×
Home Current Archive Editorial board
News Contact
Review paper

Fetuin-A Thr256Ser gene polymorphism as a mortality predictor in patients with chronic kidney disease on maintenance haemodialysis in Medan, Indonesia

By
Riri Andri Muzasti Orcid logo ,
Riri Andri Muzasti
Contact Riri Andri Muzasti

Division of Nephrology and Hypertension, Department of Internal Medicine, Universitas Sumatera Utara, Medan, Indonesia

Dr Suhardjono ,
Dr Suhardjono

Division of Nephrology and Hypertension, Department of Internal Medicine, University Indonesia, Jakarta, Indonesia

Bambang Purwanto ,
Bambang Purwanto

Division of Nephrology and Hypertension, Department of Internal Medicine, University Negeri Surakarta,

Rosita Juwita Sembiring
Rosita Juwita Sembiring

Department of Clinical Pathology, Universitas Sumatera Utara, Medan, Indonesia

Abstract

Aim
To investigate an impact of Fetuin-A Thr256Ser gene polymorphism on the mortality rate of chronic kidney disease on maintenance haemodialysis patients in Indonesia.
Methods
This is an analytic-longitudinal observational study using survival analysis with nine-month follow up on 106 maintenance haemodialysis patients. The PCR-RFLP is used to determine Fetuin-A Thr256Ser gene polymorphism and Fetuin-A serum level measured by using ELISA methods. We use time-independent cox regression analysis to investigate factors that contribute to patient survival.
Results
The mean survival time of this study is 8.49±1.53 months, with a median survival of 9 months (range 1-9 months). Among 12 (11.3%) deceased patients, most of them carried GG genotype with 8.87 times risk of mortality compared to those with CC+CG genotype (p=0.005). The group of patients with IL-6 level ≥86.9 pg/mL had higher mortality with 3.64 times greater risk compared to those with IL-6 level, <86.9 pg/mL (p=0.03).
Conclusion
This study revealed a significant dominance independent impact of the Fetuin-A Thr256Ser gene polymorphism on the survival rate of maintenance haemodialysis patients. These results suggest that genotype variation of Fetuin-A gene could be a potential marker to identify high mortality risk in Indonesia's maintenance haemodialysis patients, especially in Medan.

