Clinical outcome of renal tubular damage in chronic heart failure

Kevin Damman, Serge Masson, Hans L. Hillege, Aldo P. Maggioni, Adriaan A. Voors, Cristina Opasich, Dirk J. Van Veldhuisen, Laura Montagna, Franco Cosmi, Gianni Tognoni, Luigi Tavazzi, Roberto Latini

Research output: Contribution to journalArticle

Abstract

Aims Both reduced glomerular filtration and increased urinary albumin excretion independently determine outcome in patients with chronic heart failure (HF). However, tubulo-interstitial injury might indicate renal damage, even in the presence of normal glomerular filtration. We studied the relationship between tubular damage, glomerular filtration, urinary albumin excretion, and outcome in HF patients. Methods and results In 2130 patients participating in the GISSI-HF trial, we measured urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and three urinary markers of tubular damage: N-acetyl-beta-d-glucosaminidase (NAG), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL). We assessed the relationship between the individual tubular damage markers and the combined endpoint of all-cause mortality and HF hospitalizations. Mean age was 67 ± 11 years, and 21 were female. Urinary NAG 13.7 (7.822) U/gCr, KIM-1 1939 (6713871) ng/gCr, and NGAL 36 (1494) g/gCr were markedly elevated above normal levels. All individual tubular markers were independently associated with the combined endpoint: NAG: adjusted hazard ratio (HR) 1.22; 95 confidence interval (CI), 1.101.36; P<0.001, KIM-1 HR 1.13; 95 CI, 1.021.24; P = 0.018 and NGAL HR 1.10; 95 CI, 1.001.20; P = 0.042; all per log standard deviation increase). Even in patients with a normal eGFR, increased tubular markers were related to a poorer outcome. The combination of impaired eGFR, increased UACR, and high NAG was associated with a HR of 3.00; 95 CI, 2.293.95; P<0.001, compared with those without these abnormalities. Conclusion Tubular damage is related to a poor clinical outcome in HF patients even when eGFR is normal.ClinicalTrials.gov Identifier: NCT00336336 (for the main study).

Original languageEnglish
Pages (from-to)2705-2712
Number of pages8
JournalEuropean Heart Journal
Volume32
Issue number21
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Heart failure
  • Prognosis
  • Renal function
  • Tubular damage

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Damman, K., Masson, S., Hillege, H. L., Maggioni, A. P., Voors, A. A., Opasich, C., Van Veldhuisen, D. J., Montagna, L., Cosmi, F., Tognoni, G., Tavazzi, L., & Latini, R. (2011). Clinical outcome of renal tubular damage in chronic heart failure. European Heart Journal, 32(21), 2705-2712. https://doi.org/10.1093/eurheartj/ehr190