The Impact of Method on Kidney Graft and Patient Survival in Kidney-Pancreas Transplantations for Type I Diabetes Mellitus

Transcription

1 It Surg 2015;100: DOI: /INTSURG-D The Impact of Method o Kidey Graft ad Patiet Survival i Kidey-Pacreas Trasplatatios for Type I Diabetes Mellitus Ayha Dicka 1, Ibrahim Aliosmaoglu 1, Huseyi Kocak 2, Ayha Mesci 1, Hasa Altubas 3, Aliha Gurka 1 1 Departmet of Geeral Surgery, Medical Faculty, Akdeiz Uiversity, Atalya, Turkey 2 Departmet of Nephrology, Medical Faculty, Akdeiz Uiversity, Atalya, Turkey 3 Departmet of Edocriology, Medical Faculty, Akdeiz Uiversity, Atalya, Turkey Patiets who develop ed-stage real disease (ESRD) associated with Type I Diabetes Mellitus may receive kidey aloe (KA) trasplatatio, simultaeous pacreas-kidey (SPK) trasplatatio, or a pacreas after kidey (PAK) trasplatatio. The goal of this study is to examie the log-term impact of pacreas trasplatatio o kidey graft ad patiet survival rates. A total of 85 trasplatatio cases, cosistig of 30 that received livig door KA, 21 that received SPK, ad 34 that received PAK, from at Akdeiz Uiversity Orga Trasplatatio Istitute were retrospectively screeed. There was a graft loss i 4 cases from the KA group, ad i 1 case from each of the SPK ad PAK groups. The five-year kidey graft survival rates were 86.7% i KA, 95.2% i SPK, ad 97.1% i PAK. There was a sigle patiet loss i both KA ad SPK. The kidey survival percetages were higher i SPK ad PAK groups compared to the KA group. Therefore, SPK should be the primary preferece i these patiets; however, for the cases that have a livig door, pacreas trasplatatio should be cosidered after kidey trasplatatio, or the patiets ca be followed-up o with close blood sugar cotrol. Key words: Kidey Pacreas Trasplatatio Kidey survival Patiet survival Correspodig author: Assist. Prof. Ibrahim Aliosmaoglu, Akdeiz Uiversity Medical Faculty, Departmet of Geeral Surgery, Dumlupıar Bulvari, 07058, Atalya. Tel.: þ ; Fax: þ ; ialiosma@gmail.com It Surg 2015;

2 DINCKAN KIDNEY-PANCREAS TRANSPLANTATIONS The discovery of isuli i 1921 eabled the trasitio from diabetic ketoacidosis ad diabetic coma to a icreasig umber of patiets with prologed life expectacies i the cliical course of diabetes mellitus (DM). However, with prologed lifetime, icreases i the eurological, ocular, ad real complicatios of DM have become evidet. With a 40% rate, DM is the leadig cause of edstage real disease (ESRD) i the Uited States. 1 I patiets with type I DM-related kidey failure, kidey trasplat is highly more preferable i terms of the egative effects of log-term dialysis o the patiet survival ad quality of life compared with the beefits of kidey trasplats. 2 I patiets who develop type I DM-related kidey failure, kideyaloe trasplatatio (KA) from a livig door or a cadaver, simultaeous pacreas-kidey trasplatatio (SPK), or pacreas-after-kidey trasplatatio (PAK) are amog the trasplatatio alteratives. The 10-year life expectacy i patiets receivig hemodialysis for ESRD, ad i those udergoig livig door or a cadaveric real trasplatatio, was reported to be 4.4, 32.9, ad 59.3% i the Uited States, respectively. 3 Similarly, while the average life expectacy for diabetes patiets waitig for kidey trasplatatio was 8 years, the average life expectacy after kidey trasplatatio was determied to be 22 years. 