Skip to main content
Top
Published in: Hepatology International 4/2016

01-07-2016 | Original Article

Role of cytokine gene polymorphisms in acute and chronic kidney disease following liver transplantation

Authors: Hideya Kamei, Yasuharu Onishi, Taro Nakamura, Masatoshi Ishigami, Nobuyuki Hamajima

Published in: Hepatology International | Issue 4/2016

Login to get access

Abstract

Purpose

Development of renal dysfunction, including acute kidney injury (AKI) and chronic kidney disease (CKD), after liver transplantation (LT) remains a critical issue adversely affecting patient survival in both the short and long term. Previous reports have suggested that inflammatory and antiinflammatory cytokines and their functionally relevant gene polymorphisms may play critical roles in the development of AKI and CKD. However, the involvement of these cytokines and their gene polymorphisms in renal deterioration following LT remains unclear.

Methods

We examined 62 recipients who underwent LT at Nagoya University between 2004 and 2009 and who had survived for at least 1 year. The following gene polymorphisms in recipients were analyzed: tumor necrosis factor-A (TNFA) T-1031C, interleukin-2 (IL2) T-330G, IL10 C-819T, IL13 C-1111T, transforming growth factor-B (TGFB) T29C, and IL4 T-33C.

Results

Thirteen patients (21 %) developed AKI within 4 weeks after LT. Of the investigated gene polymorphisms, the IL4 -33 T/T genotype was significantly associated with higher incidence of AKI compared with the other two genotypes [hazard ratio (HR) = 5.48, 95 % confidence interval (CI) 1.18–25.52, p = 0.03]. On the other hand, 16 patients (26 %) had developed CKD at median follow-up of 9.2 years after LT. We showed the lack of association between investigated gene polymorphisms in recipients and CKD development.

