Influence of Simultaneous Pancreas and Preemptive Kidney Transplantation on Severity of Postoperative Complications T. Grochowiecki, Z. Gałazka, S. Frunze, S. Nazarewski, T. Jakimowicz, L. Paczek, M. Durlik, M. Lao, and J. Szmidt ABSTRACT Background. Simultaneous pancreas and preemptive kidney transplantation (SPpreKT) seems to be the optimal treatment for the patients with diabetes type 1 who are progressing to end-stage renal disease. On the other hand, surgical complications with a high rate of relaparatomy are a limiting factor in pancreas transplantation. Objective. Comparison of severity of surgical complications was performed between a group of preemptive (SPpreKT group) and nonpreemptive recipients of SPKT (SPKT group). Methods. Between 1988 and 2010, we performed 112 SPKTs including 25 preemptive recipients (22.3%). The SPKT Group included 87 recipients (77.7%). The severity of complications was classified according to a modified Clavien scale: grade I, no complication; grade II, drug therapy; grade IIIA, invasive intervention not requiring general anesthesia; grade IIIB, invasive intervention requiring general anesthesia; grade IVA, graft failure; and grade IVB, death. Results. Among the SPpreKT group, 64% of recipients were free from postoperative complications compared with 40.3% of the SPKT group (P ⬍ .01). Among the SPKT group, 52 recipients (59.7%) developed 58 postoperative complications, including 15 (17.3%) deaths due to graft pancreatitis (80%) or pancreatic fistula (20%). Among the SPpreKT group, 9 recipients developed 9 complications. None of the preemptively transplanted group subjects experienced a lethal complication. Among the SPpreKT group, the most severe complication was graft pancreatitis leading to graft removal in 2 recipients. Conclusions. Recipients of preemptive SPKT developed significantly fewer postoperative complications, especially deaths. However the rates of mild (II, IIIA) and moderate (IIIB) complications as well as graft failures (IVA) were similar to the nonpreemptive group.
L
iving-donor kidney transplantation and simultaneous pancreas and kidney transplantation (SPKT) are therapeutic transplant modalities that result in long-lasting survival of patients with diabetes type 1 and end-stage diabetic nephropathy.1,2 However, simultaneous pancreas and preemptive kidney transplantation (SPpreKT) seems to
be a better therapeutic option than SPKT in previously dialyzed recipients.2–5 SPpreKT was associated with a lower risk not only for mortality (adjusted risk ratio, 0.5) but also for kidney graft loss (adjusted risk ratio, 0.79) compared with SPKT after prior dialysis.5 Multivariant analysis of International Pancreas Transplant Registry/United Net-
From the Department of General, Vascular, and Transplant Surgery (T.G., Z.G., S.F., S.N., T.J., J.S.), Department of Immunology, Transplantology, and Internal Diseases (L.P.), and Department of Transplantation Medicine and Nephrology (M.D.), Warsaw Medical University, and Department of Gastrointestinal Surgery and Transplantology (M.L.), Central Clinical Hospital of Ministry of Foreign Affairs, Warsaw, Poland.
Address reprint requests to Tadeusz Grochowiecki, Department of General, Vascular, and Transplant Surgery, Medical University of Warsaw, 1a Banacha Street, 02-097 Warsaw, Poland. E-mail:
[email protected]
0041-1345/11/$–see front matter doi:10.1016/j.transproceed.2011.08.029
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Transplantation Proceedings, 43, 3102–3104 (2011)
SIMULTANEOUS PANCREAS AND PREEMPTIVE KIDNEY TRANSPLANTATION
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Table 1. Characteristics of Recipients
Age of recipient (y) Gender (male/female) Duration of diabetes (y) Total ischemia time of transplanted pancreas/kidney (min) Vascular anastomosis time of transplanted pancreas/kidney (min)
work for Organ Sharing data showed pretransplant dialysis to increase the relative risk of mortality by 1.22 for SPKT recipients. Moreover, each year on dialysis increased this relative risk by 8%.4 Surgical complications with a high rate of relaparatomy is a limiting factor in pancreas transplantation.6 It took 101 days after transplantation for SPKT recipients to equal the relative mortality risk of wait-listed SPKT type 1 diabetic transplant candidates.1 This observation indicated that postoperative complications after SPKT show a great impact on early recipient survival as well as on late results.7 In the present study, we compared the severity of surgical complications among recipients of SPpreKT versus simultaneous pancreas and nonpreemptive kidney transplantation (SPKT) group.