2 Whe pacreas trasplatatio is added to kidey trasplatatio, prologed kidey ad patiet survival rates ca be attaied alog with other beefits, such as protectio from the secodary effects of diabetes ad a icrease i patiets quality of life. While the 4-year mortality rate i the selected dialysis patiets o the waitlist for pacreas-kidey was 40%, it was 10% i patiets who received SPK trasplatatio. 4 The goal of this study is to compare the impact of the KA, SPK, ad PAK trasplatatio methods o kidey graft ad patiet survival rates i patiets with ESRD associated with type I diabetes. Patiets ad Methods A total of 85 patiets who uderwet type I DMrelated kidey ad pacreas-kidey trasplatatio at the Akdeiz Uiversity Orga Trasplatatio Istitute betwee February 2003 ad Jue 2010 were icluded i this study. Patiets were divided ito three groups: KA, SPK, ad PAK. The door ad recipiet demographics were collected through retrospective screeig of the medical records (Table 1). SPK ad PAK patiets were give atithymocite globuli (ATG), 2.5 mg/kg/day, as iductio Table 1 Demographics features of patiets KA SPK PAK Age, y 33.4 (22 48) 33.6 (22 49) 32.0 (21 46) Geder, M:F 22:8 13:8 25:9 Diabetes 19.0 (3.9) 19.5 (3.0) 20.3 (4.0) duratio, y Dialysis 24.2 (23.7) 24.3 (15.7) 17.6 (11.2) duratio, mo Dialysis type (%) (%) (%) Preemptive 6 (20.0) 1 (4.7) 4 (11.8) Hemodialysis 16 (53.3) 18 (85.7) 21 (61.8) Peritoeal 8 (26.7) 2 (9.5) 9 (25.5) dialysis HLA MM 3.2 (1.5); (0 6) 3.2 (0.8); (2 5) 3.2 (1.1); (0 6) Kidey door Age 44.8 (27 72) 29.0 (13 49) 42.5 (22 71) Sex (M:F) 16:14 8:13 18:16 BMI, kg/m (3.1) 20.5 (1.4) 22.1 (2.0) Door type Livig Cadaver Follow-up duratio, mo 39.3 (27.1) 66.0 (24.1) 53.8 (29.2) BMI, body mass idex. therapy durig the early postoperative stage (days 5 through 14). Followig the iductio therapy, tacrolimus (0.15 mg/kg/day), 2 g/day double dose of mycopheolate mofetil (MMF), ad steroid protocol were applied. I the live door KA cases, there were patiets who used 6 to 8 mg/kg/day of cyclosporie i additio to the same protocol. For ifectio prophylaxis i the early postoperative period, 13.5 g/day of tazoci ad 200 mg/day of flucoazole were give to SPK ad PAK patiets, ad 1 g/sigle dose of 3rd geeratio cephalospori was give to KA patiets. Afterward, all patiets were admiistered with oral valgaciclovir ad cotrimoxazole treatmet for 6 moths. Iliac vessels were used for vascular aastomoses i all patiets. While low-molecular-weight hepari was used for thrombosis prophylaxis i the early postoperative period; 100 mg/day of aspiri was prescribed after the discharge. Acute ad chroic rejectio diagoses were made based o kidey biopsy i all patiets. 138 It Surg 2015;100

3 KIDNEY-PANCREAS TRANSPLANTATIONS DINCKAN Statistical Aalysis Statistical aalysis was coducted usig computer software (SPSS versio 15.0; SPSS Ic., Chicago, IL). Numeric, ordial, ad categorical variables are expressed as mea (stadard deviatio), media (miimum-maximum), ad (%), respectively. Studet s t-test ad the Ma-Whitey U test were used for aalysis of variables with ormal ad abormal distributio, respectively. The v 2 test was used for categorical variables. Tests of ormalcy were coducted usig the Kolmogorov Smirov test. All hypotheses were two-sided ad the alpha level of sigificace was set at Results Of all the cases, 30 (35.2%) were i the KA group, 21 (24.8%) i the SPK group, ad 34 (40%) were i the PAK group. age was 33.4 (22 48), 33.6 (22 49), ad 32.0 (21 46) years, respectively. There were 22 (73.3%) males ad 8 (26.7%) females i the KA group, 13 (61.9%) males ad 8 (38.1%) females i the SPK group, ad 25 (73.5%) males