Conclusions

The IL4 -33 T/T genotype might be a risk factor for AKI in LT, and this might contribute to earlier withdrawal of immunosuppressive agents to minimize renal toxicity. In contrast, none of the investigated cytokine gene polymorphisms were associated with CKD.
Literature
1.
go back to reference Busuttil RW, Farmer DG, Yersiz H, et al. Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience. Ann Surg 2005;241:905–916; discussion 16–8 Busuttil RW, Farmer DG, Yersiz H, et al. Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience. Ann Surg 2005;241:905–916; discussion 16–8
2.
go back to reference Barri YM, Sanchez EQ, Jennings LW, et al. Acute kidney injury following liver transplantation: definition and outcome. Liver Transpl 2009;15:475–483 Barri YM, Sanchez EQ, Jennings LW, et al. Acute kidney injury following liver transplantation: definition and outcome. Liver Transpl 2009;15:475–483
3.
go back to reference Bilbao I, Charco R, Balsells J, et al. Risk factors for acute renal failure requiring dialysis after liver transplantation. Clin Transplant 1998;12:123–129 Bilbao I, Charco R, Balsells J, et al. Risk factors for acute renal failure requiring dialysis after liver transplantation. Clin Transplant 1998;12:123–129
4.
go back to reference O’Riordan A, Wong V, McQuillan R, McCormick PA, Hegarty JE, Watson AJ. Acute renal disease, as defined by the RIFLE criteria, post-liver transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg 2007;7:168–176 O’Riordan A, Wong V, McQuillan R, McCormick PA, Hegarty JE, Watson AJ. Acute renal disease, as defined by the RIFLE criteria, post-liver transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg 2007;7:168–176
5.
go back to reference Paramesh AS, Roayaie S, Doan Y, et al. Post-liver transplant acute renal failure: factors predicting development of end-stage renal disease. Clin Transplant 2004;18:94–99 Paramesh AS, Roayaie S, Doan Y, et al. Post-liver transplant acute renal failure: factors predicting development of end-stage renal disease. Clin Transplant 2004;18:94–99
6.
go back to reference Barreto AG, Daher EF, Silva Junior GB, et al. Risk factors for acute kidney injury and 30-day mortality after liver transplantation. Ann Hepatol 2015;14:688–694 Barreto AG, Daher EF, Silva Junior GB, et al. Risk factors for acute kidney injury and 30-day mortality after liver transplantation. Ann Hepatol 2015;14:688–694
7.
go back to reference Cywinski JB, Mascha EJ, You J, et al. Pre-transplant MELD and sodium MELD scores are poor predictors of graft failure and mortality after liver transplantation. Hepatol Int 2011;5:841–849 Cywinski JB, Mascha EJ, You J, et al. Pre-transplant MELD and sodium MELD scores are poor predictors of graft failure and mortality after liver transplantation. Hepatol Int 2011;5:841–849
8.
go back to reference Zhu M, Li Y, Xia Q, et al. Strong impact of acute kidney injury on survival after liver transplantation. Transplant Proc 2010;42:3634–3638 Zhu M, Li Y, Xia Q, et al. Strong impact of acute kidney injury on survival after liver transplantation. Transplant Proc 2010;42:3634–3638
9.
go back to reference Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003;349:931–940 Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003;349:931–940
10.
go back to reference Belopolskaya OB, Smelaya TV, Moroz VV, Golubev AM, Salnikova LE. Clinical associations of host genetic variations in the genes of cytokines in critically ill patients. Clin Exp Immunol 2015;180:531–541 Belopolskaya OB, Smelaya TV, Moroz VV, Golubev AM, Salnikova LE. Clinical associations of host genetic variations in the genes of cytokines in critically ill patients. Clin Exp Immunol 2015;180:531–541
11.
go back to reference McBride WT, Prasad PS, Armstrong M, et al. Cytokine phenotype, genotype, and renal outcomes at cardiac surgery. Cytokine 2013;61:275–284 McBride WT, Prasad PS, Armstrong M, et al. Cytokine phenotype, genotype, and renal outcomes at cardiac surgery. Cytokine 2013;61:275–284
12.
go back to reference Susantitaphong P, Perianayagam MC, Tighiouart H, Liangos O, Bonventre JV, Jaber BL. Tumor necrosis factor alpha promoter polymorphism and severity of acute kidney injury. Nephron Clin Pract 2013;123:67–73 Susantitaphong P, Perianayagam MC, Tighiouart H, Liangos O, Bonventre JV, Jaber BL. Tumor necrosis factor alpha promoter polymorphism and severity of acute kidney injury. Nephron Clin Pract 2013;123:67–73
13.
go back to reference Carrero JJ, Park SH, Axelsson J, Lindholm B, Stenvinkel P. Cytokines, atherogenesis, and hypercatabolism in chronic kidney disease: a dreadful triad. Semin Dial 2009;22:381–386 Carrero JJ, Park SH, Axelsson J, Lindholm B, Stenvinkel P. Cytokines, atherogenesis, and hypercatabolism in chronic kidney disease: a dreadful triad. Semin Dial 2009;22:381–386
