Top

Published in:

01-10-2014 | Original Article

Neutrophil gelatinase-associated lipocalin levels associated with cardiovascular disease in chronic kidney disease patients

Authors: Fumihiko Furuya, Hiroki Shimura, Hiroshi Yokomichi, Kazuya Takahashi, Daiichiro Akiyama, Chikako Asakawa, Ayako Okamura, Ai Motosugi, Kazutaka Haraguchi, Zentaro Yamagata, Tetsuro Kobayashi

Published in: Clinical and Experimental Nephrology | Issue 5/2014

Abstract

Background

Elevated levels of neutrophil gelatinase-associated lipocalin (NGAL) have been reported in patients with cardiovascular disease (CVD), heart failure, and stroke. We assessed the relationships between serum levels of NGAL and the prevalence of CVD, and clarified the prognostic usefulness of systemic NGAL levels in hemodialysis (HD) patients.

Methods

Eighty-eight HD patients were followed up for 1 year. Logistic regression analyses were used to investigate the relationship between de novo CVD status and NGAL levels as well as other risk factors.

Results

During follow-up, CVD events occurred in 20 patients. Initial serum levels of NGAL and brain natriuretic peptide of HD patients with de novo CVD were significantly higher than those of HD patients without de novo CVD. Multivariate logistic regression analyses showed that initial serum levels of NGAL were independent risk factors for de novo CVD in HD patients. When patients were classified on the basis of NGAL quartiles, multiple logistic regression analyses demonstrated that the highest quartile of NGAL level showed an increased odds ratio for the prevalence of CVD.

Conclusion

These findings suggest that NGAL levels can be used to detect the prevalence of CVD in HD patients with or without diabetes.

Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108(17):2154–69. doi:10.1161/01.CIR.0000095676.90936.80.PubMedCrossRef

Nakamura K, Okamura T, Hayakawa T, Kadowaki T, Kita Y, Ohnishi H, et al. Chronic kidney disease is a risk factor for cardiovascular death in a community-based population in Japan: NIPPON DATA90. Circ J. 2006;70(8):954–9 pii: JST.JSTAGE/circj/70.954.PubMedCrossRef

Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis. 2008;52(3):595–605. doi:10.1053/j.ajkd.2008.01.020.PubMedCrossRef

Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR, et al. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol. 2009;4(2):337–44. doi:10.2215/CJN.03530708.PubMedCrossRefPubMedCentral

Bolignano D, Coppolino G, Lacquaniti A, Buemi M. From kidney to cardiovascular diseases: NGAL as a biomarker beyond the confines of nephrology. Eur J Clin Invest. 2010;40(3):273–6. doi:10.1111/j.1365-2362.2010.02258.x.PubMedCrossRef

Hemdahl AL, Gabrielsen A, Zhu C, Eriksson P, Hedin U, Kastrup J, et al. Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction. Arterioscler Thromb Vasc Biol. 2006;26(1):136–42. doi:10.1161/01.ATV.0000193567.88685.f4.PubMedCrossRef

Yndestad A, Landro L, Ueland T, Dahl CP, Flo TH, Vinge LE, et al. Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin in clinical and experimental heart failure. Eur Heart J. 2009;30(10):1229–36. doi:10.1093/eurheartj/ehp088.PubMedCrossRef

Takenaka T, Hoshi H, Kato N, Kobayashi K, Takane H, Shoda J, et al. Cardio-ankle vascular index to screen cardiovascular diseases in patients with end-stage renal diseases. J Atheroscler Thromb. 2008;15(6):339–44 pii: JST.JSTAGE/jat/E584.PubMedCrossRef

Suzuki M, Hada Y, Akaishi M, Hiroe M, Aonuma K, Tsubakihara Y, et al. Effects of anemia correction by erythropoiesis-stimulating agents on cardiovascular function in non-dialysis patients with chronic kidney disease. Int Heart J. 2012;53(4):238–43 pii: DN/JST.JSTAGE/ihj/53.238.PubMedCrossRef

10.

Hsu HJ, Yen CH, Chen CK, Hsu KH, Hsiao CC, Lee CC, et al. Low plasma DHEA-S increases mortality risk among male hemodialysis patients. Exp Gerontol. 2012;47(12):950–7. doi:10.1016/j.exger.2012.08.012.PubMedCrossRef

11.

