Warm ischemia time and elevated serum uric acid are associated with metabolic syndrome after liver transplantation with donation after cardiac death
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摘要
AIM To describe the prevalence of posttransplant metabolic syndrome(PTMS) after donation after cardiac death(DCD) liver transplantation(LT) and the pre-and postoperative risk factors.METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre-and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-Ⅲ criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147(13.6%). Recipient's body mass index(P = 0.024), warm ischemia time(WIT)(P = 0.045), and posttransplant hyperuricemia(P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients(P < 0.001). After the 1 s t mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.
AIM To describe the prevalence of posttransplant metabolic syndrome(PTMS) after donation after cardiac death(DCD) liver transplantation(LT) and the pre-and postoperative risk factors.METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre-and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-Ⅲ criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147(13.6%). Recipient's body mass index(P = 0.024), warm ischemia time(WIT)(P = 0.045), and posttransplant hyperuricemia(P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients(P < 0.001). After the 1 s t mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.
AIM To describe the prevalence of posttransplant metabolic syndrome(PTMS) after donation after cardiac death(DCD) liver transplantation(LT) and the pre-and postoperative risk factors.METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre-and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-Ⅲ criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147(13.6%). Recipient's body mass index(P = 0.024), warm ischemia time(WIT)(P = 0.045), and posttransplant hyperuricemia(P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients(P < 0.001). After the 1 s t mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.
引文
1 Doyle MB,Collins K,Vachharajani N,Lowell JA,Shenoy S,Nalbantoglu I,Byrnes K,Garonzik-Wang J,Wellen J,Lin Y,Chapman WC.Outcomes Using Grafts from Donors after Cardiac Death.J Am Coll Surg 2015;221:142-152[PMID:26095563 DOI:10.1016/j.jamcollsurg.2015.03.053]
2 O’Neill S,Roebuck A,Khoo E,Wigmore SJ,Harrison EM.Ameta-analysis and meta-regression of outcomes including biliary complications in donation after cardiac death liver transplantation.Transpl Int 2014;27:1159-1174[PMID:25052036 DOI:10.1111/tri.12403]
3 Khorsandi SE,Giorgakis E,Vilca-Melendez H,O’Grady J,Heneghan M,Aluvihare V,Suddle A,Agarwal K,Menon K,Prachalias A,Srinivasan P,Rela M,Jassem W,Heaton N.Developing a donation after cardiac death risk index for adult and pediatric liver transplantation.World J Transplant 2017;7:203-212[PMID:28698837 DOI:10.5500/wjt.v7.i3.203]
4 Satapathy SK,Charlton MR.Posttransplant metabolic syndrome:new evidence of an epidemic and recommendations for management.Liver Transpl 2011;17:1-6[PMID:21254337 DOI:10.1002/lt.22222]
5 Lunati ME,Grancini V,Agnelli F,Gatti S,Masserini B,Zimbalatti D,Pugliese G,Rossi G,Donato MF,Colombo M,Beck-Peccoz P,Orsi E.Metabolic syndrome after liver transplantation:short-term prevalence and pre-and post-operative risk factors.Dig Liver Dis 2013;45:833-839[PMID:23816695 DOI:10.1016/j.dld.2013.03.009]