14.
go back to reference Okada R, Wakai K, Naito M, et al. Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study. BMC Nephrol 2012;13:2 Okada R, Wakai K, Naito M, et al. Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study. BMC Nephrol 2012;13:2
15.
go back to reference Silverstein DM. Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease. Pediatr Nephrol 2009;24:1445–1452 Silverstein DM. Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease. Pediatr Nephrol 2009;24:1445–1452
16.
go back to reference Kamei H, Masuda S, Nakamura T, et al. Cytokine gene polymorphisms in acute cellular rejection following living donor liver transplantation: analysis of 155 donor–recipient pairs. Hepatol Int 2013;7:916–922 Kamei H, Masuda S, Nakamura T, et al. Cytokine gene polymorphisms in acute cellular rejection following living donor liver transplantation: analysis of 155 donor–recipient pairs. Hepatol Int 2013;7:916–922
17.
go back to reference Williams JR. The Declaration of Helsinki and public health. Bull World Health Organ 2008;86:650–652 Williams JR. The Declaration of Helsinki and public health. Bull World Health Organ 2008;86:650–652
18.
go back to reference Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8:R204–R212 Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8:R204–R212
19.
go back to reference Stevens PE, Levin A. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 2013;158:825–830 Stevens PE, Levin A. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 2013;158:825–830
20.
go back to reference Abdiev S, Ahn KS, Khadjibaev A, et al. Helicobacter pylori infection and cytokine gene polymorphisms in Uzbeks. Nagoya J Med Sci 2010;72:167–172 Abdiev S, Ahn KS, Khadjibaev A, et al. Helicobacter pylori infection and cytokine gene polymorphisms in Uzbeks. Nagoya J Med Sci 2010;72:167–172
21.
go back to reference Hamajima N, Saito T, Matsuo K, Kozaki K, Takahashi T, Tajima K. Polymerase chain reaction with confronting two-pair primers for polymorphism genotyping. Jpn J Cancer Res 2000;91:865–868 Hamajima N, Saito T, Matsuo K, Kozaki K, Takahashi T, Tajima K. Polymerase chain reaction with confronting two-pair primers for polymorphism genotyping. Jpn J Cancer Res 2000;91:865–868
22.
go back to reference Togawa S, Joh T, Itoh M, et al. Interleukin-2 gene polymorphisms associated with increased risk of gastric atrophy from Helicobacter pylori infection. Helicobacter 2005;10:172–178 Togawa S, Joh T, Itoh M, et al. Interleukin-2 gene polymorphisms associated with increased risk of gastric atrophy from Helicobacter pylori infection. Helicobacter 2005;10:172–178
23.
go back to reference Chang CF, Lu TM, Yang WC, Lin SJ, Lin CC, Chung MY. Gene polymorphisms of interleukin-10 and tumor necrosis factor-alpha are associated with contrast-induced nephropathy. Am J Nephrol 2013;37:110–117 Chang CF, Lu TM, Yang WC, Lin SJ, Lin CC, Chung MY. Gene polymorphisms of interleukin-10 and tumor necrosis factor-alpha are associated with contrast-induced nephropathy. Am J Nephrol 2013;37:110–117
24.
go back to reference Jaber BL, Rao M, Guo D, et al. Cytokine gene promoter polymorphisms and mortality in acute renal failure. Cytokine 2004;25:212–219 Jaber BL, Rao M, Guo D, et al. Cytokine gene promoter polymorphisms and mortality in acute renal failure. Cytokine 2004;25:212–219
25.
go back to reference Cuenca AB, Citores MJ, de la Fuente S, et al. TT genotype of transforming growth factor beta1 +869C/T is associated with the development of chronic kidney disease after liver transplantation. Transplant Proc 2014;46:3108–3110 Cuenca AB, Citores MJ, de la Fuente S, et al. TT genotype of transforming growth factor beta1 +869C/T is associated with the development of chronic kidney disease after liver transplantation. Transplant Proc 2014;46:3108–3110
26.
go back to reference Bijlsma FJ, van Kuik J, van Hoffen E, et al. Acute cardiac transplant rejection is associated with low frequencies of interleukin-4 producing helper T-lymphocytes rather than with interleukin-4 promoter or splice variants. Hum Immunol 2002;63:317–323 Bijlsma FJ, van Kuik J, van Hoffen E, et al. Acute cardiac transplant rejection is associated with low frequencies of interleukin-4 producing helper T-lymphocytes rather than with interleukin-4 promoter or splice variants. Hum Immunol 2002;63:317–323
27.
