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Simultaneous pancreas-kidney transplant compared with kidney transplant in Type I diabetic patients with end-stage renal disease
Simultaneous Pancreas-Kidney Transplant Compared With Kidney Transplant in Type I Diabetic Patients With End-Stage Renal Disease R. Pe´rez, M.D. Navarro, D. del Castillo, R. Santamarı´a, J. Padillo, J.C. Regueiro, and P. Aljama
I
N OUR SECTIONS, diabetic nephropathy as a result of Type I diabetes mellitus is the etiology of end-stage renal disease in 6% of patients on a dialysis program and in 8.7% of kidney transplant patients. This group of patients can benefit from a simultaneous pancreas-kidney transplant rather than a kidney transplant alone. This type of transplant eliminates the need for dialysis and therapy with insulin,1 as well as stabilizing retinopathy,2,3 neuropathy, and diabetic nephropathy.4,5 The aim of this article is to compare the results of simultaneous pancreas-kidney transplant with those of kidney transplant alone in patients with end-stage renal disease secondary to Type I diabetes mellitus, assessing the number of rejections, kidney graft function, kidney and pancreas graft survival, and patient survival during the first 2 posttransplant years. PATIENTS AND METHODS Between March 1983 and May 2001 we studied a total of 44 transplants performed on 42 diabetic patients, of which 15 were kidney transplants (two of which received a second kidney graft) and 29 were simultaneous pancreas-kidney transplants. All patients received grafts from cadaver donors. Azathioprine, cyclosporine, and corticoids were used as immunosuppressants in the majority of patients. Thirteen patients (2 kidney transplants and 11 simultaneous pancreas-kidney transplants) received tacrolimus, and fifteen (4 kidney transplants and 11 simultaneous pancreas-kidney transplants) received mycophenolate. In the simultaneous pancreas-kidney transplant group, induction with antibodies was used with OKT3 up to 1995, and with ATGAM from 1996 to 1998; recently, antiCD25 (Simulect) was used in two patients. For the statistical analyses, the chi-square test was used for qualitative variables, and the Student’s t test for quantitative variables. The Kaplan-Meier method was used to calculate actuarial survival, and the Log Rank test to compare survival between the two groups.
RESULTS
In demographic terms, no significant differences were observed as regards recipient age in the simultaneous pancreas-kidney transplant group (37.8 ⫾ 5.6 years) when compared with the kidney transplant group (41.8 ⫾ 9.4 years). The same occurred with gender (22 males and 7 females in the simultaneous pancreas-kidney transplant group, 10 males and 5 females in the kidney transplant group) and with the local extraction rate. However, a difference was
found (P ⫽ .02) in donor age, which was significantly lower in the simultaneous pancreas-kidney transplant group (24.9 ⫾ 10.8 years) when compared with the kidney transplant group (38.5 ⫾ 17 years). Hospital stays were significantly longer in the simultaneous pancreas-kidney transplant group (48.6 ⫾ 34.6 days) than in the kidney transplant group (18 ⫾ 11 days) (P ⬍ .01). This coincides with other published studies.6,7 The simultaneous pancreas-kidney transplant group underwent fewer cold ischemia hours (16.4 ⫾ 6.1 hours) than the kidney transplant group (22 ⫾ 8.8 hours; P ⬍ .02). The HLA-DR mismatch was significantly greater in simultaneous pancreas-kidney transplants (P ⫽ .001), with no differences observed in the percentage of reactivity to the panel, nor in HLA-A and HLA-B. The percentage of rejection in simultaneous pancreaskidney transplants was 20.6%, compared with 40% in kidney transplants (n.s.). There were no differences between both groups in plasmatic creatinine 3, 6, 12, and 24 months after transplant. Two years after transplant, kidney graft survival rate in kidney transplants was 73% and 81% in the simultaneous pancreas-kidney transplant group (P ⬍ .05). The causes of graft loss in kidney transplants were two thrombosis, one chronic rejection, and one due to cyclosporine toxicity. In the simultaneous pancreas-kidney transplant group, there was one due to chronic nephropathy, one to acute rejection, and one to thrombosis. Pancreas graft survival 2 years after transplant was 75%. Causes of loss were due in three cases to pancreatitis and in one to a thrombosis of the graft. Complications in the simultaneous pancreas-kidney transplant group were one ureteral stenosis, two urethral stenosis, two bladder fistulas, repeated pancreatitis in two patients (in whom pancreatic exocrine drainage was reconverted from bladder drainage to enteric drainage), and two duodenal segment leak. Patient survival in kidney transplants was 86% and 92% in simultaneous pancreaskidney transplants (P ⫽ .07). Causes of death in the kidney From the Nephrology, Surgery and Urology Sections, Reina Sofia Hospital, Co´rdoba, Spain. Address reprint requests to R. Perez, MD, Reina Sofia Hospital, Nephrology, Surgery and Urology Section, Avda Menendez Pidal s/n, 14004 Cordoba, Spain.