6 Tan HL,Lim KB,Iyer SG,Chang SK,Madhavan K,Kow AW.Metabolic syndrome after a liver transplantation in an Asian population.HPB(Oxford)2015;17:713-722[PMID:26172138DOI:10.1111/hpb.12435]
7 Morrissey PE,Monaco AP.Donation after circulatory death:current practices,ongoing challenges,and potential improvements.Transplantation 2014;97:258-264[PMID:24492420 DOI:10.1097/01.TP.0000437178.48174.db]
8 Liu YY,Li CP,Huai MS,Fu XM,Cui Z,Fan LL,Zhang S,Liu Y,Ma J,Li G,Shen ZY.Comprehensive comparison of three different immunosuppressive regimens for liver transplant patients with hepatocellular carcinoma:steroid-free immunosuppression,induction immunosuppression and standard immunosuppression.PLo S One 2015;10:e0120939[PMID:25816221 DOI:10.1371/journal.pone.0120939]
9 Grundy SM,Cleeman JI,Daniels SR,Donato KA,Eckel RH,Franklin BA,Gordon DJ,Krauss RM,Savage PJ,Smith SCJr,Spertus JA,Costa F;American Heart Association;National Heart,Lung,and Blood Institute.Diagnosis and management of the metabolic syndrome:an American Heart Association/National Heart,Lung,and Blood Institute Scientific Statement.Circulation 2005;112:2735-2752[PMID:16157765 DOI:10.1161/CIRCULATIONAHA.105.169404]
10 WHO Expert Consultation.Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies.Lancet 2004;363:157-163[PMID:14726171 DOI:10.1016/S0140-6736(03)15268-3]
11 Laryea M,Watt KD,Molinari M,Walsh MJ,McAlister VC,Marotta PJ,Nashan B,Peltekian KM.Metabolic syndrome in liver transplant recipients:prevalence and association with major vascular events.Liver Transpl 2007;13:1109-1114[PMID:17663411 DOI:10.1002/lt.21126]
12 Bianchi G,Marchesini G,Marzocchi R,Pinna AD,Zoli M.Metabolic syndrome in liver transplantation:relation to etiology and immunosuppression.Liver Transpl 2008;14:1648-1654[PMID:18975273 DOI:10.1002/lt.21588]
13 Shintani Y,Fujie H,Miyoshi H,Tsutsumi T,Tsukamoto K,Kimura S,Moriya K,Koike K.Hepatitis C virus infection and diabetes:direct involvement of the virus in the development of insulin resistance.Gastroenterology 2004;126:840-848[PMID:14988838 DOI:10.1053/j.gastro.2003.11.056]
14 Gitto S,Villa E.Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant.Int J Mol Sci 2016;17:490[PMID:27049380 DOI:10.3390/ijms17040490]
15 Laish I,Braun M,Mor E,Sulkes J,Harif Y,Ben Ari Z.Metabolic syndrome in liver transplant recipients:prevalence,risk factors,and association with cardiovascular events.Liver Transpl 2011;17:15-22[PMID:21254340 DOI:10.1002/lt.22198]
16 Pagadala M,Dasarathy S,Eghtesad B,McCullough AJ.Posttransplant metabolic syndrome:an epidemic waiting to happen.Liver Transpl 2009;15:1662-1670[PMID:19938136DOI:10.1002/lt.21952]
17 Anastácio LR,Diniz KG,Ribeiro HS,Ferreira LG,Lima AS,Correia MI,Vilela EG.Prospective evaluation of metabolic syndrome and its components among long-term liver recipients.Liver Int 2014;34:1094-1101[PMID:24517561 DOI:10.1111/liv.12495]
18 Liu C,Wang X,Chen Z,Zhang L,Wu Y,Zhang Y.Hepatic ischemia-reperfusion induces insulin resistance via downregulation during the early steps in insulin signaling in rats.Transplant Proc 2008;40:3330-3334[PMID:19100383 DOI:10.1016/j.transproceed.2008.07.143]
19 Hartog H,May CJ,Corbett C,Phillips A,Tomlinson JW,Mergental H,Isaac J,Bramhall S,Mirza DF,Muiesan P,Perera MT.Early occurrence of new-onset diabetes after transplantation is related to type of liver graft and warm ischaemic injury.Liver Int2015;35:1739-1747[PMID:25349066 DOI:10.1111/liv.12706]
