Urinary levels of novel kidney biomarkers and risk of true worsening renal function and mortality in patients with acute heart failure

Eur J Heart Fail. 2017 Jun;19(6):760-767. doi: 10.1002/ejhf.746. Epub 2017 Jan 30.

Abstract

Aims: Recent studies indicate the need to redefine worsening renal function (WRF) in acute heart failure (AHF), linking a rise in creatinine with clinical status to identify patients who develop 'true WRF'. We evaluated the usefulness of serial assessment of urinary levels of neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (uKIM-1), and cystatin C (uCysC) for prediction of 'true WRF'.

Methods and results: In 132 patients with AHF, uNGAL, uKIM-1, and uCysC were measured using a highly sensitive immunoassay based on a single-molecule counting technology (Singulex, Alameda, CA, USA) at baseline, day 2, and day 3. Patients who developed WRF (a ≥0.3 mg/dL increase in serum creatinine or a >25% decrease in the estimated glomerular filtration rate from the baseline value) were differentiated into those 'true WRF' (presence of deterioration/no improvement in clinical status during hospitalization) vs. 'pseudo-WRF' (uneventful clinical course). 'True WRF' occurred in 13 (10%), 'pseudo-WRF' in 15 (11%), whereas the remaining 104 (79%) patients did not develop WRF. Patients with 'true WRF' were more often females, had higher levels of NT-proBNP, creatinine, and urea on admission, higher urine albumin to creatinine ratio at day 2, higher uNGAL at baseline, day 2, and day 3, and higher KIM-1 at day 2 (vs. pseudo-WRF vs. without WRF, all P < 0.05). Patients with pseudo-WRF did not differ from those without WRF. In the multivariable model, elevated uNGAL at all time points and uKIM-1 at day 2 remained independent predictors of 'true WRF'.

Conclusion: Elevated levels of uNGAL and uKIM-1 may predict development of 'true WRF' in AHF.

Keywords: Acute heart failure; Cystatin C; Kidney injury molecule-1; Neutrophil gelatinase-associated lipocalin; Urinary biomarkers; Worsening renal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Biomarkers / urine
  • Cystatin C / urine*
  • Disease Progression
  • Female
  • Glomerular Filtration Rate / physiology*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Heart Failure / urine*
  • Hepatitis A Virus Cellular Receptor 1 / metabolism*
  • Humans
  • Immunoassay
  • Kidney / physiopathology*
  • Kidney Function Tests
  • Lipocalin-2 / urine*
  • Male
  • Poland / epidemiology
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Renal Insufficiency, Chronic / etiology
  • Renal Insufficiency, Chronic / physiopathology
  • Renal Insufficiency, Chronic / urine*

Substances

  • Biomarkers
  • Cystatin C
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • LCN2 protein, human
  • Lipocalin-2