References

1.
Bláha V, Mistrík E, Dusilová-Sulková S, Kalousová M, Andrýs C, Bláha M, et al. Circulating fetuin-A predicts early mortality in chronic haemodialysis patients. Clin Biochem. 2009. p. 996–1000.
2.
Osawa M, Yuasa I, Kitano T, Henke J. Haplotype analysis of the human α2-HS glycoprotein (fetuin) gene. Ann Hum Genet. 2001. p. 27–34.
3.
Jensen M, Jensen R, Mukamal K, Guo X, Yao J, Sun Q, et al. Detection of genetic loci associated with plasma fetuin-A: a meta-analysis of genome-wide association studies from the CHAR-GE Consortium. Hum Mol Genet. 2017. p. 2156–63.
4.
Schinke T, Amendt C, Trindl A, Pöschke O, Müller-Esterl W, Wjjobc JD. The serum protein α2-HS glycoprotein/fetuin inhibits apatite formation in vitro and mineralizing calvaria cells, a possible role in mineralization and calcium homeostasis. J Biol Chem. 1996. p. 20789–96.
5.
Ix J, Shlipak M, Brandenburg V, Ali S, Ketteler M, Whooley M. Association between human fetuin-A and the metabolic syndrome data from the heart and soul study. Circulation. 2006. p. 1760–7.
6.
Rjki M. An emerging role for fetuin-A as a contributor to morbidity and mortality in chronic kidney disease. Kidney Int. 2007. p. 137–40.
7.
Stenvinkel P, Wang K, Qureshi A, Axelsson J, Pecoits-Filho R, Gao P, et al. Low fetuin-A levels are associated with cardiovascular death: impact of variations in the gene encoding fetuin. Kidney Int. 2005. p. 2383–92.
8.
Verduijn M, Prein R, Stenvinkel P, Carrero J, Le Cessie S, Witasp A, et al. Is fetuin-A a mortality risk factor in dialysis patients or a mere risk marker? A Mendelian randomization approach. Nephrol Dial Transplant. 2011. p. 239–45.
9.
US Renal Data System. USRDS 2010 Annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. 2010.
10.
Sibarani H, Muzasti R, Lubis H. Proceedings of IOP Conference Series: Earth and Environmental Science.
11.
Robinson B, Zhang J, Morgenstern H, Bradbury B, Ng L, Mccullough K, et al. World-wide, mortality is a high risk soon after initiation of haemodialysis. Kidney Int. 2014. p. 158–65.
12.
Renal I, Registry. Report on Indonesian Renal Registry. 2017.
13.
Prodjosudjadi W, Suhardjono A, Disease. End-stage renal disease in Indonesia: treatment development. Ethn Dis. 2009. p. 1–33.
14.
Pippias M, Jager K, Kramer A, Leivestad T, Sánchez M, Caskey F, et al. The changing trends and outcomes in renal replacement therapy: data from the ERA-EDTA Registry. Nephrol Dial Transplant. 2016. p. 831–41.
15.
USRDS 2015 Annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. US Renal Data System; 2015.
16.
Georgianos P, Agarwal R. Hypertension in chronic kidney disease: Nephrology Dialysis Transplantation notable 2017 advances. Nephrol Dial Transplant. 2019. p. 1–4.
17.
Maharem D, Gomaa S, Ghandor E, M, Matrawy M, Zaytoun K, et al. Association of serum fetuin-A and fetuin-A gene polymorphism in relation to mineral and bone disorders in patients with chronic kidney disease. The EJMHG. 2013. p. 337–52.
18.
Weng C, Hu C, Yen T, Hsu C, Huang W. Nutritional predictors of mortality in long term haemodialysis patients. Sci Rep. 2016. p. 35639.
19.
Amaral S, Hwang W, Fivush B, Neu A, Frankenfield D, Furth S. Serum albumin level and risk for mortality and hospitalization in adolescents on haemodialysis. Clin J Am Soc Nephrol. 2008. p. 759–67.
20.
De Mutsert R, Grootendorst D, Indemans F, Boeschoten E, Krediet R, Dekker F. Netherlands Cooperative Study on the Adequacy of Dialysis-II Study Group. Association between serum albumin and mortality in dialysis patients is partly explained by inflammation, and not by malnutrition. J Ren Nutr. 2009. p. 127–35.
21.
Chung S, Chu W, Lee H, Kim Y, Lee I, Lindholm B, et al. Peritoneal transport characteristics, comorbid diseases, and survival in CAPD patients. Perit Dial Int. 2000. p. 541–7.
22.
Lau W, Kalantar-Zadeh K, Vaziri N. The gut as a source of inflammation in chronic kidney disease. Nephron. 2015. p. 92–8.
23.
Beberashvili I, Sinuani I, Azar A, Yasur H, Shapiro G, Feldman L, et al. IL-6 levels, nutritional status, and mortality in prevalent haemodialysis patients. Clin J Am Soc Nephrol. 2011. p. 2253–63.
24.
Honda H, Qureshi A, Heimbürger O, Barany P, Wang K, Pecoits-Filho R, et al. Serum albumin, C-reactive protein, interleukin 6, and fetuin-A as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis. 2006. p. 139–48.
25.
Metry G, Stenvinkel P, Qureshi A, Carrero J, Yilmaz M, Bárány P, et al. Low serum fetuin-A concentration predicts poor outcomes only in the presence of inflammation in prevalent haemodialysis patients. Eur J Clin Invest. 2008. p. 804–11.
26.
Maréchal C, Schlieper G, Nguyen P, Krüger T, Coche E, Robert A, et al. Serum fetuin-A levels are associated with vascular calcifications and predict cardiovascular events in renal transplant recipients. Clin J Am Soc Nephrol. 2011. p. 974–85.
27.
Hermans M, Brandenburg V, Ketteler M, Kooman J, Van Der Sande F, Boeschoten E, et al. Association of serum fetuin-A levels with mortality in dialysis patients. Kidney Int. 2007. p. 202–7.
28.
Ketteler M, Bongartz P, Westenfeld R, Wildberger J, Mahnken A, Böhm R, et al. Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a crosssectional study. Lancet. 2003. p. 827–33.
29.
Blacher J, Guerin A, Pannier B, Marchais S. London GMJH. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension. 2001. p. 938–42.

Citation

Authors retain copyright. This work is licensed under a Creative Commons Attribution 4.0 International License. Creative Commons License

 

Article metrics

Google scholar: See link

The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.