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Renal allograft survival in patients who had simultaneous liver and kidney transplantation compared with those who had renal transplantation alone
Renal Allograft Survival in Patients Who Had Simultaneous Liver and Kidney Transplantation Compared With Those Who Had Renal Transplantation Alone S.P. Nair, M. Krishnan, P. Scheel, and P.J. Thuluvath
I
T HAS been suggested that simultaneous liver and kidney transplantation (SLK) may protect the renal allograft by host microchimerism induced by passenger leukocytes, or by the neutralization of preformed antibodies and cytotoxic lymphocytes by the newly grafted liver. However, the data available so far have been conflicting and it remains unclear whether a combined liver and kidney transplantation confers any protection to renal allograft in clinical situation where a combined transplantation becomes necessary.1–5 The aim of this study was to compare the graft and patient survival among those who had undergone simultaneous (from a single donor) or sequential (kidney after a previous liver from a different donor) transplantation with cadaver kidney transplantation alone. PATIENTS AND METHODS Data from United Network of Organ Sharing (UNOS) from 1990 to 1996 was used for the study. Three groups of patients were identified: (1) patients who had SLK (n ⫽ 465); (2) kidney after liver (KAL; n ⫽ 134); and (3) cadaver kidney alone (CK, n ⫽ 47,013). The following data were collected: age, sex, race distribution of the donors and recipients, cold ischemia time, primary kidney disease, graft and patient survival at 30 days and 2 years, and retransplantation rates at the end of 2 years after the initial transplantation.
Statistical Analysis Chi-square test, Student’s t test, logistic regression analysis, and Cox proportional hazard model were used as appropriate.
RESULTS
The patient and donor characteristics are shown in Table 1. There was no difference in age or sex between the SLK and CK, but patients in KAL group were older. Only 10% of patients who had SLK were African-American compared to 25% of those who had CK; this difference was highly significant (P ⬍ .001). Donor age (P ⫽ .02) and cold ischemia time (P ⫽ .001) were significantly lower in patients who had CLK compared with the other two groups (Table 1). Sixty-one percent of the SLK group had normal creatinine at the time of discharge from the hospital compared to 35% in the CK and 48% in the KAL group. The indications for kidney transplantation varied greatly between the groups. The most common indication for SLK was hepatoFrom the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Address reprint requests to Dr P.J. Thuluvath, The Johns Hopkins University School of Medicine, 1830 E. Monument Street, Room 429, Baltimore, MD 21205.
Table 1. Patient and Donor Characteristics and Graft and Patient Survival in Different Groups SLK (N ⫽ 465)
Age (y)
43.0 ⫾ 16.8
Sex (% male:female) Race (blacks/whites) Cold ischemia time (h)
60:40 40/363 15.5 ⫾ 7.6
Donor age (y)
31.2 ⫾ 16.3
Normal creatinine† Graft survival at 30 days Graft survival at 2 years Retransplantation rate Patient survival at 2 years
61% 85% 59% 1% 67%
CK (n value)* (N ⫽ 37,103)
43.6 ⫾ 14.0 (NS) 61:39 (NS) 12019/27615 22.6 ⫾ 9.9 (0.001) 32.9 ⫾ 16.8 (0.02) 35% (0.02) 94% (0.001) 80% (0.001) 1.3% (NS) 90% (0.0001)
KAL (P value)* (N ⫽ 134)
48.4 ⫾ 16.8 (0.001) 66:34 (NS) 13/105 19.4 ⫾ 14 (0.001) 36.2 ⫾ 17.3 (0.002) 48% (0.008) 92% (0.005) 74% (0.004) 1.5% (NS) 82.9% (0.001)
SLK, simultaneous liver and kidney; KAL, kidney after liver; CK, cadaveric kidney transplantation alone. *P value when compared with SLK; NS, not significant. † Normal creatinine at the time of discharge ⱕ 132.6 mol/L (1.5 mg/dL).
