Clinical outcome of renal tubular damage in chronic heart failure

Eur Heart J. 2011 Nov;32(21):2705-12. doi: 10.1093/eurheartj/ehr190. Epub 2011 Jun 11.


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 (7.8-22) U/gCr, KIM-1 1939 (671-3871) ng/gCr, and NGAL 36 (14-94) µg/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), 1.10-1.36; P< 0.001, KIM-1 HR 1.13; 95% CI, 1.02-1.24; P= 0.018 and NGAL HR 1.10; 95% CI, 1.00-1.20; 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, 2.29-3.95; 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.

Trial registration: NCT00336336.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / urine
  • Acute-Phase Proteins / urine
  • Aged
  • Albuminuria
  • Cardio-Renal Syndrome / physiopathology*
  • Cardio-Renal Syndrome / urine
  • Chronic Disease
  • Female
  • Glomerular Filtration Rate / physiology
  • Hepatitis A Virus Cellular Receptor 1
  • Humans
  • Kidney Tubules / physiopathology*
  • Lipocalin-2
  • Lipocalins / urine
  • Male
  • Membrane Glycoproteins / urine
  • Middle Aged
  • Multicenter Studies as Topic
  • Proto-Oncogene Proteins / urine
  • Randomized Controlled Trials as Topic
  • Receptors, Virus


  • Acute-Phase Proteins
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins
  • Receptors, Virus
  • Acetylglucosaminidase

Associated data