ad 9 (26.5%) females i the PAK group. Mea (SD) duratio of diabetes was 19.9 (3.9) years i KA patiets, 19.5 (3.0) years i SPK patiets, ad 20.3 (4.0) years i PAK patiets. door ages i the groups were 44.8 (27 72), 29.0 (13 49), 42.5 (22 72) years, respectively. Iliac vessels were used for all arterial ad veous aastomoses, except for 1 patiet i the PAK group with pacreatic veous draiage ito the portal system. The exocrie draiage was doe as bladder exocrie draiage i 7 ad as eteric exocrie draiage i 14 SPK patiets, as bladder exocrie draiage i 6 ad as eteric aastomosis i 28 PAK patiets. All patiets received low-molecular-weight hepari for postoperative hepariizatio. Oe PAK case developed real artery thrombosis postoperatively that was corrected with recostructio. Thrombosis was observed i the vascular aastomoses of the pacreatic graft of 3 SPK ad 7 PAK patiets. Of these cases, the flow was reistated i oe of the PAK patiets as a result of early itervetio recostructio; however, graft pacreatectomy was performed i all of the other cases. The surgical ad systemic complicatios observed i all three groups are displayed i Table 2, ad Table 3 displays the applied iductio therapy ad maiteace immuosuppressio protocol. Postoperative legth of hospital stay was 7.6 (3.4) days i KA, 18.3 (8.9) days i SPK, ad 19.5 (9.7) days i the PAK groups. Table 2 Surgical ad systemic complicatios, (%) KA, (%) SPK, (%) PAK, (%) Bleedig 1 (3.3) 3 (14.3) 6 (17.6) Duodeal stump leakage 1 (2.9) Uriary ifectio 1 (3.3) 4 (19.0) 7 (20.6) Lug problems 3 (14.3) 2 (5.9) Itra-abdomial abscess 2 (9.5) 5 (14.7) CMV ifectio 2 (6.7) 6 (28.5) 7 (20.5) Real artery thrombosis 1 (2.9) Pacreas graft portal vei thrombosis 3 (14.3) 7 (20.5) CMV, Cytomegalovirus. The media follow-up duratio for all patiets was 55 moths. Acute kidey rejectio was observed at least oce i 9 KA patiets, 2 SPK patiets, ad 4 PAK patiets (Table 3). Whe the acute rejectio icideces were compared across groups, the differece betwee KA ad SPK (P ¼ 0.037), ad the differece betwee KA ad PAK (P ¼ 0.035) was statistically sigificat. A total of 5 KA patiets, 1 SPK patiet, ad 2 PAK patiets received pulse steroid treatmet, ad the other patiets were treated with ATG (2.5 mg/kg/day). At the ed of the 5-year follow-up, kidey loss occurred i 4 KA, 1 SPK, ad 1 PAK patiets, while the kidey graft survival rate was 86.7%, 95.2%, ad 97.1%, respectively, i the groups (P ¼ 0.25). The fact that kidey graft survival percetages were higher i SPK ad PAK patiets whe compared with KA patiets, but ot statistically sigificat, was thought to be due to Table 3 Immuosuppressio protocols ad rejectio attack KA, SPK, AK, Iductio therapy Noe Daclizumab Basiliximab ATG Immuosuppressio protocol TAC þ MMF CSA þ MMF TAC þ SRL þ MMF 4 CSA þ SRL þ MMF 2 CSA þ EVE þ MMF 2 Acute kidey rejectio attacks ATG, atithymocyte globuli; CSA, cyclospori; EVE, everolimus; MMF, mycopheolate mofetil; SRL, sirolimus; TAC, tacrolimus. It Surg 2015;

