societal benefit from a limited pool of organs [9]. These underlying principles are included in the American Medical Association's Code of Medical Ethics, which recommends that scarce medical resources, including solid organs, should be allocated based on “likelihood of benefit, urgency of need, change in quality of life, duration of benefit, and, in some cases, the amount of resources required for successful treatment [10].” The Ethics Committee for the United Network for Sharing (UNOS) restated these ideas using the discrete terms: justice and utility. Justice refers to fairness in distribution based on a number of factors (medical urgency, likelihood of finding a suitable organ in the future, waiting time, first vs. repeat transplants and age), whereas utility refers to the greatest aggregate good that can be achieved through distribution of a scarce resource to the whole population [11].

Whether STA is supported by justice and utility is debatable. STA could be considered to follow the principle of justice if candidates have greater medical urgency than non-STA candidates. Medical urgency in this context is distinguished from medical need, in that the former refers to the likelihood of poor outcome if an individual is denied a given resource, and the latter refers to the extent/number of resources required. By definition, STA candidates all have greater medical need than single-organ candidates, but whether or not they have greater medical urgency, as defined by higher waitlist mortality, has not been explored. With respect to utility, STA appears untenable; multiple organs are allocated to a single patient with fewer patients benefiting from the organ pool. However, utility not only considers the total number of beneficiaries, but also the long-term viability of the allocated resource. To support the legitimacy of STA, transplant outcomes that are at least equivalent to single-organ recipients would be expected.

This study explores the legitimacy of STA in accordance with the guiding principles of organ allocation. In the first half, we test the hypothesis that candidates listed for STA have increased wait-list mortality compared to single-organ candidates. The analysis then examines patient survival among the four most common STA subtypes in relation to the survival of single-organ abdominal and thoracic transplant recipients. It is not our intention to consider the breadth of ethical nuances related to STA, but rather, to illuminate STA in the context of the current goals of organ allocation.

Patients and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. References

Study design and patient population

This is a retrospective cohort study using the UNOS database from 1987 through October 2010. Institutional Review Board approval was obtained from the Hospital of the University of Pennsylvania (IRB # 812829).

A total of 1801 STA candidates simultaneously wait-listed for combined thoracic and abdominal organ transplantation were identified in the UNOS thoracic, kidney/pancreas and liver data sets. Our analysis included four dual-organ combinations (SHK = 1420, SHLi = 218, SLuLi = 122, SLuK = 41). Although we identified several other dual (heart–pancreas; N = 5, lung–pancreas; N = 3) and various triple-organ combinations (N = 33), these groupings were excluded due to inadequate number of patients. Among patients with multiple entries in a single data set, only the most recent listing was included, as determined by the wait-list end date. Since a patient listed for a STA may have had slightly different listing and removal dates for each organ, time spent on the thoracic organ wait-list was used to approximate overall STA wait-list time.

Comparison groups comprised of patients wait-listed for a single identical thoracic or abdominal organ (heart-alone = 72 084; lung-alone = 32 393; liver-alone = 163 604; kidney-alone = 441 666). As with STA wait-list cohorts, only the most recent entry was included for those patients with multiple entries.

Eight hundred thirty-six STA recipients (SHK = 684; SHLi = 92; SLuLi = 42; SLuK = 18) who received a thoracic and abdominal organ from the same donor were identified. Comparison groups consisted of all transplant recipients of a single thoracic or single abdominal organ (heart-alone = 47 440; lung-alone = 20 384; liver-alone = 80 332; kidney-alone = 189 038). The first transplant was used as the reference point for control patients who received multiple single-organ transplants. Both single and bilateral lung transplants were included in the controls. Recipients of living donor kidneys and livers, and recipients of small-bowel and multivisceral transplants were excluded from our analyses.

Statistical analysis

Continuous variables were described with measures of central tendency and categorical variables were listed as percentages of the total cohort. Removal from the wait-list for death or deteriorating health conditions were considered mortality events. Removal for all other reasons, including transplantation, were censored. Patient survival was estimated using Kaplan–Meier survival and compared with log-rank testing. Survival time for candidates was measured from the time of listing and events were measured as removal from the list due to death or deteriorating health. Survival benefit of STA was quantified by comparing risk of death following transplant to the risk of death while remaining on the wait-list for both organs. For this analysis, models were created where candidates contributed time to the wait-list, but were censored at time of transplant, and subsequently accrued time in the transplant risk group. To quantify differences in survival between wait-list and transplant groups, Cox regression models were constructed with age, gender and race entered as covariates. The threshold for statistical significance for all testing was set as p < 0.05. Analysis was performed using SPSS Statistics version 19.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. References

STA trends in demand and practice, 1987–2010

Annual numbers of STA wait-list candidates and transplants have increased steadily since 1987, particularly during the last 5 years (Table 1). SHK was the largest overall cohort, with a total of 1420 listed patients, and 684 received an SHK transplant. Between 2006 and 2010, 606 patients were listed for both heart and kidney and 272 received both organs, representing a 52% increase in demand and a 37% increase in transplants over the prior 5-year interval (2001–2005). More than 50 SHK transplants have been performed annually since 2007. SHLi was the second largest STA group with 212 patients listed and 92 transplants performed since 1987. Comparing the last two 5-year intervals (2006–2010 vs. 2001–2005), patients listed for both heart and liver increased from 46 to 118 (+56%) and SHLi transplants from 21 to 51 (+42%). The first SLuLi and SLuK transplants occurred in 1994 and 1995, respectively. These combinations remain relatively uncommon; however, trends were similar to those for SHK and SHLi. A total of 122 SLuLi patients have been wait-listed and 42 transplanted since 1987, with 53 wait-listed and 23 transplanted since 2006. Forty-one SLuK patients have been wait-listed since 1987 (18 since 2006) and 16 of those received transplants (10 since 2006).

Table 1. STA transplantation in the United States (1987–2010)
Date rangeSHKSHLiSLuLiSLuK
ListedTransplantedListedTransplantedListedTransplantedListedTransplanted
  1. Abbreviations: SHK = simultaneous heart–kidney; SHLi = simultaneous heart–liver; SLuLi = simultaneous lung–liver; SLuK = simultaneous lung–kidney.

1987–19902021000000
1991–19951286210411251
1996–2000267131441623783
2001–200539919846213510104
2006–20106062721185153231810
Totals142068421892122424118

Medical urgency for STA wait-list patients: comparisons of wait-list mortality

Etiology of organ failure

Etiologies for organ dysfunction among patients wait-listed for STA are listed in Table 2. For SHK, heart failure was most commonly due to nonischemic cardiomyopathy (N = 576), ischemic cardiomyopathy (N = 519) and retransplantation/graft failure (N = 192), whereas kidney dysfunction was due to diabetes (N = 196), tubular/interstitial disease (N = 165) and glomerulonephritis (N = 159). For those awaiting SHLi, heart failure was attributable to nonischemic (N = 129) and ischemic cardiomyopathy (N = 25), and liver dysfunction to noncholestatic (N = 76) and metabolic (N = 19) diseases. The SLuLi cohort consisted of a majority (N = 70) of patients with cystic fibrosis. The primary causes of pulmonary failure in SLuK patients included restrictive (N = 20) and pulmonary vascular diseases (N = 10).

Table 2. Etiology of organ dysfunction in STA wait list subgroups
nSHKSHLiSLuLiSLuK
142021812241
  1. Abbreviations: SHK = simultaneous heart–kidney; SHLi = simultaneous heart–liver; SLuLi = simultaneous lung–liver; SLuK = simultaneous lung–kidney.

Etiology of end-stage renal disease
Diabetes1962
Tubular and interstitial diseases16510
Glomerulonephritis1595
Hypertensive nephrosclerosis1434
Retransplantation/graft failure752
Polycystic kidney430
Renovascular diseases383
Other/unspecified by UNOS59115
Etiology of end-stage liver disease
Noncholestatic liver disease7629
Metabolic diseases197
Cholestatic liver disease127
Other/unspecified by UNOS11179
Etiology of lung failure
Cystic fibrosis or immunodeficiency disorder706
Pulmonary vascular disease2210
Restrictive lung disease1320
Obstructive lung disease114
Other/unspecified by UNOS61
Etiology of heart failure
Nonischemic cardiomyopathy576129
Ischemic cardiomyopathy51925
Retransplant/graft failure1922
Valvular heart disease333
Other/unspecified by UNOS10059
STA characteristics

The populations awaiting STA had distinct demographic and clinical characteristics compared to patients wait-listed for single-organ transplantation (Table 3). SHLi, SLuLi and SLuK candidates were younger on average than their respective thoracic and abdominal control groups, whereas SHK candidates were older compared to heart-alone (p < 0.001). Listing status for SHK and SLuK candidates was more advanced compared to heart (p < 0.001) or lung alone (p = 0.02), but SHLi candidates were listed at lower heart status (p < 0.001). LAS scores for SLuLi were comparable to those for lung alone (p = 0.22), and MELD scores for both SLuLi and SHLi were lower compared to liver alone (p = 0.06). Compared to kidney alone, wait-list times for SHK and SLuK were significantly reduced (p < 0.001). SHK and SHLi had significantly prolonged wait-list times compared to heart-alone (p < 0.001). In all STA wait-list groups, a lower percentage of patients ultimately received transplants (either single transplant or STA) when compared to thoracic-only candidates (p < 0.001). SLuLi and SLuK candidate groups both also had lower percentages of transplantation compared to abdominal-only candidates (p < 0.001). Of note, a group of 146 patients who were initially waitlisted for SHK eventually received a heart-alone transplant. Posttransplant survival at 1 and 5 years was significantly lower in this population (56.7%, 44.1%) compared to those waitlisted for SHK who received a combined transplant (85.3%, 74.0%) (p < 0.001).

Table 3. Comparison of double and single organ wait-list candidates
nSHKSHLiSLuLiSLuKHeart aloneLung aloneKidney aloneLiver alone
1,4202181224172 08432 393441 666163 604
  • Abbreviations: SHK = simultaneous heart–kidney; SHLi = simultaneous heart–liver; SLuLi = simultaneous lung–liver; SLuK = simultaneous lung–kidney; BMI = body massindex; MELD = model for end-stage liver disease; FVC = forced vital capacity; INR = international normalized ratio.

  • TSignificant difference between STA cohort and the associated thoracic-organ control group.

  • ASignificant difference between STA cohort and the associated abdominal-organ control group.

  • 1

    BMI > 60 excluded, implausible.

  • 2

    Data beginning 5/4/2005.

  • 3

    Data beginning 2/27/2002.

  • 4

    Data through 2007.

  • 5

    Data reported as median (range).

  • 6

    Includes both single and double (STA) transplantation.

  • *

    Chi-squared analysis was performed as a single test with all listed variables; significant test results, if present, are indicated with “T” or “A” in first row only.

Age, years48.7 (13.7)T42.9 (16.3)TA32.3 (15.9)TA39.0 (14.2)TA45.5 (18.6)47.6 (15.3)48.2 (14.2)47.1 (16.8)
BMI, kg/m2 126.3 (5.4)24.6 (5.0)TA21.2 (5.1)TA21.3 (4.6)A25.1 (5.6)24.2 (5.2)26.4 (5.7)26.8 (6.4)
Race*
White62%T73.4%A89.3%A85.4%A75.9%84.5%52.5%72.6%
Black26.3%13.8%4.9%7.3%14.4%8.7%27.0%8.7%
Other11.7%12.8%5.7%7.3%9.7%6.8%20.5%18.7%
Gender*
Male77.1%A76.6%A62.3%T48.8%75.4%49.5%59.6%60.5%
Female22.9%23.4%37.7%51.2%24.6%50.5%40.4%39.5%
Lung allocation score2  35.9 (15.8)45.3 (11.3)T38.5 (16.4)
MELD, calculated at listing316.9 (8.8)10.9 (6.9)A 17.5 (9.7)
Heart wait-list status*
Status 1A14.7%T10.6%T13.9%
Status 1B23.2%20.2%14.5%
Status 254.8%62.1%54.0%
Old status 17.3%6.9%17.5%
FVC % predicted at listing4  54.4 (25.6)56.6 (21.7)50.4 (19.7)
Dialysis at listing, %42.5%TA3.4%TA0.0%16.7%TA1.2%0.1%77.6%3.5%
History of diabetes, %35.7%TA16.0%33.1%TA40.0%T19.0%13.4%35.8%19.6%
INR 1.60 (0.84)1.32 (0.44)A1.71 (1.65)
Total bilirubin, mg/dL1.93 (3.14)A3.31 (8.01)A5.91 (8.71)
Albumin, mg/dL 3.53 (0.83)A3.26 (0.73)3.02 (0.69)
Wait-list time, days5151 (4,650)TA152 (3,762)T255 (3,312)A223 (4,880)A99 (9,105)5237 (7,099)609 (13 608)140 (7,540)
Time to transplant, days5105 (2,823)TA131 (1,267)TA175 (976)T115 (1,969)A79 (5,815)5181 (3,980)376 (9,536)78 (6,286)
Total transplanted, %656.3%T53.2%T43.4%TA41.4%TA65.0%61.3%47.4%56.2%
STA only, %44.6%45.4%36.9%34.1%
Wait-list mortality: STA versus single organ

Wait-list survival at 1 and 3 years was obtained for SHK (67.4%, 40.8%), SHLi (65.7%, 43.6%), SLuLi (65.7%, 41.0%), and found to be significantly decreased compared to respective thoracic and abdominal controls (p < 0.001). Waitlist survival for SLuK at 1 and 3 years (65.0%, 51.6%) was not statistically different from lung (p = 0.34) or kidney controls (0.41) (Table 4).

Table 4. Wait-list survival for single- and double-organ candidates
 Wait listed patients1-year survival3-year survivalSTA versus thoracic control (p-value)STA versus abdominal control (p-value)
  1. Abbreviations: SHK = simultaneous heart–kidney; SHLi = simultaneous heart–liver; SLuLi = simultaneous lung–liver; SLuK = simultaneous lung–kidney. Significant p-values (p<0.05) in bold.

STA wait-list groups
SHK1,42067.4%40.8%<0.001<0.001
SHLi21865.7%43.6%<0.001<0.001
SLuLi12265.7%41.0%<0.001<0.001
SLuK4165.0%51.6%0.340.41
Single-organ controls
Heart alone72 08474.6%58.3%
Lung alone32 39378.5%58.9%
Kidney alone441 66694.1%77.7%
Liver alone163 60477.1%61.4%

Transplant efficacy: STA versus single-organ controls

STA donor and recipient characteristics

We next reviewed the clinical and demographic data for those candidates who proceeded to STA (Table 5). As noted with the wait-list cohorts, SHK recipients were older than controls (p < 0.01), whereas SLuLi recipients were considerably younger (p < 0.001). STA recipients differed considerably from single-organ recipients with respect to level of acuity at time of transplant. Approximately half of SHK and SHLi were transplanted as hospitalized inpatients, and the majority of these occurred during an ICU admission. This was fewer than those for heart alone, but greater than kidney or liver alone (p < 0.001). SLuLi recipients were also more often hospitalized, and in the ICU, compared to lung alone at the time of transplant (p < 0.001). We also compared measures of abdominal organ dysfuction for STA and control recipients. A similar proportion of SHK and kidney alone recipients were on dialysis preoperatively. INR and total bilirubin were both lower in SHLi and SLuLi in comparison to liver alone as was transplant MELD (p < 0.001). With regard to thoracic organ failure, heart status at time of transplant was slightly more advanced compared to heart alone for SHK and less advanced for SHLi (p < 0.001). There were no significant differences between lung alone and SLuLi or SLuK in terms of LAS or FVC.

Table 5. Comparison of characteristics for STA and single-organ transplant cohorts
nSHKSHLiSLuLiSLuKHeart aloneLung aloneKidney aloneLiver alone
68492421847 44020 384189 03880 332
  • Abbreviations: SHK = simultaneous heart–kidney; SHLi = simultaneous heart–liver; SLuLi = simultaneous lung–liver; SLuK = simultaneous lung–kidney; BMI = body massindex; MELD = model for end-stage liver disease; INR = international normalized ratio.

  • TSignificant (p < 0.05) difference between STA cohort and the associated thoracic-organ control group.

  • ASignificant (p < 0.05) difference between STA cohort and the associated abdominal-organ control group.

  • 1

    BMI > 60 excluded as implausible.

  • 2

    data beginning 5/4/2005.

  • 3

    data beginning 2/27/2002.

  • *

    Chi-squared analysis was performed as a single test with all listed variables; significant test results, if present, are indicated with “T” or “A” in first row only.