20 Perera MT,Higdon R,Richards DA,Silva MA,Murphy N,Kolker E,Mirza DF.Biomarker differences between cadaveric grafts used in human orthotopic liver transplantation as identified by coulometric electrochemical array detection(CEAD)metabolomics.OMICS 2014;18:767-777[PMID:25353146 DOI:10.1089/omi.2014.0094]
21 Anastácio LR,de Oliveira MC,Diniz KG,Ferreira AM,Lima AS,Correia MI,Vilela EG.Adipokines,inflammatory mediators,and insulin-resistance parameters may not be good markers of metabolic syndrome after liver transplant.Nutrition 2016;32:921-927[PMID:27189907 DOI:10.1016/j.nut.2015.12.038]
22 Neal DA,Tom BD,Gimson AE,Gibbs P,Alexander GJ.Hyperuricemia,gout,and renal function after liver transplantation.Transplantation 2001;72:1689-1691[PMID:11726834 DOI:10.1097/00007890-200111270-00021]
23 Stamp L,Searle M,O’Donnell J,Chapman P.Gout in solid organ transplantation:a challenging clinical problem.Drugs 2005;65:2593-2611[PMID:16392875 DOI:10.2165/00003495-200565180-00004]
24 Layton ME,Wood JG,Yan ZY,Forster J.Ischemia/reperfusion alters uric acid and ascorbic acid levels in liver.J Surg Res 1996;64:1-5[PMID:8806465 DOI:10.1006/jsre.1996.0297]
25 Nakagawa T,Tuttle KR,Short RA,Johnson RJ.Hypothesis:fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome.Nat Clin Pract Nephrol 2005;1:80-86[PMID:16932373 DOI:10.1038/ncpneph0019]
26 Leithead JA,Tariciotti L,Gunson B,Holt A,Isaac J,Mirza DF,Bramhall S,Ferguson JW,Muiesan P.Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury.Am J Transplant 2012;12:965-975[PMID:22226302 DOI:10.1111/j.1600-6143.2011.03894.x]
27 Rosser BG,Gores GJ.Liver cell necrosis:cellular mechanisms and clinical implications.Gastroenterology 1995;108:252-275[PMID:7806049 DOI:10.1016/0016-5085(95)90032-2]
28 Fernández L,Heredia N,Grande L,Gómez G,Rimola A,Marco A,GelpíE,Roselló-Catafau J,Peralta C.Preconditioning protects liver and lung damage in rat liver transplantation:role of xanthine/xanthine oxidase.Hepatology2002;36:562-572[PMID:12198648DOI:10.1053/jhep.2002.34616]
29 Kim KM,Kim SS,Yun S,Lee MS,Han DJ,Yang WS,Park JS,Park SK.Uric acid contributes to glomerular filtration rate deterioration in renal transplantation.Nephron Clin Pract 2011;118:c136-c142[PMID:21150221 DOI:10.1159/000320616]
30 Choi HK,Ford ES.Prevalence of the metabolic syndrome in individuals with hyperuricemia.Am J Med 2007;120:442-447[PMID:17466656 DOI:10.1016/j.amjmed.2006.06.040]
31 Li Q,Lu J,Cao X,Shi TT,Feng JP,Yang JK.An Increase in Normal SUA Level Within the Normal Range Predicts Risk of Metabolic Syndrome,Especially in Women:A Cross-Sectional Study.Horm Metab Res 2017;49:338-342[PMID:28351090DOI:10.1055/s-0042-117010]
32 Liu Z,Que S,Zhou L,Zheng S.Dose-response Relationship of Serum Uric Acid with Metabolic Syndrome and Non-alcoholic Fatty Liver Disease Incidence:A Meta-analysis of Prospective Studies.Sci Rep 2015;5:14325[PMID:26395162 DOI:10.1038/srep14325]
2 O’Neill S,Roebuck A,Khoo E,Wigmore SJ,Harrison EM.Ameta-analysis and meta-regression of outcomes including biliary complications in donation after cardiac death liver transplantation.Transpl Int 2014;27:1159-1174[PMID:25052036 DOI:10.1111/tri.12403]
3 Khorsandi SE,Giorgakis E,Vilca-Melendez H,O’Grady J,Heneghan M,Aluvihare V,Suddle A,Agarwal K,Menon K,Prachalias A,Srinivasan P,Rela M,Jassem W,Heaton N.Developing a donation after cardiac death risk index for adult and pediatric liver transplantation.World J Transplant 2017;7:203-212[PMID:28698837 DOI:10.5500/wjt.v7.i3.203]