4 DINCKAN KIDNEY-PANCREAS TRANSPLANTATIONS the small umber of patiets. Oe patiet from each of the KA ad SPK groups had died by the ed of the 5-year follow-up. I both cases, the cause of death was cardiovascular problems. There was o patiet loss i the PAK group. The 5-year patiet survival rate was 96.7%, 95.2%, ad 100%, respectively, i all groups; there was o statistical differece betwee the groups (P ¼ 0.34). Discussio Addig pacreas trasplatatio to kidey trasplatatio i type I diabetes patiets should be evaluated by cosiderig the key poits regardig the prologed patiet ad kidey life expectacy, i additio to the secodary beefits like dimiished secodary effects of diabetes ad icreased quality of life. 5 Improved results ad lower rates of complicatios ad rejectios have bee reported i pacreas trasplatatio by meas of ew surgical techiques ad advaces i immuosuppressive therapy. 6 I additio to improvemets obtaied i europathy, early retiopathy, ad blood lipidcholesterol profiles, developmet of ephropathy i kidey trasplat ca also be preveted via strict cotrol of blood glucose levels i the log-term follow-ups postpacreas-trasplatatio. 7 However, i additio to these importat beefits of pacreas trasplatatio, may early period complicatios are observed. I our study, there were sigificatly less postoperative complicatios i KA whe compared with SPK ad PAK procedures (Table 2). We believe that because livig-door kidey aloe (LDKA) is plaed ad the patiets have a appoitmet system that they ca prepare for, the cold ischemia time is lower; moreover, because it is a easier surgical itervetio tha SPK ad PAK, postoperative complicatios are ecoutered less frequetly ad the kidey graft starts to fuctio quicker. Acute kidey rejectio attacks are kow to have a importat effect o patiet ad kidey survival rates. 8 I this study, acute rejectio attack icideces were highest i the KA group. This differece was statistically sigificat i compariso with the groups that received SPK ad PAK procedures. The reaso for this differece across groups with similar mea values of HLA-MM may be due to the effect of primarily usig ATG i the iductio therapy of patiets who have pacreas trasplatatio. Cosiderig the effect of acute rejectio attacks o kidey graft survival rate, we observed at least 1 acute rejectio attack i 5 of the 6 patiets who had kidey graft loss, ad the relatioship betwee the acute rejectio attacks ad the kidey graft loss was statistically sigificat (P, 0.001). Cosiderig the patiet survival rates, as a result of the retrospective aalysis, compared with kidey aloe trasplats, SPK has a 2% higher postoperative mortality rate i the first 90 days; ad SPK ad LDKA s 1-year mortality ratios were foud to be 5% to 2 to 3%. 9,10 I a study by Youg et al, the 1-year patiet survival rate i SPK, LDKA, ad DDKA (deceased-door kidey aloe) was 95%, 97%, ad 93%, while the survival of kidey graft was 93, 95, ad 89%, respectively. 11 I terms of 6- year patiet survival rates, this was more i favor of SPK tha LDKA (85%, 80%), while the kidey graft survival rates were foud to be equal (72%, 72%). Through a 10-year follow-up i a study by Morath et al SPK was foud to be better tha LDKA ad DDKA i terms of post-trasplat kidey survival. 12 While Kleiclauss et al did ot fid ay differece betwee LDKA ad PAK patiets regardig patiet ad kidey survival rates, they observed that HbA1c ad glomerular filtratio rate (GFR) to be better i PAK cases. 13 I a study by Sampaio et al o the compariso of LDKA ad PAK patiets, both patiet survival rate (75 versus 85%) ad kidey survival rate (62 versus 75%) were determied to be better i the PAK group at the ed of the 8-year follow-up. 14 I this study, kidey graft survival rates i KA, SPK, ad PSK groups were 86.7, 95.2, ad 97.1%, ad patiet survival rates were 96.7, 95.2, ad 100%, respectively. Our fidigs revealed better kidey graft survival rates i patiets with kideypacreas trasplatatio, with o sigificat differeces with respect to patiet survival rates