Nontraditional Biomarkers for Cardiovascular Disease in Patients With Chronic Kidney Disease

Main Article Content

Ittikorn Spanuchart
Arkom Nongnuch
Youg Liu

Abstract

Cardiovascular disease (CVD) is the leading cause of death among patients who have chronic kidney disease (CKD). Nowadays, CKD per se is considered one of the coronary heart disease (CHD) risk equivalents. Apart from traditional CVD risk factors, there are several possible determinants for CVD in patients with CKD, for example, uremic toxins, increased inflammatory stage, abnormal bone mineral metabolism, and positive calcium balance. In this narrative review, we offer a summary of the extensively studied biomarkers for CVD in patients with CKD, including uremic toxins (p-cresol, indoxyl sulfate, and advanced glycated end products), and a novel indicator of arterial stiffness, cardio-ankle vascular index (CAVI), which is an independent prognostic predictor for CVD. For the uremic toxins, we reviewed their metabolisms, particularly, how the reduced renal function in CKD patients affect their clearance and their clearance with dialysis. Also, we pay attention to the recent evidence on how those uremic toxins contribute to CVD and their clinical associations. We do not include the possible treatment targeting at those uremic toxins. As for the novel indicator of arterial stiffness, we reviewed the clinical application of CAVI in comparison to the standard indicator for arterial stiffness, pulse wave velocity.


 

Article Details

How to Cite
Spanuchart, I., Nongnuch, A., & Liu, Y. (2020). Nontraditional Biomarkers for Cardiovascular Disease in Patients With Chronic Kidney Disease. Ramathibodi Medical Journal, 43(2), 51 - 60. https://doi.org/10.33165/rmj.2020.43.2.230208
Section
Review Articles

References

1. Liabeuf S, Barreto DV, Barreto FC, et al. Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease. Nephrol Dial Transplant. 2010;25(4):1183-1191. doi:10.1093/ndt/gfp592.

2. Lesaffer G, De Smet R, Lameire N, Dhondt A, Duym P, Vanholder R. Intradialytic removal of protein-bound uraemic toxins: role of solute characteristics and of dialyser membrane. Nephrol Dial Transplant. 2000;15(1):50-57. doi:10.1093/ndt/15.1.50.

3. Meert N, Waterloos MA, Van Landschoot M, et al. Prospective evaluation of the change of predialysis protein-bound uremic solute concentration with postdilution online hemodiafiltration. Artif Organs. 2010;34(7):580-525. doi:10.1111/j.1525-1594.2010.01005.x.

4. Tijink MS, Wester M, Glorieux G, et al. Mixed matrix hollow fiber membranes for removal of protein-bound toxins from human plasma. Biomaterials. 2013;34(32):7819-7828. doi:10.1016/j.biomaterials.2013.07.008.

5. Evenepoel P, Bammens B, Verbeke K, Vanrenterghem Y. Superior dialytic clearance of beta(2)-microglobulin and p-cresol by high-flux hemodialysis as compared to peritoneal dialysis. Kidney Int. 2006;70(4):794-799. doi:10.1038/sj.ki.5001640.

6. Bammens B, Evenepoel P, Keuleers H, Verbeke K, Vanrenterghem Y. Free serum concentrations of the protein-bound retention solute p-cresol predict mortality in hemodialysis patients. Kidney Int. 2006;69(6):1081-1087. doi:10.1038/sj.ki.5000115.

7. Pasternack A, Kuhlbaeck B, Tallgren LG. Serum indican in renal disease. Acta Med Scand. 1964;176:751-756. doi:10.1111/j.0954-6820.1964.tb00683.x.

8. Barreto FC, Barreto DV, Liabeuf S, et al. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol. 2009;4(10):1551-1558. doi:10.2215/CJN.03980609.

9. De Smet R, Dhondt A, Eloot S, Galli F, Waterloos MA, Vanholder R. Effect of the super-flux cellulose triacetate dialyser membrane on the removal of non-protein-bound and protein-bound uraemic solutes. Nephrol Dial Transplant. 2007;22(7):2006-2012. doi:10.1093/ndt/gfm065.

10. Krieter DH, Kerwagen S, Rüth M, Lemke HD, Wanner C. Differences in dialysis efficacy have limited effects on protein-bound uremic toxins plasma levels over time. Toxins (Basel). 2019;11(1). pii: E47. doi:10.3390/toxins11010047.

11. Choi SY, Park HE, Seo H, Kim M, Cho SH, Oh BH. Arterial stiffness using cardio-ankle vascular index reflects cerebral small vessel disease in healthy young and middle aged subjects. J Atheroscler Thromb. 2013;20(2):178-185. doi:10.5551/jat.14753.

12. Niwa T. Indoxyl sulfate is a nephro-vascular toxin. J Ren Nutr. 2010;20(5 Suppl):S2-S6. doi:10.1053/j.jrn.2010.05.002.

13. Sun CY, Chang SC, Wu MS. Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLoS One. 2012;7(3):e34026. doi:10.1371/journal.pone.0034026.

14. Lin CJ, Liu HL, Pan CF, et al. Indoxyl sulfate predicts cardiovascular disease and renal function deterioration in advanced chronic kidney disease. Arch Med Res. 2012;43(6):451-456. doi:10.1016/j.arcmed.2012.08.002.

15. Lin CJ, Wu V, Wu PC, Wu CJ. Meta-analysis of the associations of p-cresyl sulfate (PCS) and indoxyl sulfate (IS) with cardiovascular events and all-cause mortality in patients with chronic renal failure. PLoS One. 2015;10(7):e0132589. doi:10.1371/journal.pone.0132589.