4 Satapathy SK,Charlton MR.Posttransplant metabolic syndrome:new evidence of an epidemic and recommendations for management.Liver Transpl 2011;17:1-6[PMID:21254337 DOI:10.1002/lt.22222]
5 Lunati ME,Grancini V,Agnelli F,Gatti S,Masserini B,Zimbalatti D,Pugliese G,Rossi G,Donato MF,Colombo M,Beck-Peccoz P,Orsi E.Metabolic syndrome after liver transplantation:short-term prevalence and pre-and post-operative risk factors.Dig Liver Dis 2013;45:833-839[PMID:23816695 DOI:10.1016/j.dld.2013.03.009]
6 Tan HL,Lim KB,Iyer SG,Chang SK,Madhavan K,Kow AW.Metabolic syndrome after a liver transplantation in an Asian population.HPB(Oxford)2015;17:713-722[PMID:26172138DOI:10.1111/hpb.12435]
7 Morrissey PE,Monaco AP.Donation after circulatory death:current practices,ongoing challenges,and potential improvements.Transplantation 2014;97:258-264[PMID:24492420 DOI:10.1097/01.TP.0000437178.48174.db]
8 Liu YY,Li CP,Huai MS,Fu XM,Cui Z,Fan LL,Zhang S,Liu Y,Ma J,Li G,Shen ZY.Comprehensive comparison of three different immunosuppressive regimens for liver transplant patients with hepatocellular carcinoma:steroid-free immunosuppression,induction immunosuppression and standard immunosuppression.PLo S One 2015;10:e0120939[PMID:25816221 DOI:10.1371/journal.pone.0120939]
9 Grundy SM,Cleeman JI,Daniels SR,Donato KA,Eckel RH,Franklin BA,Gordon DJ,Krauss RM,Savage PJ,Smith SCJr,Spertus JA,Costa F;American Heart Association;National Heart,Lung,and Blood Institute.Diagnosis and management of the metabolic syndrome:an American Heart Association/National Heart,Lung,and Blood Institute Scientific Statement.Circulation 2005;112:2735-2752[PMID:16157765 DOI:10.1161/CIRCULATIONAHA.105.169404]
10 WHO Expert Consultation.Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies.Lancet 2004;363:157-163[PMID:14726171 DOI:10.1016/S0140-6736(03)15268-3]
11 Laryea M,Watt KD,Molinari M,Walsh MJ,McAlister VC,Marotta PJ,Nashan B,Peltekian KM.Metabolic syndrome in liver transplant recipients:prevalence and association with major vascular events.Liver Transpl 2007;13:1109-1114[PMID:17663411 DOI:10.1002/lt.21126]
12 Bianchi G,Marchesini G,Marzocchi R,Pinna AD,Zoli M.Metabolic syndrome in liver transplantation:relation to etiology and immunosuppression.Liver Transpl 2008;14:1648-1654[PMID:18975273 DOI:10.1002/lt.21588]
13 Shintani Y,Fujie H,Miyoshi H,Tsutsumi T,Tsukamoto K,Kimura S,Moriya K,Koike K.Hepatitis C virus infection and diabetes:direct involvement of the virus in the development of insulin resistance.Gastroenterology 2004;126:840-848[PMID:14988838 DOI:10.1053/j.gastro.2003.11.056]
14 Gitto S,Villa E.Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant.Int J Mol Sci 2016;17:490[PMID:27049380 DOI:10.3390/ijms17040490]
15 Laish I,Braun M,Mor E,Sulkes J,Harif Y,Ben Ari Z.Metabolic syndrome in liver transplant recipients:prevalence,risk factors,and association with cardiovascular events.Liver Transpl 2011;17:15-22[PMID:21254340 DOI:10.1002/lt.22198]
16 Pagadala M,Dasarathy S,Eghtesad B,McCullough AJ.Posttransplant metabolic syndrome:an epidemic waiting to happen.Liver Transpl 2009;15:1662-1670[PMID:19938136DOI:10.1002/lt.21952]
17 Anastácio LR,Diniz KG,Ribeiro HS,Ferreira LG,Lima AS,Correia MI,Vilela EG.Prospective evaluation of metabolic syndrome and its components among long-term liver recipients.Liver Int 2014;34:1094-1101[PMID:24517561 DOI:10.1111/liv.12495]