Morishita Y, Hanawa S, Chinda J, Iimura O, Tsunematsu S, Kusano E. Effects of aliskiren on blood pressure and the predictive biomarkers for cardiovascular disease in hemodialysis-dependent chronic kidney disease patients with hypertension. Hypertens Res. 2011;34(3):308–13. doi:10.1038/hr.2010.238.PubMedCrossRef

12.

Carrero JJ, Qureshi AR, Parini P, Arver S, Lindholm B, Barany P, et al. Low serum testosterone increases mortality risk among male dialysis patients. J Am Soc Nephrol. 2009;20(3):613–20. doi:10.1681/ASN.2008060664.PubMedCrossRefPubMedCentral

13.

Terawaki H, Nakayama M, Miyazawa E, Murata Y, Nakayama K, Matsushima M et al. Effect of allopurinol on cardiovascular incidence among hypertensive nephropathy patients: the Gonryo study. Clin Exp Nephrol. 2012;17(4):549–53. doi:10.1007/s10157-012-0742-z.

14.

Iimori S, Noda Y, Okado T, Naito S, Toda T, Chida Y, et al. Baseline characteristics and prevalence of cardiovascular disease in newly visiting or referred chronic kidney disease patients to nephrology centers in Japan: a prospective cohort study. BMC Nephrol. 2013;14:152. doi:10.1186/1471-2369-14-152.PubMedCrossRefPubMedCentral

15.

Goto T, Takase H, Toriyama T, Sugiura T, Kurita Y, Tsuru N, et al. Increased circulating levels of natriuretic peptides predict future cardiac event in patients with chronic hemodialysis. Nephron. 2002;92(3):610–5 pii: 64100.PubMedCrossRef

16.

Paulsson J, Dadfar E, Held C, Jacobson SH, Lundahl J. Activation of peripheral and in vivo transmigrated neutrophils in patients with stable coronary artery disease. Atherosclerosis. 2007;192(2):328–34. doi:10.1016/j.atherosclerosis.2006.08.003.PubMedCrossRef

17.

Palazzuoli A, Beltrami M, Pellegrini M, Nuti R. Natriuretic peptides and NGAL in heart failure: does a link exist? Clin Chim Acta. 2012;413(23–24):1832–8. doi:10.1016/j.cca.2012.07.010.PubMedCrossRef

18.

Rao M, Guo D, Jaber BL, Sundaram S, Cendoroglo M, King AJ, et al. Dialyzer membrane type and reuse practice influence polymorphonuclear leukocyte function in hemodialysis patients. Kidney Int. 2004;65(2):682–91. doi:10.1111/j.1523-1755.2004.00429.x.PubMedCrossRef

19.

Sommer G, Weise S, Kralisch S, Lossner U, Bluher M, Stumvoll M, et al. Lipocalin-2 is induced by interleukin-1beta in murine adipocytes in vitro. J Cell Biochem. 2009;106(1):103–8. doi:10.1002/jcb.21980.PubMedCrossRef

20.

Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003;14(10):2534–43.PubMedCrossRef

21.

Nickolas TL, O’Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med. 2008;148(11):810–9 pii: 148/11/810.PubMedCrossRefPubMedCentral

22.

Paragas N, Qiu A, Zhang Q, Samstein B, Deng SX, Schmidt-Ott KM, et al. The Ngal reporter mouse detects the response of the kidney to injury in real time. Nat Med. 2011;17(2):216–22. doi:10.1038/nm.2290.PubMedCrossRefPubMedCentral

23.

Shirai K, Utino J, Otsuka K, Takata M. A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI). J Atheroscler Thromb. 2006;13(2):101–7 pii: JST.JSTAGE/jat/13.101.PubMedCrossRef

Title: Neutrophil gelatinase-associated lipocalin levels associated with cardiovascular disease in chronic kidney disease patients
Authors: Fumihiko Furuya
Hiroki Shimura
Hiroshi Yokomichi
Kazuya Takahashi
Daiichiro Akiyama
Chikako Asakawa
Ayako Okamura
Ai Motosugi
Kazutaka Haraguchi
Zentaro Yamagata
Tetsuro Kobayashi
Publication date: 01-10-2014
Publisher: Springer Japan
Published in: Clinical and Experimental Nephrology / Issue 5/2014
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI: https://doi.org/10.1007/s10157-013-0923-4

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2014

Thromboembolic complications in childhood nephrotic syndrome: a clinical profile

A microarray analysis of urinary microRNAs in renal diseases

Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephropathy

Blood lead and cadmium levels and renal function in Korean adults

Significance of combined cyclosporine−prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial

Erratum to: Blood lead and cadmium levels and renal function in Korean adults

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials