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.