18 Liu C,Wang X,Chen Z,Zhang L,Wu Y,Zhang Y.Hepatic ischemia-reperfusion induces insulin resistance via downregulation during the early steps in insulin signaling in rats.Transplant Proc 2008;40:3330-3334[PMID:19100383 DOI:10.1016/j.transproceed.2008.07.143]
19 Hartog H,May CJ,Corbett C,Phillips A,Tomlinson JW,Mergental H,Isaac J,Bramhall S,Mirza DF,Muiesan P,Perera MT.Early occurrence of new-onset diabetes after transplantation is related to type of liver graft and warm ischaemic injury.Liver Int2015;35:1739-1747[PMID:25349066 DOI:10.1111/liv.12706]
20 Perera MT,Higdon R,Richards DA,Silva MA,Murphy N,Kolker E,Mirza DF.Biomarker differences between cadaveric grafts used in human orthotopic liver transplantation as identified by coulometric electrochemical array detection(CEAD)metabolomics.OMICS 2014;18:767-777[PMID:25353146 DOI:10.1089/omi.2014.0094]
21 Anastácio LR,de Oliveira MC,Diniz KG,Ferreira AM,Lima AS,Correia MI,Vilela EG.Adipokines,inflammatory mediators,and insulin-resistance parameters may not be good markers of metabolic syndrome after liver transplant.Nutrition 2016;32:921-927[PMID:27189907 DOI:10.1016/j.nut.2015.12.038]
22 Neal DA,Tom BD,Gimson AE,Gibbs P,Alexander GJ.Hyperuricemia,gout,and renal function after liver transplantation.Transplantation 2001;72:1689-1691[PMID:11726834 DOI:10.1097/00007890-200111270-00021]
23 Stamp L,Searle M,O’Donnell J,Chapman P.Gout in solid organ transplantation:a challenging clinical problem.Drugs 2005;65:2593-2611[PMID:16392875 DOI:10.2165/00003495-200565180-00004]
24 Layton ME,Wood JG,Yan ZY,Forster J.Ischemia/reperfusion alters uric acid and ascorbic acid levels in liver.J Surg Res 1996;64:1-5[PMID:8806465 DOI:10.1006/jsre.1996.0297]
25 Nakagawa T,Tuttle KR,Short RA,Johnson RJ.Hypothesis:fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome.Nat Clin Pract Nephrol 2005;1:80-86[PMID:16932373 DOI:10.1038/ncpneph0019]
26 Leithead JA,Tariciotti L,Gunson B,Holt A,Isaac J,Mirza DF,Bramhall S,Ferguson JW,Muiesan P.Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury.Am J Transplant 2012;12:965-975[PMID:22226302 DOI:10.1111/j.1600-6143.2011.03894.x]
27 Rosser BG,Gores GJ.Liver cell necrosis:cellular mechanisms and clinical implications.Gastroenterology 1995;108:252-275[PMID:7806049 DOI:10.1016/0016-5085(95)90032-2]
28 Fernández L,Heredia N,Grande L,Gómez G,Rimola A,Marco A,GelpíE,Roselló-Catafau J,Peralta C.Preconditioning protects liver and lung damage in rat liver transplantation:role of xanthine/xanthine oxidase.Hepatology2002;36:562-572[PMID:12198648DOI:10.1053/jhep.2002.34616]
29 Kim KM,Kim SS,Yun S,Lee MS,Han DJ,Yang WS,Park JS,Park SK.Uric acid contributes to glomerular filtration rate deterioration in renal transplantation.Nephron Clin Pract 2011;118:c136-c142[PMID:21150221 DOI:10.1159/000320616]
30 Choi HK,Ford ES.Prevalence of the metabolic syndrome in individuals with hyperuricemia.Am J Med 2007;120:442-447[PMID:17466656 DOI:10.1016/j.amjmed.2006.06.040]
31 Li Q,Lu J,Cao X,Shi TT,Feng JP,Yang JK.An Increase in Normal SUA Level Within the Normal Range Predicts Risk of Metabolic Syndrome,Especially in Women:A Cross-Sectional Study.Horm Metab Res 2017;49:338-342[PMID:28351090DOI:10.1055/s-0042-117010]
32 Liu Z,Que S,Zhou L,Zheng S.Dose-response Relationship of Serum Uric Acid with Metabolic Syndrome and Non-alcoholic Fatty Liver Disease Incidence:A Meta-analysis of Prospective Studies.Sci Rep 2015;5:14325[PMID:26395162 DOI:10.1038/srep14325]