go back to reference Bijlsma FJ, vanKuik J, Tilanus MG, et al. Donor interleukin-4 promoter gene polymorphism influences allograft rejection after heart transplantation. J Heart Lung Transplant 2002;21:340–346 Bijlsma FJ, vanKuik J, Tilanus MG, et al. Donor interleukin-4 promoter gene polymorphism influences allograft rejection after heart transplantation. J Heart Lung Transplant 2002;21:340–346
28.
go back to reference Essner R, Rhoades K, McBride WH, Morton DL, Economou JS. IL-4 down-regulates IL-1 and TNF gene expression in human monocytes. J Immunol 1989;142:3857–3861 Essner R, Rhoades K, McBride WH, Morton DL, Economou JS. IL-4 down-regulates IL-1 and TNF gene expression in human monocytes. J Immunol 1989;142:3857–3861
29.
go back to reference Bozzi A, Reis BS, Pereira PP, Pedroso EP, Goes AM. Interferon-gamma and interleukin-4 single nucleotide gene polymorphisms in paracoccidioidomycosis. Cytokine 2009;48:212–217 Bozzi A, Reis BS, Pereira PP, Pedroso EP, Goes AM. Interferon-gamma and interleukin-4 single nucleotide gene polymorphisms in paracoccidioidomycosis. Cytokine 2009;48:212–217
30.
go back to reference Tindall EA, Severi G, Hoang HN, et al. Comprehensive analysis of the cytokine-rich chromosome 5q31.1 region suggests a role for IL-4 gene variants in prostate cancer risk. Carcinogenesis 2010;31:1748–1754 Tindall EA, Severi G, Hoang HN, et al. Comprehensive analysis of the cytokine-rich chromosome 5q31.1 region suggests a role for IL-4 gene variants in prostate cancer risk. Carcinogenesis 2010;31:1748–1754
31.
go back to reference Mittal RD, Manchanda PK. Association of interleukin (IL)-4 intron-3 and IL-6 -174 G/C gene polymorphism with susceptibility to end-stage renal disease. Immunogenetics 2007;59:159–165 Mittal RD, Manchanda PK. Association of interleukin (IL)-4 intron-3 and IL-6 -174 G/C gene polymorphism with susceptibility to end-stage renal disease. Immunogenetics 2007;59:159–165
32.
go back to reference Yao Q, Lindholm B, Stenvinkel P. Inflammation as a cause of malnutrition, atherosclerotic cardiovascular disease, and poor outcome in hemodialysis patients. Hemodial Int 2004;8:118–129 Yao Q, Lindholm B, Stenvinkel P. Inflammation as a cause of malnutrition, atherosclerotic cardiovascular disease, and poor outcome in hemodialysis patients. Hemodial Int 2004;8:118–129
33.
go back to reference Hiromura K, Kurosawa M, Yano S, Naruse T. Tubulointerstitial mast cell infiltration in glomerulonephritis. Am J Kidney Dis 1998;32:593–599 Hiromura K, Kurosawa M, Yano S, Naruse T. Tubulointerstitial mast cell infiltration in glomerulonephritis. Am J Kidney Dis 1998;32:593–599
34.
go back to reference Tsuda K, Yamanaka K, Kitagawa H, et al. Calcineurin inhibitors suppress cytokine production from memory T cells and differentiation of naive T cells into cytokine-producing mature T cells. PLoS ONE 2012;7:e31465 Tsuda K, Yamanaka K, Kitagawa H, et al. Calcineurin inhibitors suppress cytokine production from memory T cells and differentiation of naive T cells into cytokine-producing mature T cells. PLoS ONE 2012;7:e31465
35.
go back to reference Kim JY, Akalin E, Dikman S, et al. The variable pathology of kidney disease after liver transplantation. Transplantation 2010;89:215–221 Kim JY, Akalin E, Dikman S, et al. The variable pathology of kidney disease after liver transplantation. Transplantation 2010;89:215–221
36.
go back to reference Fussner LA, Charlton MR, Heimbach JK, et al. The impact of gender and NASH on chronic kidney disease before and after liver transplantation. Liver Int 2014;34:1259–1266 Fussner LA, Charlton MR, Heimbach JK, et al. The impact of gender and NASH on chronic kidney disease before and after liver transplantation. Liver Int 2014;34:1259–1266
37.
go back to reference O’Riordan A, Dutt N, Cairns H, et al. Renal biopsy in liver transplant recipients. Nephrol Dial Transplant 2009;24:2276–2282 O’Riordan A, Dutt N, Cairns H, et al. Renal biopsy in liver transplant recipients. Nephrol Dial Transplant 2009;24:2276–2282
38.
go back to reference Weber ML, Ibrahim HN, Lake JR. Renal dysfunction in liver transplant recipients: evaluation of the critical issues. Liver Transpl 2012;18:1290–1301 Weber ML, Ibrahim HN, Lake JR. Renal dysfunction in liver transplant recipients: evaluation of the critical issues. Liver Transpl 2012;18:1290–1301
Metadata
Title
Role of cytokine gene polymorphisms in acute and chronic kidney disease following liver transplantation
Authors
Hideya Kamei
Yasuharu Onishi
Taro Nakamura
Masatoshi Ishigami
Nobuyuki Hamajima
Publication date
01-07-2016
Publisher
Springer India
Published in
Hepatology International / Issue 4/2016
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-016-9721-x

Other articles of this Issue 4/2016

Hepatology International 4/2016 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.