SPpreKT (n ⫽ 25)
SPKT (n ⫽ 87)
39 ⫾ 9 9/16 24 ⫾ 9 558 ⫾ 146/589 ⫾ 254 38 ⫾ 9/32 ⫾ 7
38 ⫾ 7 37/50 24 ⫾ 6 504 ⫾ 158/571 ⫾ 210 40 ⫾ 17/34 ⫾ 11
4-anastomosis technique.8 Among the SPKT group 24/87 recipients (27.6%) were prescribed daclizimab, cyclosporine, and mycophenolate mofetil versus 39/87 (44.8%) who received ATG, mycophenolate mofetil, tacrolimus, and steroids. In 24 (27.6%) of the segmental transplant recipients, immunosuppression consisted of ATG, azathioprine, cyclosporine, and steroids. There were no significant differences between the groups regarding recipient and donor ages, duration of diabetes, total ischemia time, and vascular anastamosis time for the pancreas and kidney (Table 1). We classified the severity of complications according to a Clavien scale adjusted for pancreas transplantation.9 The suffix “g” referred to graft pancreatectomy (Table 2). If the recipient developed ⬎1 complication, the complication of the higher grade was used for the recipient.
RESULTS MATERIALS AND METHODS From February 1988 to December 2010, we performed 112 SPKTs, including 25 (22.3%) SPpreKTs. These 25 recipients showed a mean serum creatinine value before operation of 4.21 ⫾ 1.56 mg/dL. Systemic-enteric drainage was used in all cases. All subjects but 1 (96%) received antithymocyte globulin (ATG), mycophenolate mofetil, tacrolimus, and steroids for immunosuppression. The 1 recipient who had a segmental pancreatic transplant was prescribed ATG, azathioprine, cyclosporine, and steroids. The nonpreemptive group of 87 recipients (SPKT group) included 69 (79.3%) with prior treatment with hemodialysis and 18 (20.7%) with peritoneal dialysis. The mean time of renal replacement therapy before spktx was 27 ⫾ 20 months. Among the 72.4% (63/87) whole pancreatic transplantations, 12 (19%) had portoenteric and 51 (81%) systemic-enteric drainage. Twenty-four recipients (27.6%) received segmental pancreatic transplant with a Table 2. Severity Grading of Postoperative Complications According to Clavien-Dindo Classification Modified for Pancreas Transplantation Grade of Complication Severity
I II III IIIA IIIB IV IVA IVB g [suffix]
Definition
No complication Pharmacological treatment Invasive intervention (radiologic, endoscopic, operative) Invasive intervention not requiring general anesthesia Invasive intervention requiring general anesthesia Life- or graft-threatening complication Failure of the graft Death Graftectomy
Comparison of the severity grading of postoperative complications for preemptive versus nonpreemptive recipients is shown in Table 3. Among the SPpreKT group, 64% of recipients were free from postoperative complications, compared with 40.3% SPKT recipients (P ⬍ .01). In the SPKT group, 52 recipients (59.7%) developed 58 postoperative complications with 3 subjects showing 2 complications. There were 15 (17.3%) deaths due to complications related to pancreatic grafts among the SPKT group. The main reason for grade IVB complications were graft pancreatitis (80%) or pancreatic fistula (20%) both of which led to multiorgan failure and subsequently death, despite 12 (80%) graft pancreatectomies (Table 4). Graft pancreatitis, pancreatic fistula, or pancreatic graft vessel thrombosis were the cause of graft failure in 38.5%, 7.7%, and 53.8% of cases, respectively. All grafts were removed (grade IVAg). Graft pancreatitis and pancreatic fistula were successfully treated operatively in 4 cases (grade IIIB). Four recipients treated conservatively showed resolution of graft pancreatitis with closure of the pancreatic graft fistula. Hemorrhage into the peritoneal cavity required 3 relapatotomies. In 2/16 cases (12.5%) pancreatic graft vessel thrombosis was sucTable 3. Comparison of Postoperative Complication Severity Grading Between SPpreKT and SPKT Recipients Grade
SPpreKT
SPKT
I II and IIIA IIIB IVA IVB
16 (64%) 3 (12%) 3 (12%) 3 (12%) 0
35 (40.3%) 7 (8%) 7 (8%) 23 (26.4%) 15 (17.3%)
*Fisher test.
