IL-6 Is Associated with Progression of Coronary Artery Calcification and Mortality in Incident Dialysis Patients

Overview

Journal Am J Nephrol

Publisher Karger

Specialty Nephrology

Date 2021 Sep 18

PMID 34535589

Citations 12

Authors

Neil Roy

Sylvia E Rosas

Affiliations

Soon will be listed here.

Abstract

Introduction: Inflammation is important in the pathogenesis of atherosclerosis. Elevated interleukin-6 (IL-6) is associated with cardiovascular events and also predicts mortality in individuals with CKD. Our goal was to determine the association between IL-6, FGF23, and high-sensitivity C-reactive protein (hsCRP) on coronary artery calcification (CAC) progression and mortality in incident dialysis patients without prior coronary events.

Methods: A prospective cohort of incident adult dialysis participants had CAC measured by ECG-triggered multislice CT scans at baseline and at least 12 months later. Lipids, mineral metabolism markers, FGF23, and inflammatory markers, such as IL-6 and hsCRP, were measured at the baseline visit.

Results: Participants in the high IL-6 tertile had the highest baseline CAC score (133.25 [10.35-466.15]) compared to the low (0.25 [0-212.2]) and intermediate (29.55 [0-182.85]) tertiles. Almost half of the participants with high IL-6 (15 of 32 [46.9%]) experienced progression of CAC compared to participants with low (8 of 32 [25%]) and intermediate (9 of 32 [28.1%]) (p = 0.05) IL-6 levels. Each log increase in IL-6 was associated with increase in death (hazard ratio 2.2, 95% CI: 1.2-3.8; p = 0.01). After adjusting for smoking, age, gender, race, diabetes, phosphate, and baseline calcium score, IL-6 (log) was associated with 2.2 times (95% CI: 1.1-4.6; p = 0.03) increase in death.

Conclusion: IL-6 is associated with progression of CAC and mortality in incident dialysis patients.

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References

Scialla J, Xie H, Rahman M, Anderson A, Isakova T, Ojo A . Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol. 2013; 25(2):349-60. PMC: 3904568. DOI: 10.1681/ASN.2013050465. View

Pecoits-Filho R, Barany P, Lindholm B, Heimburger O, Stenvinkel P . Interleukin-6 is an independent predictor of mortality in patients starting dialysis treatment. Nephrol Dial Transplant. 2002; 17(9):1684-8. DOI: 10.1093/ndt/17.9.1684. View

Gibas M, Miszczak-Smialek J, Madry E, Gluszek J, Witmanowski H, Piotrowski J . Influence of preventive therapy with quinapril on IL-6 level in patients with chronic stable angina. Pharmacol Rep. 2007; 59(3):330-8. View

Ozkok A, Kekik C, Karahan G, Sakaci T, Ozel A, Unsal A . FGF-23 associated with the progression of coronary artery calcification in hemodialysis patients. BMC Nephrol. 2013; 14:241. PMC: 3830511. DOI: 10.1186/1471-2369-14-241. View

Shantouf R, Budoff M, Ahmadi N, Ghaffari A, Flores F, Gopal A . Total and individual coronary artery calcium scores as independent predictors of mortality in hemodialysis patients. Am J Nephrol. 2010; 31(5):419-25. PMC: 2883846. DOI: 10.1159/000294405. View

Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C . Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int. 1999; 55(2):648-58. DOI: 10.1046/j.1523-1755.1999.00273.x. View

Kaminska J, Stopinski M, Mucha K, Jedrzejczak A, Golebiowski M, Niewczas M . IL 6 but not TNF is linked to coronary artery calcification in patients with chronic kidney disease. Cytokine. 2019; 120:9-14. DOI: 10.1016/j.cyto.2019.04.002. View

Zoccali C, Tripepi G, Mallamaci F . Dissecting inflammation in ESRD: do cytokines and C-reactive protein have a complementary prognostic value for mortality in dialysis patients?. J Am Soc Nephrol. 2006; 17(12 Suppl 3):S169-73. DOI: 10.1681/ASN.2006080910. View

Jung H, Kim S, Han H . Inflammation, mineral metabolism and progressive coronary artery calcification in patients on haemodialysis. Nephrol Dial Transplant. 2006; 21(7):1915-20. DOI: 10.1093/ndt/gfl118. View

10.

Sun J, Axelsson J, Machowska A, Heimburger O, Barany P, Lindholm B . Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD. Clin J Am Soc Nephrol. 2016; 11(7):1163-1172. PMC: 4934843. DOI: 10.2215/CJN.10441015. View

11.

Willerson J, Ridker P . Inflammation as a cardiovascular risk factor. Circulation. 2004; 109(21 Suppl 1):II2-10. DOI: 10.1161/01.CIR.0000129535.04194.38. View

12.

Brancaccio D, Tetta C, Gallieni M, Panichi V . Inflammation, CRP, calcium overload and a high calcium-phosphate product: a "liaison dangereuse". Nephrol Dial Transplant. 2002; 17(2):201-3. DOI: 10.1093/ndt/17.2.201. View

13.

Humphries S, Luong L, Ogg M, Hawe E, Miller G . The interleukin-6 -174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur Heart J. 2001; 22(24):2243-52. DOI: 10.1053/euhj.2001.2678. View

14.

Jean G, Terrat J, Vanel T, Hurot J, Lorriaux C, Mayor B . High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients. Nephrol Dial Transplant. 2009; 24(9):2792-6. DOI: 10.1093/ndt/gfp191. View

15.

Qureshi A, Alvestrand A, Divino-Filho J, Gutierrez A, Heimburger O, Lindholm B . Inflammation, malnutrition, and cardiac disease as predictors of mortality in hemodialysis patients. J Am Soc Nephrol. 2002; 13 Suppl 1:S28-36. View

16.

Rao M, Guo D, Perianayagam M, Tighiouart H, Jaber B, Pereira B . Plasma interleukin-6 predicts cardiovascular mortality in hemodialysis patients. Am J Kidney Dis. 2005; 45(2):324-33. DOI: 10.1053/j.ajkd.2004.09.018. View

17.

Honda H, Qureshi A, Heimburger O, Barany P, Wang K, Pecoits-Filho R . 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. 2005; 47(1):139-48. DOI: 10.1053/j.ajkd.2005.09.014. View

18.

Danesh J, Wheeler J, Hirschfield G, Eda S, Eiriksdottir G, Rumley A . C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004; 350(14):1387-97. DOI: 10.1056/NEJMoa032804. View

19.

Barreto D, Barreto F, Carvalho A, Cuppari L, Cendoroglo M, Draibe S . Coronary calcification in hemodialysis patients: the contribution of traditional and uremia-related risk factors. Kidney Int. 2005; 67(4):1576-82. DOI: 10.1111/j.1523-1755.2005.00239.x. View

20.

Gutierrez O, Mannstadt M, Isakova T, Rauh-Hain J, Tamez H, Shah A . Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008; 359(6):584-92. PMC: 2890264. DOI: 10.1056/NEJMoa0706130. View