Plasma kidney injury molecule-1 in heart failure: renal mechanisms and clinical outcome

Emmens, J. E. et al. (2016) Plasma kidney injury molecule-1 in heart failure: renal mechanisms and clinical outcome. European Journal of Heart Failure, 18(6), pp. 641-649. (doi: 10.1002/ejhf.426) (PMID:26511274)

Abstract

Aims: Urinary kidney injury molecule-1 (KIM-1) is a marker of tubular damage and associated with worse outcome in heart failure (HF). Plasma KIM-1 has not been described in HF. Methods and results: In a renal mechanistic cohort of 120 chronic HF patients, we established the association between plasma KIM-1, renal invasive haemodynamic parameters {renal blood flow ([131I]hippuran clearance) and measured glomerular filtration rate (GFR; [125I]iothalamate)} and urinary tubular damage markers. The association between plasma KIM-1, plasma creatinine, and clinical outcome was further explored in a cohort of 2033 acute HF patients. Median plasma KIM-1 was 171.5 pg/mL (122.8–325.7) in chronic (n = 99) and 295.1 pg/mL (182.2–484.2) in acute HF (n = 1588). In chronic HF, plasma KIM-1 was associated with GFR (P < 0.001), creatinine, and cystatin C. Plasma KIM-1 was associated with urinary N-acetyl-β-d-glucosaminidase (NAG), but not with other urinary tubular damage markers. Log plasma KIM-1 predicted adverse clinical outcome after adjustment for age, gender, and GFR [hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.07–3.53, P = 0.030]. Statistical significance was lost after correction for NT-proBNP (HR 1.61, 95% CI 0.81–3.20, P = 0.175). In acute HF, higher plasma KIM-1 levels were associated with higher creatinine, lower albumin, and presence of diabetes. Log plasma KIM-1 predicted 60-day HF rehospitalization (HR 1.27, 95% CI 1.03–1.55, P = 0.024), but not 180-day mortality or 60-day death or renal or cardiovascular rehospitalization. Conclusions: Plasma KIM-1 is associated with glomerular filtration and urinary NAG, but not with other urinary tubular damage markers. Plasma KIM-1 does not predict outcome in chronic HF after correction for NT-proBNP. In acute HF, plasma KIM-1 predicts HF rehospitalization in multivariable analysis.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cleland, Professor John
• Authors: Emmens, J. E., ter Maaten, J. M., Matsue, Y., Metra, M., O'Connor, C. M., Ponikowski, P., Teerlink, J. R., Cotter, G., Davison, B., Cleland, J. G.F., Givertz, M. M., Bloomfield, D. M., Dittrich, H. C., Todd, J., van Veldhuisen, D. J., Hillege, H. L., Damman, K., van der Meer, P., and Voors, A. A.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 28 October 2015
• Copyright Holders: Copyright © 2016 European Society of Cardiology
• First Published: First published in European Journal of Heart Failure 18(6): 641-649
• Publisher Policy: Reproduced in accordance with the publisher copyright policy