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/01/$–see front matter PII S0041-1345(00)02462-3 1139
Transplantation Proceedings, 33, 1139–1140 (2001)
1140
renal syndrome followed by polycystic disease. The common causes of renal failure in patients who had CK were diabetes, hypertensive nephroscelorsis, chronic glomerolonephritis, and polycystic kidney disease. The most common indication for KAL group was cyclosporine induced renal failure. Thirty-day and 2-year graft survival with SLK were 85% and 59%, respectively, compared to 94% and 80% for kidney alone. By logistic regression, using graft survival at 2 years as the dependent variable, SLK was a predictor (odds ratio of 0.21, CI 0.17 to 0.25) of poor graft survival at 2 years after adjusting for recipient’s age and sex, donor age, and cold ischemia time. Two-year patient survival was 67% in the SLK group compared to 90% in the CK group. KaplanMeier analysis for patient survival showed a significantly lower survival for the SLK group (P ⬍ .0001). Survival rates for patients in the KAL group were lower than the CK group, but significantly higher compared to SLK group. Using the Cox regression model, the hazard ratio for SLK group was 2.49 (95% CI 1.88, 4.53) for patient survival (P ⬍ .0001), whereas KAL, recipient sex, cold ischemia time, and donor age were not significant. There were no differences in the retransplantation rates at the end of 2 years between the three groups (Table 1). The 2-year patient survival rate for isolated liver transplantation during the study period was 79.4%, which was again significantly higher than the 67% for the SLK group. DISCUSSION
Patients with SLK had favorable factors such as a lower donor age, a shorter period of cold ischemia, and a lower proportion of African Americans. Despite these favorable factors, analysis of UNOS data suggest that the patients who had simultaneous liver and kidney transplantation had a 2-year graft survival that was significantly lower than a contemporary groups of patients who had cadaver kidney transplantation alone or a kidney transplantation after a liver transplantation. These observations are even more significant when we consider the fact that the indication for renal transplantation in many patients in the SLK group was hepatorenal syndrome where there was a high probability of spontaneous recovery of native kidneys and a very low probability of disease recurrence. Previous publications on this topic, based on single-
NAIR, KRISHNAN, SCHEEL ET AL
center experiences, have produced conflicting results. This was to be expected; patients who received combined liver and kidney were a heterogeneous group. Moreover, the patient selection for combined liver and kidney transplantation is likely to vary significantly between centers. These differences alone could explain the conflicting results reported in the literature. Our data clearly show that, in clinical situation where a combined transplantation is required, the liver does not provide any additional protection for a simultaneously transplanted kidney from rejection as evidenced by a lower graft survival at 30 days and 2 years. The findings of our study are similar to a previous study that used UNOS data to compare combined liver kidney transplant to a group who received the contra lateral kidney from the same donor.5 The most likely explanation for this observation, contrary to the experimental evidence, would be that the patients who required SLK were sicker with comorbid illnesses such as diabetes and hypertension in addition to liver failure. Moreover, patients who received SLK were more likely to have had recurrent infections, longer intensive care stay, multi-organ dysfunction, and abrupt changes in hemodynamic and fluid status. The patient survival analysis from our study needs to be interpreted carefully. Being a sicker group of patients, the overall survival among SLK patients was lower compared to CK patients. However, 67% of patients were alive at 2 years, and this observation suggests that combined liver and kidney transplantation is a viable option for patients with advanced cirrhosis and renal failure. ACKNOWLEDGMENT We sincerely thank UNOS for allowing us to use their database for this study.