16. Nongnuch A, Davenport A. The effect of vegetarian diet on skin autofluorescence measurements in haemodialysis patients. Br J Nutr. 2015;113(7):1040-1043. doi:10.1017/S0007114515000379.

17. Loughrey CM, Young IS, Lightbody JH, McMaster D, McNamee PT, Trimble ER. Oxidative stress in haemodialysis. QJM. 1994;87(11):679-683.

18. Jadoul M, Ueda Y, Yasuda Y, et al. Influence of hemodialysis membrane type on pentosidine plasma level, a marker of “carbonyl stress”. Kidney Int. 1999;55(6):2487-2492. doi:10.1046/j.1523-1755.1999.00468.x.

19. Rebholz CM, Astor BC, Grams ME, et al. Association of plasma levels of soluble receptor for advanced glycation end products and risk of kidney disease: the atherosclerosis risk in communities study. Nephrol Dial Transplant. 2015;30(1):77-83. doi:10.1093/ndt/gfu282.

20. Graaff R, Arsov S, Ramsauer B, et al. Skin and plasma autofluorescence during hemodialysis: a pilot study. Artif Organs. 2014;38(6):515-518. doi:10.1111/aor.12205.

21. Henle T, Deppisch R, Beck W, Hergesell O, Hänsch GM, Ritz E. Advanced glycated end-products (AGE) during haemodialysis treatment: discrepant results with different methodologies reflecting the heterogeneity of AGE compounds. Nephrol Dial Transplant. 1999;14(8):1968-1975. doi:10.1093/ndt/14.8.1968.

22. Nongnuch A, Davenport A. The effect of on-line hemodiafiltration, vegetarian diet, and urine volume on advanced glycosylation end products measured by changes in skin auto-fluorescence. Artif Organs. 2018;42(11):1078-1085. doi:10.1111/aor.13143.

23. Nongnuch A, Davenport A. Skin autofluorescence advanced glycosylation end products as an independent predictor of mortality in high flux haemodialysis and haemodialysis patients. Nephrology (Carlton). 2015;20(11):862-867. doi:10.1111/nep.12519.

24. Sun CK. Cardio-ankle vascular index (CAVI) as an indicator of arterial stiffness. Integr Blood Press Control. 2013;6:27-38. doi:10.2147/IBPC.S34423.

25. Yambe T, Yoshizawa M, Saijo Y, et al. Brachio-ankle pulse wave velocity and cardio-ankle vascular index (CAVI). Biomed Pharmacother. 2004;58 Suppl 1:S95-S98. doi:10.1016/s0753-3322(04)80015-5.

26. Kim KJ, Lee BW, Kim HM, et al. Associations between cardio-ankle vascular index and microvascular complications in type 2 diabetes mellitus patients. J Atheroscler Thromb. 2011;18(4):328-336. doi:10.5551/jat.5983.

27. Korkmaz L, Adar A, Korkmaz AA, et al. Atherosclerosis burden and coronary artery lesion complexity in acute coronary syndrome patients. Cardiol J. 2012;19(3):295-300. doi:10.5603/cj.2012.0052.

28. Kimura H, Takeda K, Tsuruya K, et al. Left ventricular mass index is an independent determinant of diastolic dysfunction in patients on chronic hemodialysis: a tissue Doppler imaging study. Nephron Clin Pract. 2011;117(1):c67-c73. doi:10.1159/000319649.

29. Mert M, Dursun B, Yağcı AB, Çetin Kardeşler A, Şenol H, Demir S. Cardio-ankle vascular index is linked to deranged metabolic status, especially high HbA1c and monocyte-chemoattractant-1 protein, in predialysis chronic kidney disease. Int Urol Nephrol. 2020;52(1):137-145. doi:10.1007/s11255-019-02336-6.

30. Au-Yeung KK, Yip JC, Siow YL, O K. Folic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophages. Can J Physiol Pharmacol. 2006;84(1):141-147. doi:10.1139/Y05-136.

31. Manolov V, Petrova J, Bogov B, et al. Evaluation of hepcidin and atherosclerosis in dialysis patients. Clin Lab. 2017;63(11):1787-1792. doi:10.7754/Clin.Lab.2017.170336.

32. Nongnuch A, Panorchan K, Davenport A. Brain-kidney crosstalk. Crit Care. 2014;18(3):225. doi:10.1186/cc13907.

33. Kielstein JT, Impraim B, Simmel S, et al. Cardiovascular effects of systemic nitric oxide synthase inhibition with asymmetrical dimethylarginine in humans. Circulation. 2004;109(2):172-177. doi:10.1161/01.CIR.0000105764.22626.B1.

34. Schepers E, Glorieux G, Dhondt A, Leybaert L, Vanholder R. Role of symmetric dimethylarginine in vascular damage by increasing ROS via store-operated calcium influx in monocytes. Nephrol Dial Transplant. 2009;24(5):1429-1435. doi:10.1093/ndt/gfn670.

35. Scholze A, Jankowski V, Henning L, et al. Phenylacetic acid and arterial vascular properties in patients with chronic kidney disease stage 5 on hemodialysis therapy. Nephron Clin Pract. 2007;107(1):c1-c6. doi:10.1159/000105137.

36. Bonito B, Silva AP, Rato F, Santos N, Neves PL. Resistin as a predictor of cardiovascular hospital admissions and renal deterioration in diabetic patients with chronic kidney disease. J Diabetes Complications. 2019;33(11):107422. doi:10.1016/j.jdiacomp.2019.107422.

37. Albarello K, dos Santos GA, Bochi GV, et al. Ischemia modified albumin and carbonyl protein as potential biomarkers of protein oxidation in hemodialysis. Clin Biochem. 2012;45(6):450-454. doi:10.1016/j.clinbiochem.2.012.01.031.

Most read articles by the same author(s)