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The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin with Progression from CKD to ESRD.
Clin J Am Soc Nephrol. 2016 12 07; 11(12):2141-2149.CJ

Abstract

BACKGROUND AND OBJECTIVES

Elevated levels of urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are associated with negative outcomes in CKD. Our study aimed to explore the prognostic accuracy of blood levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin for progression to ESRD, major adverse cardiovascular events, and death in a large cohort of adult patients with all-cause nondialysis-dependent CKD stages 3-5. We considered whether these factors improve prediction in relation to traditional biomarkers and clinical parameters.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS

Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were measured on baseline plasma samples from 1982 patients who were recruited to the Chronic Renal Insufficiency Standards Implementation Study between the start of June of 2002 and the start of June of 2013. Associations with study end points were assessed using Cox regression models, receiver operator characteristic curve analyses, and reclassification statistics.

RESULTS

Over a median follow-up of 29.5 months (interquartile range, 14.9-53.5), 21.6% of patients progressed to ESRD, 27% died, and 6.6% suffered a major adverse cardiovascular event. Higher blood levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were independently associated with a greater risk for ESRD (hazard ratio, 1.25; 95% confidence interval, 1.10 to 1.43; P<0.001 and hazard ratio, 1.35; 95% confidence interval, 1.14 to 1.59; P≤0.001, respectively, per 1 SD higher biomarker concentration). There was no association with risk for cardiovascular events or death. The addition of biomarkers to our baseline risk model of traditional clinical characteristics and laboratory parameters did not significantly improve model discrimination or risk reclassification.

CONCLUSIONS

In patients with moderate to severe CKD, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin blood levels are independent risk factors for progression to ESRD. Additional studies are needed to establish the utility and cost-effectiveness of these novel biomarkers in the clinical setting.

Authors+Show Affiliations

Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom; Helen.alderson@manchester.ac.uk.Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom.Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland; and.Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom.Division of Nephrology and Hypertension, Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland; and.Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom.

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

27852662

Citation

Alderson, Helen V., et al. "The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin With Progression From CKD to ESRD." Clinical Journal of the American Society of Nephrology : CJASN, vol. 11, no. 12, 2016, pp. 2141-2149.
Alderson HV, Ritchie JP, Pagano S, et al. The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin with Progression from CKD to ESRD. Clin J Am Soc Nephrol. 2016;11(12):2141-2149.
Alderson, H. V., Ritchie, J. P., Pagano, S., Middleton, R. J., Pruijm, M., Vuilleumier, N., & Kalra, P. A. (2016). The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin with Progression from CKD to ESRD. Clinical Journal of the American Society of Nephrology : CJASN, 11(12), 2141-2149.
Alderson HV, et al. The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin With Progression From CKD to ESRD. Clin J Am Soc Nephrol. 2016 12 7;11(12):2141-2149. PubMed PMID: 27852662.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin with Progression from CKD to ESRD. AU - Alderson,Helen V, AU - Ritchie,James P, AU - Pagano,Sabrina, AU - Middleton,Rachel J, AU - Pruijm,Menno, AU - Vuilleumier,Nicolas, AU - Kalra,Philip A, Y1 - 2016/11/16/ PY - 2016/03/10/received PY - 2016/08/10/accepted PY - 2016/11/18/pubmed PY - 2017/12/2/medline PY - 2016/11/18/entrez KW - Acute-Phase Proteins KW - Adult KW - Biomarkers KW - KIM-1 KW - Kidney Failure, Chronic KW - LCN2 protein, human KW - Lipocalins KW - NGAL KW - Proto-Oncogene Proteins KW - ROC Curve KW - biomarkers KW - clinical outcomes KW - follow-up studies KW - humans KW - renal dialysis KW - renal insufficiency, chronic KW - risk factors KW - risk prediction SP - 2141 EP - 2149 JF - Clinical journal of the American Society of Nephrology : CJASN JO - Clin J Am Soc Nephrol VL - 11 IS - 12 N2 - BACKGROUND AND OBJECTIVES: Elevated levels of urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are associated with negative outcomes in CKD. Our study aimed to explore the prognostic accuracy of blood levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin for progression to ESRD, major adverse cardiovascular events, and death in a large cohort of adult patients with all-cause nondialysis-dependent CKD stages 3-5. We considered whether these factors improve prediction in relation to traditional biomarkers and clinical parameters. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were measured on baseline plasma samples from 1982 patients who were recruited to the Chronic Renal Insufficiency Standards Implementation Study between the start of June of 2002 and the start of June of 2013. Associations with study end points were assessed using Cox regression models, receiver operator characteristic curve analyses, and reclassification statistics. RESULTS: Over a median follow-up of 29.5 months (interquartile range, 14.9-53.5), 21.6% of patients progressed to ESRD, 27% died, and 6.6% suffered a major adverse cardiovascular event. Higher blood levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were independently associated with a greater risk for ESRD (hazard ratio, 1.25; 95% confidence interval, 1.10 to 1.43; P<0.001 and hazard ratio, 1.35; 95% confidence interval, 1.14 to 1.59; P≤0.001, respectively, per 1 SD higher biomarker concentration). There was no association with risk for cardiovascular events or death. The addition of biomarkers to our baseline risk model of traditional clinical characteristics and laboratory parameters did not significantly improve model discrimination or risk reclassification. CONCLUSIONS: In patients with moderate to severe CKD, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin blood levels are independent risk factors for progression to ESRD. Additional studies are needed to establish the utility and cost-effectiveness of these novel biomarkers in the clinical setting. SN - 1555-905X UR - https://www.unboundmedicine.com/medline/citation/27852662/The_Associations_of_Blood_Kidney_Injury_Molecule_1_and_Neutrophil_Gelatinase_Associated_Lipocalin_with_Progression_from_CKD_to_ESRD_ L2 - https://cjasn.asnjournals.org/cgi/pmidlookup?view=long&amp;pmid=27852662 DB - PRIME DP - Unbound Medicine ER -