REFERENCES 1. Jeyarajah DR, Gonwa TA, McBride M, et al: Transplantation 64:1760, 1997 2. Larue JR, Hiesse C, Samuel D, et al: Transplant Proc 29:2365, 1997 3. Chui AK, De Leon C, Rao AR, et al: Transplant Proc 30:3256, 1998 4. Morrissey PE, Gordon F, Shaffer D, et al: Liver Transpl Surg 4:363, 1998 5. Katznelson S, Cecka JM: Transplantation 61:1403, 1996
I
T HAS been suggested that simultaneous liver and kidney transplantation (SLK) may protect the renal allograft by host microchimerism induced by passenger leukocytes, or by the neutralization of preformed antibodies and cytotoxic lymphocytes by the newly grafted liver. However, the data available so far have been conflicting and it remains unclear whether a combined liver and kidney transplantation confers any protection to renal allograft in clinical situation where a combined transplantation becomes necessary.1–5 The aim of this study was to compare the graft and patient survival among those who had undergone simultaneous (from a single donor) or sequential (kidney after a previous liver from a different donor) transplantation with cadaver kidney transplantation alone. PATIENTS AND METHODS Data from United Network of Organ Sharing (UNOS) from 1990 to 1996 was used for the study. Three groups of patients were identified: (1) patients who had SLK (n ⫽ 465); (2) kidney after liver (KAL; n ⫽ 134); and (3) cadaver kidney alone (CK, n ⫽ 47,013). The following data were collected: age, sex, race distribution of the donors and recipients, cold ischemia time, primary kidney disease, graft and patient survival at 30 days and 2 years, and retransplantation rates at the end of 2 years after the initial transplantation.
Statistical Analysis Chi-square test, Student’s t test, logistic regression analysis, and Cox proportional hazard model were used as appropriate.
RESULTS
The patient and donor characteristics are shown in Table 1. There was no difference in age or sex between the SLK and CK, but patients in KAL group were older. Only 10% of patients who had SLK were African-American compared to 25% of those who had CK; this difference was highly significant (P ⬍ .001). Donor age (P ⫽ .02) and cold ischemia time (P ⫽ .001) were significantly lower in patients who had CLK compared with the other two groups (Table 1). Sixty-one percent of the SLK group had normal creatinine at the time of discharge from the hospital compared to 35% in the CK and 48% in the KAL group. The indications for kidney transplantation varied greatly between the groups. The most common indication for SLK was hepatoFrom the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Address reprint requests to Dr P.J. Thuluvath, The Johns Hopkins University School of Medicine, 1830 E. Monument Street, Room 429, Baltimore, MD 21205.
Table 1. Patient and Donor Characteristics and Graft and Patient Survival in Different Groups SLK (N ⫽ 465)
Age (y)
43.0 ⫾ 16.8
Sex (% male:female) Race (blacks/whites) Cold ischemia time (h)
60:40 40/363 15.5 ⫾ 7.6
Donor age (y)
31.2 ⫾ 16.3
Normal creatinine† Graft survival at 30 days Graft survival at 2 years Retransplantation rate Patient survival at 2 years
61% 85% 59% 1% 67%
CK (n value)* (N ⫽ 37,103)
43.6 ⫾ 14.0 (NS) 61:39 (NS) 12019/27615 22.6 ⫾ 9.9 (0.001) 32.9 ⫾ 16.8 (0.02) 35% (0.02) 94% (0.001) 80% (0.001) 1.3% (NS) 90% (0.0001)
KAL (P value)* (N ⫽ 134)
48.4 ⫾ 16.8 (0.001) 66:34 (NS) 13/105 19.4 ⫾ 14 (0.001) 36.2 ⫾ 17.3 (0.002) 48% (0.008) 92% (0.005) 74% (0.004) 1.5% (NS) 82.9% (0.001)
SLK, simultaneous liver and kidney; KAL, kidney after liver; CK, cadaveric kidney transplantation alone. *P value when compared with SLK; NS, not significant. † Normal creatinine at the time of discharge ⱕ 132.6 mol/L (1.5 mg/dL).