0041-1345/01/$–see front matter PII S0041-1345(01)02412-5
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
3494
Transplantation Proceedings, 33, 3494–3495 (2001)
PANCREAS-KIDNEY TRANSPLANT
transplant group were: one due to sepsis, one to acute myocardial infarction, and one to malignancy; and in simultaneous pancreas-kidney transplants, one due to sepsis.
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group, as a large part of them were transplanted more recently than the kidney transplants. REFERENCES
DISCUSSION
Type I diabetes mellitus patients who receive a simultaneous pancreas-kidney transplant show acute rejection, kidney graft function, and patient survival rates that are comparable with those of diabetic patients receiving kidney transplants. However, morbidity is greater in the simultaneous pancreas-kidney transplant group, as are complications, particularly in the first posttransplant year, which is reflected by longer hospital stays. This has been observed in previous series. Graft survival is significantly greater in the simultaneous pancreas-kidney transplant group than in the kidney transplant group, probably due to the new immunosuppression used in the majority of the patients in this
1. Nathan DM, Fogel H, Norman D, et al: Transplantation 52:85, 1991 2. Scheider A, Meyer-Schwickerath E, Nusser J, et al: Diabetologia 34 (Suppl 1):S95, 1991 3. Konigssrainer A, Miller K, Steurer W, et al: Diabetologia 34 (Suppl 1):S86, 1991 4. Fioretto P, Steffes MW, Sutherland DE, et al: N Engl J Med 339:69, 1998 5. Navarro X, Sutherland DE, Kennedy WR: Ann Neurol 42:727, 1997 6. Sollinger HW, Odorico JS, et al: Ann Surg 228:284, 1998 7. Cheung AHS, Sutherland DER, Gilligham KJ, et al: Kidney Int 41:924, 1992 8. Sutherland DER, Gruessner RWG, Gores PF: Transplant Rev 8:185, 1994
I
N OUR SECTIONS, diabetic nephropathy as a result of Type I diabetes mellitus is the etiology of end-stage renal disease in 6% of patients on a dialysis program and in 8.7% of kidney transplant patients. This group of patients can benefit from a simultaneous pancreas-kidney transplant rather than a kidney transplant alone. This type of transplant eliminates the need for dialysis and therapy with insulin,1 as well as stabilizing retinopathy,2,3 neuropathy, and diabetic nephropathy.4,5 The aim of this article is to compare the results of simultaneous pancreas-kidney transplant with those of kidney transplant alone in patients with end-stage renal disease secondary to Type I diabetes mellitus, assessing the number of rejections, kidney graft function, kidney and pancreas graft survival, and patient survival during the first 2 posttransplant years. PATIENTS AND METHODS Between March 1983 and May 2001 we studied a total of 44 transplants performed on 42 diabetic patients, of which 15 were kidney transplants (two of which received a second kidney graft) and 29 were simultaneous pancreas-kidney transplants. All patients received grafts from cadaver donors. Azathioprine, cyclosporine, and corticoids were used as immunosuppressants in the majority of patients. Thirteen patients (2 kidney transplants and 11 simultaneous pancreas-kidney transplants) received tacrolimus, and fifteen (4 kidney transplants and 11 simultaneous pancreas-kidney transplants) received mycophenolate. In the simultaneous pancreas-kidney transplant group, induction with antibodies was used with OKT3 up to 1995, and with ATGAM from 1996 to 1998; recently, antiCD25 (Simulect) was used in two patients. For the statistical analyses, the chi-square test was used for qualitative variables, and the Student’s t test for quantitative variables. The Kaplan-Meier method was used to calculate actuarial survival, and the Log Rank test to compare survival between the two groups.