Recipient data
Age, years49.3 (13.9)TA44.2 (15.9)32.0 (16.1)TA46.8 (12.9)46.0 (18.6)49.2 (15.0)47.5 (15.0)46.8 (17.1)
BMI, kg/m2 125.5 (5.3)TA24.5 (4.5)A21.3 (4.7)TA22.0 (4.9)A25.0 (5.7)23.4 (5.3)26.2 (5.7)26.9 (6.4)
Race*
White64.5%TA76.1%92.9%88.9%76.7%87.1%51.9%74.0%
Black23.8%13.0%4.8%5.6%%4.8%7.1%29.0%8.8%
Other40.7%10.9%2.4%5.5%5.8%5.8%19.1%17.2%
Gender*        
Male76.9%A76.1%A57.1%T55.6%75.2%52.9%60.6%62.4%
Female23.1%23.9%42.9%44.4%24.8%47.1%39.4%37.6%
Preoperative hospitalization*
Non-ICU, %n20%TA17.4%A23.8%T0%A13.8%6.6%0.3%17.6%
ICU, %n27.8%33.7%14.3%11.1%42.4%5.4%0.2%15.9%
Total, %n47.8%51.1%38.1%38.1%56.2%12.0%0.5%33.5%
Postoperative length of stay, days26 (28)TA29 (22)T38 (36)TA41 (33)TA21 (25)24 (29)9 (15)20 (45)
History of diabetes, %16.2%TA5.4%TA0%TA0%A12.8%10.7%22.1%14.5%
Creatinine, mg/dL4.16 (2.96)TA1.36 (0.72)0.68 (0.31)A2.88 (1.73)TA1.26 (1.13)0.90 (0.89)8.42 (3.42)1.25 (1.07)
Dialysis, %46.2%T1.1%0.0%27.8%T0.3%0.1%42.4%4.2%
Lung allocation score248.73 (17.23)44.99 (6.85)43.82 (15.89)
MELD at transplant313.5 (6.0)10.6 (5.8)19.9 (10.3)
Heart wait-list status*
Status 1A13.5%T5.4%T12.7%
Status 1B24.0%31.5%14.8%
Status 248.6%52.2%48.1%
Old status 110.7%9.8%16.5%
FVC % predicted, at transplant453.68 (21.39)46.25 (14.3)-50.71 (18.08)
INR1.47 (0.53)A1.29 (0.24)A 1.90 (1.67)
Total bilirubin, mg/dL1.90 (2.43)A3.60 (6.6)A 7.83 (10.30)
Albumin, mg/dL3.70 (0.71)A3.12 (0.52) 2.95 (0.73)
Donor data
Age, years30.5 (12.6)TA28.4 (12.9)A28.6 (14.4)A28.5 (15.0)27.8 (14.0)31.3 (14.2)35.7 (17.2)36.1 (18.8)
BMI, kg/m2 125.8 (8.6)T24.9 (4.9)22.6 (3.6)TA23.4 (6.3)24.8 (5.8)24.5 (5.0)26.1 (5.8)25.4 (5.9)
Race*
White68%TA62.0%66.7%A50.0%A72.9%69.5%74.2%72.6%
Black14.3%16.3%26.2%15.8%12.4%15.8%11.6%13.3%
Other17.7%21.7%1.7%33.3%14.7%14.7%14.2%14.1%
Gender
Male69.4%A76.1%A57.1%66.7%69.1%61.6%60.3%60.4%
Female30.6%23.9%42.9%33.3%30.9%38.4%39.7%39.6%
Patient survival for STA and single-transplant control

Kaplan–Meier estimates for 1 and 5 years patient survival were determined for SHK (85.3%, 74.0%), SHLi (85.9%, 74.3%), SLuLi (75.5%, 59.0%) and SLuK (66.7%, 55.6%) (Table 6). In all groups, STA patient survival was not significantly different from thoracic single-transplant cohorts. STA patient survival was however lower than abdominal single-transplant groups for SHK (p < 0.001), SLuLi (p = 0.01) and SLuK (p < 0.001). SHLi had the greatest 1 and 5 years survival of the STA cohorts, and was unique in that survival was equivalent to the abdominal control group (p = 0.81). It was also notable that STA combinations with kidney had lower survival compared to STA combinations with liver (SHK vs. SHLi; SLuK vs. SLuLi). This may be due to baseline differences between the kidney and liver STA cohorts in terms of age (liver cohorts are younger), number of associated comorbidities or severity of organ dysfunction at time of transplant. It is also possible that this is related to differences in manifestations of systemic illness for kidney and liver failure.

Table 6. Posttransplant survival for STA and control recipients
 Transplant recipients1-year survival5-year survivalSTA versus thoracic control (p-value)STA versus abdominal control (p-value)
  1. Abbreviations: SHK = simultaneous heart–kidney; SHLi = simultaneous heart–liver; SLuLi = simultaneous lung–liver; SLuK = simultaneous lung–kidney. Significant p-values (p<0.05) in bold.

STA cohorts
SHK68485.3%74.0%0.27<0.001
SHLi9285.9%74.3%0.560.81
SLuLi4275.5%59.0%0.640.01
SLuK1866.7%55.6%0.46<0.001
Single-organ controls
Heart alone47 44085.4%71.3%
Lung alone20 38480.0%49.8%
Kidney alone189 03895.2%83.7%
Liver alone80 33286.9%74.2%
Survival Benefit of STA

A multivariable Cox regression model was created to explore the potential survival benefit of a STA transplant, compared to remaining on the wait-list. Among SHK, SHLi and SLuLi a substantial increase for STA was achieved (SHK, HR 0.31, 95% CI 0.26–0.37, p < 0.001; SHLi, HR 0.34, 95% CI 0.21–0.56, p < 0.001; SLuLi HR 0.53, 95% CI 0.29–0.96, p = 0.04). (Figure 1). SLuK recipients did not incur any transplant survival benefit over wait-list patients (HR 1.05, 95% CI 0.45–2.47, p = 0.91).

image

Figure 1. Survival benefit of transplantation for STA candidates. Survival for wait-list patients is compared to posttransplant survival for each of the STA subtypes. Hazard ratios (HR) and 95% confidence intervals (CI) were derived from multivariate Cox regression models comparing the two curves.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. References

Limited life-saving resources can be rationed according to different strategies, each with unique ethical quandaries. These strategies typically aim to strike balances between core principles that reflect society's values, but that may conflict with one another in particular scenarios [12]. Deceased-donor organ allocation in the United States aims to balance the principles of justice and utility: The goal is to treat those with the greatest urgency, while maximizing benefit from available organs. The balance is not always even; for example, the allocation policies for some organs, particularly liver and heart, prioritize urgency as the primary determinant, and therefore emphasize justice over utility. STA is an example in which the principles of justice and utility could each suggest different allocation results, as two life-saving organs are allocated to one individual who is presumed to have a higher medical urgency. In the setting of a constrained resource and increasing number of STAs, this analysis explores STA in the context of the guiding principles of organ allocation, justice and utility, to determine if assumptions used to validate STA fulfill the objectives as outlined by the transplantation community.

Complexities in STA allocation

STA recipients are allocated organs according to a UNOS policy, which states that once the candidate becomes eligible for the first organ, “the second required organ shall be allocated to the multiple organ candidate from the same donor if the donor is located with the same local organ distribution unit where the multiple organ candidate is registered [13].” National policy therefore dictates that STA allocation should proceed according to the organ with greater priority. In practice, allocation schemes for each organ differ slightly, such that heart–liver allocation would involve a different geographical distribution depending upon whether it follows the heart or the liver. Additionally, the severity of illness for patients with multiple-organ failure may not be accurately described in single-organ models [14]. These complexities may delay allocation, thereby contributing to longer wait-list times and higher mortality for STA candidates.

Justice: STA candidates have a greater medical urgency than single-organ candidates

The principle of justice as rationale for STA assumes that STA candidates have a greater urgency than single-organ recipients, but the notion that patients with two failing organs would sustain a greater risk of death compared to patients with a single failing organ has not previously been addressed [15]. As noted above, according to UNOS policy, a second organ is allocated to the STA candidate regardless of wait-list status for that second organ. For example, once an SHLi candidate with a relatively low MELD score has been allocated a heart, a liver is allocated from the same donor, thereby bypassing liver-only patients with greater MELD scores and associated risk of wait-list mortality. Similarly, SHK candidates who have been recently wait-listed and are not yet on dialysis may receive kidneys ahead of patients on chronic hemodialysis with substantially longer wait-list times.

These scenarios raise the possibility that the presumed difference in medical urgency between STA and non-STA patients is overstated. We therefore sought to determine whether the principle of justice truly applies to STA by examining wait-list outcomes. These analyses indicated that for multiple STA combinations—SHK, SHLi and SLuLi—survival on the wait-list is indeed markedly reduced when compared to candidates awaiting a single organ. From these data, one could argue that a more aggressive protocol for prioritizing STA patients on the wait-list is required in order to minimize wait-list death. Such a protocol would also need to consider the impact on the outcomes of single-organ candidates who are bypassed by STA allocation, an additional concern that is beyond the scope of this paper. Support for the continued practice of STA from our data is also provided by the demonstration of a clear survival benefit for transplantation among SHK, SHLi and SLuLi compared to remaining on the wait-list. It is notable that the survival benefit among SHK, SHLi and SLuLi is not too dissimilar to the survival benefit of a kidney after nonrenal transplant, a practice that like STA may not align with the goals of organ allocation [16, 17].

Utility: patient survival after STA and non-STA

Multiple organ transplantation in a single recipient cannot be easily defended on the merit of utility, at least when utility refers to the total number of lives saved. However, utility also considers efficacy, which includes measures such as patient or graft survival, total life-years saved or quality-of-life. An outcomes-based approach to utility has been applied to a range of scenarios including the debate over heart or liver retransplantation [18]. As with STA, heart or liver retransplantation involves allocation of a second (or third, fourth, etc.) organ to a single patient while others wait for their first transplant. In a review of ethical considerations for retransplantation, Ubel et al. concluded that, while retransplantation is defensible on grounds of extreme medical urgency, these arguments ultimately rely on an assumption that outcomes are at least equivalent to primary transplantation. Since this is not the case—as a whole, retransplantation has inferior outcomes compared to the initial transplant—the authors reject the practice and recommend limitations to organ retransplantation.

It therefore stands to reason that STA can be justified for a selected group of patients as long as successful outcomes can be achieved. In this regard, STA differs importantly from retransplantation in that most of the published data available from single-centers (Table 7) and multicenter/national reviews (Table 8), though hindered by a limited number of subjects, support the notion that STA recipients survive at least as long as patients with single-transplants. Our findings are aligned with prior published data to the extent that we have shown equivalent survival for STA recipients and single-organ thoracic controls; however, we did not find that this equivalency extended to the abdominal organ, except in the scenario of SHLi.

Table 7. Single-center outcomes for STA transplantation
TypeAuthorDateHospitalGroupPatients (N)Patient survival (%)p-value8
1 year5 year10 year
  • Abbreviations: SHK = simultaneous heart–kidney; SHLi = simultaneous heart–liver; SLuLi = simultaneous lung–liver; SLuK = simultaneous lung–kidney; IHT = isolated heart transplantation; IKT = isolated kidney transplantation; ILiT = isolated liver transplantation; ns = not significant.

  • 1

    Number of significant figures corresponds to those reported in the referenced texts.

  • 2

    Numerical values estimated from graph, not explicitely reported in text.

  • 3

    Listed values represent 4-year patient survival.

  • 4

    Listed values represent 3-year patient survival.

  • 5

    Listed values represent 1-month patient survival.

  • 6

    Listed values represent 6-year patient survival.

  • 7

    Two patients with simultaneous heart–kidney-liver; one patient with simultaneous heart–lung–liver.

  • 8

    All p-values reflect testing between STA and single-organ control KM survival curves.

SHKKocher et al.1998University of ViennaSHK9881, 2882, 3 
    IHT379802602, 3ns
    IKT769932832, 3ns
SHKBlanche et al.2001Cedars-SinaiSHK1010055 
    IHT16992710.37
    IKT393
SHKLeeser et al.2001Temple UniversitySHK137760 
    IHT6008067 
    IKT 
SHKLuckraz et al.2003Papworth HospitalSHK137767 
    IHT76082580.68
    IKT
SHKGroetzner et al.2005Ludwig Maximilians UniversitySHK139292 
    IHT22188840.42
    IKT
SHKHermsen et al.2007University of WisconsinSHK19902822 
    IHT5118827520.90
    IKT31889728620.20
SHKBruschi et al.2007Niguarda Ca' Granda HospitalSHK988.977.864.8 
    IHT71187.078.163.0 
    IKT 
SHKHsu et al.2008National Taiwan UniversitySHK1353.946.24 
    IHT24883.770.940.13
    IKT
SHKRaichlin et al.2011Mayo ClinicSHK12835836 
    IHT1839557960.61
    IKT
SHKKebschull et al.2012University of MuensterSHK131001004 
    IHT 
    IKT13100924ns
SHLiRaichlin et al.2009Mayo ClinicSHLi1571007560 
    IHT2589383650.39
    ILiT12019483700.44
Table 8. Multicenter outcomes for STA transplantation
TypeAuthorPubDateSourceGroupPatients (N)Patient survival (%)p-value8
1 yr5 yr10 yr
  • Abbreviations: SHK = simultaneous heart–kidney; SHLi = simultaneous heart–liver; SLuLi = simultaneous lung–liver; SLuK = simultaneous lung–kidney; IHT = isolated heart transplantation; IKT = isolated kidney transplantation; ILiT = isolated liver transplantation; ILuT = isolated lung transplantation =ILuT; UNOS = United Network for Organ Sharing; ISHLT = International Society for Heart and Lung Transplantation; ns = not significant.

  • 1

    Number of significant figures corresponds to those reported in the referenced texts.

  • 2

    Listed values represent 2-year patient survival.

  • 3

    Numerical values estimated from graph, not explicitely reported in text.

  • 4

    Listed values represent 3-year patient survival.

  • 5

    Patient number is not specified; corresponds to available UNOS record 2001–2002 (1 year) or 1997–1998 (5 year)

  • 6

    Patient number is not specified; corresponds to UNOS data as of March.

  • 7

    2002 French multicenter study involving 3 centers: Henri-Mondor University Hospital, Louis Pradel University Hospital and La Pitie University Hospital.

  • 8

    All p-values reflect log-rank testing between STA and single-organ controls.

SHKNarula et al.1997ISHLT/UNOSSHK IHT IKT82 14 34076.41 82.866.52 78.620.20
SHKTaylor et al.2005ISHLTSHK IHT IKT336 58 343823 793683 723563 483
SHKVermes et al.2009France7SHK IHT IKT67 298162.0 71.053.3 60.146.5 47.20.60
SHKGill et al.2009UNOSSHK IHT IKT263 16 710 68 83384.0 86.9 94.577.44 76.54 85.03, 40.67 <0.001
SHLiTe et al.2008UNOSSHLi IHT ILiT47 not stated5 not stated585 86 8875 72 74 
SHLiCannon et al.2012UNOSSHLi IHT ILiT97 67 852 96 03384.4 83.3 85.472.3 64.8 72.40.54 0.13
SLuLiBarshes et al.2005UNOSSLuLi ILuT ILiT11 not stated6 62 67679.0 78.4 83.263.03 59.93 76.430.59

Prior reported outcomes

Among the different STA combinations, SHK is most commonly performed. Over a period of 14 years (1998–2011), nine different reports from single-centers compared SHK outcomes to those of single-heart transplants and six have shown statistically equivalent patient survival (1-year: 75–100%; 5-year: 55–92%) [2, 4-7, 19-22]. (Table 7). Overall, these single-center findings agree with the body of multicenter data (UNOS, ISHLT and France) [1, 23-25]. (Table 8) There are fewer published comparisons between SHK and kidney-alone transplantation. Several prior single-center series reported equivalent patient survival; however, results from Gill et al. demonstrated a higher mortality rate for SHK recipients, particularly during the first year posttransplant [20, 22, 25].

Our findings are also in agreement with the available literature on SHLi recipients. In a series of SHLi recipients between 1992 and 2007, Raichlin et al. reported 1 and 5 years patient survival for SHLi (N = 15, 100%; 75%) that was not significantly different in comparison to heart (N = 258, 93%; 83%) and liver-alone recipients (N = 1201, 94%; 83%, p = 0.44). In a UNOS review (1987–2005), Te et al. found no difference in 1 and 5 years patient survival (N = 47, 85%; 75%) when compared to heart (86%; 72%) and liver-alone patients (88%; 74%) [26]. A recent followup by Cannon et al. reported similar values with a larger UNOS cohort (N = 97) [27]. All three of these reviews differ from our study in that they included triple-organ recipients in the survival analyses.

A single study by Barshes et al. has examined national outcomes for SLuLi, and found no difference in survival 1 and 5 years between SLuLi (N = 11, 79%, 63%) and liver-alone (N = 62 676, 83%, 71%, p = 0.59). This series did not include statistical analyses comparing SLuLi and lung-alone (1 year: 78%, 3 year: 60%) though they appeared comparable. There are no single-center series with associated control comparisons for SLuLi or SLuK. Couetil et al. reviewed an SLuLi experience of 10 patients with cystic fibrosis and reported 70% survival at 1 and 3 years [28]. This was similar to Grannas et al., who reported a series of 13 SLuLi patients whose 1 and 3 years survivals were 69% and 62% [29].

Study limitations and conclusions

Our study has several limitations. First, it is limited by the drawbacks inherent to retrospective cohort studies, namely a lack of granularity and the inability to control for key confounders. Small sample size, particularly for SLuK wait-list and transplant populations, may have also limited the utility of statistical testing. Inherently, the STA population with two dysfunctional organs is different from single-organ recipients. STA recipients are a highly selected group of patients whose clinical features may not closely match those of the single-transplant patients, and who carry a heavier burden of illness due to multiorgan failure. These baseline differences in STA versus abdominal-only transplant recipients limit our conclusions regarding posttransplant survival. The national STA cohorts are heterogeneous with respect to patient selection, surgical technique and specifics of clinical management, which can vary amongst institutions. An analysis of survival benefit assumes that the wait-list and transplant populations are similar, aside from the treatment effect of transplantation. However the process of spending time as a candidate and being selected as a suitable recipient may in fact actually represent differentiation between the two cohorts, a limitation that has been recognized by other authors utilizing this modeling technique.

In summary, our results indicate that (1) patients wait-listed for SHK, SHLi and SLuLi (but not SLuK) transplantation have a greater risk of wait-list removal than candidates awaiting only one organ and a significant survival benefit if transplanted; (2) posttransplant STA recipient survival is equivalent to thoracic-alone transplantation in all groups; (3) SHK, SLuLi and SLuK recipient survival is less than abdominal-alone transplantation; (4) SHLi recipient survival is equivalent to both thoracic and abdominal organ controls. Combined with a lower survival rate experienced on the wait-list, the benefit of transplantation, at least when compared to thoracic recipients, is greater for STA patients. Put another way, these patients simply do not have the same luxury of time while waiting for organs but have potential to experience similar results if they survive to transplant. Criteria for prioritizing STA candidates, including modifications to the current allocation protocols, may need to be considered in order to reduce disparity in wait-list survival. On the other hand, these data raise ethical questions about whether distribution of deceased kidney and liver allografts to certain STA groups (SHK, SLuLi, SLuK) is truly the most efficacious use of these scarce resources, because it leads to inferior outcomes compared to single abdominal organ transplantation. In this regard SHLi transplantation appears uniquely justifiable, with encouraging results at least supporting SHLi transplant as an effective option to a select group of patients.

Disclosures

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. References

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. References
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