betwee trasplatatio methods durig log-term followup. Coclusio Cosequetly, based o our fidigs as well as related literature cocerig log-term follow-ups, kidey-pacreas trasplatatio seems to be associated with better cliical results compared with LDKA, maily due to better glycemic cotrol ad more promiet reductio i cardiovascular risk, makig it more preferable i terms of early-period complicatios ad risks tha pacreas trasplatatio. This study shows that kidey survival rate was higher i SPK ad PAK groups compared with the KA group. However, there were o differeces observed i terms of patiet survival rates. Therefore, SPK should be the primary preferece i patiets with ESRD associated with type I DM; 140 It Surg 2015;100

5 KIDNEY-PANCREAS TRANSPLANTATIONS DINCKAN however, for cases that have a livig door, pacreas trasplatatio should be cosidered oly after kidey trasplatatio ad blood glucose levels have bee closely moitored via follow-up. Refereces 1. Odorico JS, Solliger HW. Techical ad immuosuppressive advaces i trasplatatio for isuli-depedet diabetes mellitus. World J Surg 2002;26(2): Wolfe RA, Ashby VB, Milford EL, Ojo AO, Etteger RE, Agodoa LY et al. Compariso of mortality i all patiets o dialysis, patiets o dialysis awaitig trasplatatio, ad recipiets of a first cadaveric trasplat. N Egl J Med 1999; 341(23): US Real Data System. USRDS 1999 Aual Data Report: Atlas of Ed-Stage Real Disease i the Uited States. Bethesda, MD: Natioal Istitutes of Health, Natioal Istitute of Diabetes ad Digestive ad Kidey Diseases, 1999, E.52, E.68, E Gruesser RW, Sutherlad DE, Gruesser AC. Mortality assessmet for pacreas trasplats. Am J Trasplat 2004; 4(12): Wisema AC. The role of kidey-pacreas trasplatatio i diabetic kidey disease. Curr Diab Rep 2010;10(5): Yakupoglu YK, Dicka A, Gurka A, Tucer M, Erdoga O, Altubas H et al. Kidey-Pacreas trasplatatio: sigleceter experiece at a uiversity hospital i Turkey. Trasplat Proc 2005;37(7): Smets YF, Westedorp RG, va der Pijl JW, de Charro FT, Rigers J, de Fijter JW et al. Effect of simultaeous pacreaskidey trasplatatio o mortality of patiets with type-1 diabetes mellitus ad ed-stage real failure. Lacet 1999; 353(9168): Ragel EB, Melarago CS, Gozalez AM, Lihares MM, de Sá JR, Salzedas A et al. Delayed kidey allograft fuctio after simultaeous pacreas-kidey trasplatatio. Trasplat Proc 2010;42(9): Gruesser AC, Sutherlad DE, Gruesser RW. Pacreas trasplatatio i the Uited States: a review. Curr Opi Orga Trasplat 2010;15(1): Martis L, Heriques AC, Dias L, Pedroso S, Almeida M, Satos J et al. Oe hudred eleve simultaeous pacreaskidey trasplatatio: 10-year experiece from a sigle ceter i Portugal. Trasplat Proc 2011;43(1): Youg BY, Gill J, Huag E, Takemoto SK, Aastasi B, Shah T et al. Livig door kidey versus simultaeous pacreas-kidey trasplat i type I diabetics: a aalysis of the OPTN/UNOS database. Cli J Am Soc Nephrol 2009;4(4): Morath C, Zeier M, Döhler B, Schmidt J, Nawroth PP, Opelz G. Metabolic cotrol improves log-term real allograft ad patiet survival i type 1 diabetes. J Am Soc Nephrol 2008;19(8): Kleiclauss F, Fauda M, Sutherlad DE, Kleiclauss C, Gruesser RW, Matas AJ et al. Pacreas after livig door kidey trasplats i diabetic patiets: impact o log-term kidey graft fuctio. Cli Trasplat 2009;23(4): Sampaio MS, Poommipait N, Cho YW, Shah T, Buapradist S. Trasplatatio with pacreas after livig door kidey vs. livig door kidey aloe i type 1 diabetes mellitus recipiets. Cli Trasplat 2010;24(6): It Surg 2015;