RESULTS
In demographic terms, no significant differences were observed as regards recipient age in the simultaneous pancreas-kidney transplant group (37.8 ⫾ 5.6 years) when compared with the kidney transplant group (41.8 ⫾ 9.4 years). The same occurred with gender (22 males and 7 females in the simultaneous pancreas-kidney transplant group, 10 males and 5 females in the kidney transplant group) and with the local extraction rate. However, a difference was
found (P ⫽ .02) in donor age, which was significantly lower in the simultaneous pancreas-kidney transplant group (24.9 ⫾ 10.8 years) when compared with the kidney transplant group (38.5 ⫾ 17 years). Hospital stays were significantly longer in the simultaneous pancreas-kidney transplant group (48.6 ⫾ 34.6 days) than in the kidney transplant group (18 ⫾ 11 days) (P ⬍ .01). This coincides with other published studies.6,7 The simultaneous pancreas-kidney transplant group underwent fewer cold ischemia hours (16.4 ⫾ 6.1 hours) than the kidney transplant group (22 ⫾ 8.8 hours; P ⬍ .02). The HLA-DR mismatch was significantly greater in simultaneous pancreas-kidney transplants (P ⫽ .001), with no differences observed in the percentage of reactivity to the panel, nor in HLA-A and HLA-B. The percentage of rejection in simultaneous pancreaskidney transplants was 20.6%, compared with 40% in kidney transplants (n.s.). There were no differences between both groups in plasmatic creatinine 3, 6, 12, and 24 months after transplant. Two years after transplant, kidney graft survival rate in kidney transplants was 73% and 81% in the simultaneous pancreas-kidney transplant group (P ⬍ .05). The causes of graft loss in kidney transplants were two thrombosis, one chronic rejection, and one due to cyclosporine toxicity. In the simultaneous pancreas-kidney transplant group, there was one due to chronic nephropathy, one to acute rejection, and one to thrombosis. Pancreas graft survival 2 years after transplant was 75%. Causes of loss were due in three cases to pancreatitis and in one to a thrombosis of the graft. Complications in the simultaneous pancreas-kidney transplant group were one ureteral stenosis, two urethral stenosis, two bladder fistulas, repeated pancreatitis in two patients (in whom pancreatic exocrine drainage was reconverted from bladder drainage to enteric drainage), and two duodenal segment leak. Patient survival in kidney transplants was 86% and 92% in simultaneous pancreaskidney transplants (P ⫽ .07). Causes of death in the kidney From the Nephrology, Surgery and Urology Sections, Reina Sofia Hospital, Co´rdoba, Spain. Address reprint requests to R. Perez, MD, Reina Sofia Hospital, Nephrology, Surgery and Urology Section, Avda Menendez Pidal s/n, 14004 Cordoba, Spain.
0041-1345/01/$–see front matter PII S0041-1345(01)02412-5
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
3494
Transplantation Proceedings, 33, 3494–3495 (2001)
PANCREAS-KIDNEY TRANSPLANT
transplant group were: one due to sepsis, one to acute myocardial infarction, and one to malignancy; and in simultaneous pancreas-kidney transplants, one due to sepsis.
3495
group, as a large part of them were transplanted more recently than the kidney transplants. REFERENCES
DISCUSSION
Type I diabetes mellitus patients who receive a simultaneous pancreas-kidney transplant show acute rejection, kidney graft function, and patient survival rates that are comparable with those of diabetic patients receiving kidney transplants. However, morbidity is greater in the simultaneous pancreas-kidney transplant group, as are complications, particularly in the first posttransplant year, which is reflected by longer hospital stays. This has been observed in previous series. Graft survival is significantly greater in the simultaneous pancreas-kidney transplant group than in the kidney transplant group, probably due to the new immunosuppression used in the majority of the patients in this
1. Nathan DM, Fogel H, Norman D, et al: Transplantation 52:85, 1991 2. Scheider A, Meyer-Schwickerath E, Nusser J, et al: Diabetologia 34 (Suppl 1):S95, 1991 3. Konigssrainer A, Miller K, Steurer W, et al: Diabetologia 34 (Suppl 1):S86, 1991 4. Fioretto P, Steffes MW, Sutherland DE, et al: N Engl J Med 339:69, 1998 5. Navarro X, Sutherland DE, Kennedy WR: Ann Neurol 42:727, 1997 6. Sollinger HW, Odorico JS, et al: Ann Surg 228:284, 1998 7. Cheung AHS, Sutherland DER, Gilligham KJ, et al: Kidney Int 41:924, 1992 8. Sutherland DER, Gruessner RWG, Gores PF: Transplant Rev 8:185, 1994