title: Urinary levels of novel kidney biomarkers and risk of true worsening renal function and mortality in patients with acute heart failure.
abstract: 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'.
  
  
  
  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'.
  
  
  
  Elevated levels of uNGAL and uKIM-1 may predict development of 'true WRF' in AHF.
authors.affiliation: Wroclaw Medical University, Department of Heart Diseases, Wroclaw, Poland.|Centre for Heart Disease, Clinical Military Hospital, Wroclaw, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Sokolski
authors.affiliation: Centre for Heart Disease, Clinical Military Hospital, Wroclaw, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Zymliński
authors.affiliation: Wroclaw Medical University, Department of Heart Diseases, Wroclaw, Poland.|Centre for Heart Disease, Clinical Military Hospital, Wroclaw, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Biegus
authors.affiliation: Centre for Heart Disease, Clinical Military Hospital, Wroclaw, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Siwołowski
authors.affiliation: Centre for Heart Disease, Clinical Military Hospital, Wroclaw, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Nawrocka-Millward
authors.affiliation: Singulex, Inc., Alameda, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Todd
authors.affiliation: Singulex, Inc., Alameda, CA, USA.
authors.forename: Malli Rama
authors.initials: MR
authors.lastname: Yerramilli
authors.affiliation: Singulex, Inc., Alameda, CA, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Estis
authors.affiliation: Centre for Heart Disease, Clinical Military Hospital, Wroclaw, Poland.|Wroclaw Medical University, Laboratory for Applied Research on Cardiovascular System, Department of Heart Diseases, Wroclaw, Poland.
authors.forename: Ewa Anita
authors.initials: EA
authors.lastname: Jankowska
authors.affiliation: Centre for Heart Disease, Clinical Military Hospital, Wroclaw, Poland.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Banasiak
authors.affiliation: Wroclaw Medical University, Department of Heart Diseases, Wroclaw, Poland.|Centre for Heart Disease, Clinical Military Hospital, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000652:urine; D055316:Cystatin C / Q000652:urine*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006333:Heart Failure / Q000401:mortality / Q000503:physiopathology / Q000652:urine*; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism*; D006801:Humans; D007118:Immunoassay; D007668:Kidney / Q000503:physiopathology*; D007677:Kidney Function Tests; D000071068:Lipocalin-2 / Q000652:urine*; D008297:Male; D011044:Poland / Q000453:epidemiology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000503:physiopathology / Q000652:urine*
chemical_list: D015415:Biomarkers; D055316:Cystatin C; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2
keywords: Acute heart failure; Cystatin C; Kidney injury molecule-1; Neutrophil gelatinase-associated lipocalin; Urinary biomarkers; Worsening renal function