P ⬍ .05* ns ns ns P ⬍ .05*
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GROCHOWIECKI, GALAZKA, FRUNZE ET AL Table 4. Surgical Complication of SPKT Recipients According to Severity Grading Classification
Grade
Graft Pancreatitis
Perigraft Fluid Collection
Pancreatic Fistula
Hemorrhage into Peritoneal Cavity
Graft Vessel Thrombosis
Total
II and IIIA III B IVA/IVAg IVB/IVBg Total
3 3 0/10 2/10 28
1 3 0 0 4
1 1 0/2 1/2 7
0 3 0 0 3
2 0 0/14 0 16
7 10 26 15 58
cessfully treated by intravenous heparin infusions. None of the preemptively transplanted recipients developed a lethal complication. In the SPpreKT group the most severe complication was graft pancreatitis leading to graft removal in 2 recipients (Table 5). Hemorrhage from the enteric anastomosis into the gastrointestinal tract required 3 relaparatomies. In this group, grade II and IIIA complications were due to 1 perigraft fluid collection, which was drained under ultrasonographic guidance, and 2 small vessel graft thromboses which resolved with intravenous heparin infusion.
multicenter study based on the same methodology should be undertaken to more effectively solve this problem. In conclusion, recipients of a simultaneously transplanted pancreas and a preemptive kidney transplant developed significantly fewer postoperative complications, especially lethal ones. However, the rates of mild (II, IIIA) and moderate (IIIB) complications, as well as graft failures (IVA), were similar between SPpreKT and SPKT groups in this limited experience. REFERENCES
DISCUSSION
It has been previously shown on long-term follow-up that SPpreKT recipients enjoy a lower mortality risk than those who undergo dialysis before transplantation.4,5 However, there has been little attention on the impact of preemptive transplantation on early posttransplant outcomes. To address this need, we adopted the Clavien-Dindo classification which has been used by numerous investigators.10 It dissected each complication type in relation to its severity based on an assessment of the treatment. We demonstrated that preemptive transplant recipients developed fewer postoperative complications than predialyzed SPKT recipients, particularly lethal courses. Graft pancreatitis and pancreatic graft fistula caused multiorgan failure leading to death despite pancreatic graft removal. Graft vessel thrombosis was the reason for failure and subsequent graft removal only among the SPKT group. It might be speculated that graft pancreatitis and graft vessel thrombosis showed more severe clinical manifestations among nonpreemptive recipients. The limitations of this study included its retrospective nature as well as various surgical techniques and immunosuppressive protocols among the SPKT recipients, rendering this group less consistent than the SPpreKT cases, which may be the reason that no difference were observed among mild and moderate complications between the groups. A
1. Ojo AO, Meier-Kriesche HU, Hanson JA, et al: The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. Transplantation 71:82, 2001 2. Wiseman A: The role of kidney-pancreas transplantation in diabetic kidney disease. Curr Diab Rep 10:385, 2010 3. Grochowiecki T, Szmidt J, Gałazka Z, et al: Comparison of 1-year patient and graft survival rates between preemptive and dialysed simultaneous pancreas and kidney transplant recipients. Transplant Proc 38:261, 2006 4. Ranga KV, Desai CS, Gruessner AC, et al: Improved long term survival in simultaneous pancreas kidney transplant following preemptive transplantation. Rev Diabet Stud 8:1, 2011 5. Becker BN, Rush SH, Dykstra DM, et al: Preemptive transplantation for patients with diabetes-related kidney disease. Arch Intern Med 166:44, 2006 6. Fellmer PT, Pascher A, Kahl A, et al: Influence of donor- and recipient-specific factors on the postoperative course after combined pancreas-kidney transplantation. Langenbecks Arch Surg 395:19, 2010 7. Weiss AS, Smits G, Wiseman AC, et al: Twelve-month pancreas graft function significantly influences survival following simultaneous pancreas-kidney transplantation. Clin J Am Soc Nephrol 4:988, 2009 8. Szmidt J, Lao M, Grochowiecki T, et al: Pancreas transplantation: four vascular anastomoses Transplant Proc 28:3511, 1996 9. Dindo D, Demartines N, Clavien PA, et al: Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205, 2004 10. Clavien PA, Barkun J, Oliviera ML, et al: The ClavienDindo classification of surgical complications. Ann Surg 250:187, 2009
Table 5. Surgical Complication of Spprektx Recipients According to Severity Grading Classification Grade
Graft Pancreatitis
Perigraft Fluid Collection
Hemorrhage from Enteric Anastomosis into Gastrointestinal Tract
Graft Vessel Thrombosis
Total
II and IIIA III B IVA/IVAg IVB/IVBg Total
0 0 1/2 0 3
1 0 0 0 1
0 3 0 0 3
2 0 0 0 2
3 3 3 0 9