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/01/$–see front matter PII S0041-1345(00)02462-3 1139
Transplantation Proceedings, 33, 1139–1140 (2001)
1140
renal syndrome followed by polycystic disease. The common causes of renal failure in patients who had CK were diabetes, hypertensive nephroscelorsis, chronic glomerolonephritis, and polycystic kidney disease. The most common indication for KAL group was cyclosporine induced renal failure. Thirty-day and 2-year graft survival with SLK were 85% and 59%, respectively, compared to 94% and 80% for kidney alone. By logistic regression, using graft survival at 2 years as the dependent variable, SLK was a predictor (odds ratio of 0.21, CI 0.17 to 0.25) of poor graft survival at 2 years after adjusting for recipient’s age and sex, donor age, and cold ischemia time. Two-year patient survival was 67% in the SLK group compared to 90% in the CK group. KaplanMeier analysis for patient survival showed a significantly lower survival for the SLK group (P ⬍ .0001). Survival rates for patients in the KAL group were lower than the CK group, but significantly higher compared to SLK group. Using the Cox regression model, the hazard ratio for SLK group was 2.49 (95% CI 1.88, 4.53) for patient survival (P ⬍ .0001), whereas KAL, recipient sex, cold ischemia time, and donor age were not significant. There were no differences in the retransplantation rates at the end of 2 years between the three groups (Table 1). The 2-year patient survival rate for isolated liver transplantation during the study period was 79.4%, which was again significantly higher than the 67% for the SLK group. DISCUSSION
Patients with SLK had favorable factors such as a lower donor age, a shorter period of cold ischemia, and a lower proportion of African Americans. Despite these favorable factors, analysis of UNOS data suggest that the patients who had simultaneous liver and kidney transplantation had a 2-year graft survival that was significantly lower than a contemporary groups of patients who had cadaver kidney transplantation alone or a kidney transplantation after a liver transplantation. These observations are even more significant when we consider the fact that the indication for renal transplantation in many patients in the SLK group was hepatorenal syndrome where there was a high probability of spontaneous recovery of native kidneys and a very low probability of disease recurrence. Previous publications on this topic, based on single-
NAIR, KRISHNAN, SCHEEL ET AL
center experiences, have produced conflicting results. This was to be expected; patients who received combined liver and kidney were a heterogeneous group. Moreover, the patient selection for combined liver and kidney transplantation is likely to vary significantly between centers. These differences alone could explain the conflicting results reported in the literature. Our data clearly show that, in clinical situation where a combined transplantation is required, the liver does not provide any additional protection for a simultaneously transplanted kidney from rejection as evidenced by a lower graft survival at 30 days and 2 years. The findings of our study are similar to a previous study that used UNOS data to compare combined liver kidney transplant to a group who received the contra lateral kidney from the same donor.5 The most likely explanation for this observation, contrary to the experimental evidence, would be that the patients who required SLK were sicker with comorbid illnesses such as diabetes and hypertension in addition to liver failure. Moreover, patients who received SLK were more likely to have had recurrent infections, longer intensive care stay, multi-organ dysfunction, and abrupt changes in hemodynamic and fluid status. The patient survival analysis from our study needs to be interpreted carefully. Being a sicker group of patients, the overall survival among SLK patients was lower compared to CK patients. However, 67% of patients were alive at 2 years, and this observation suggests that combined liver and kidney transplantation is a viable option for patients with advanced cirrhosis and renal failure. ACKNOWLEDGMENT We sincerely thank UNOS for allowing us to use their database for this study.
REFERENCES 1. Jeyarajah DR, Gonwa TA, McBride M, et al: Transplantation 64:1760, 1997 2. Larue JR, Hiesse C, Samuel D, et al: Transplant Proc 29:2365, 1997 3. Chui AK, De Leon C, Rao AR, et al: Transplant Proc 30:3256, 1998 4. Morrissey PE, Gordon F, Shaffer D, et al: Liver Transpl Surg 4:363, 1998 5. Katznelson S, Cecka JM: Transplantation 61:1403, 1996