title: Clinical outcome of renal tubular damage in chronic heart failure.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Tubular damage is related to a poor clinical outcome in HF patients even when eGFR is normal.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. k.damman@thorax.umcg.nl
authors.forename: Kevin
authors.initials: K
authors.lastname: Damman
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.forename: Cristina
authors.initials: C
authors.lastname: Opasich
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Laura
authors.initials: L
authors.lastname: Montagna
authors.forename: Franco
authors.initials: F
authors.lastname: Cosmi
authors.forename: Gianni
authors.initials: G
authors.lastname: Tognoni
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine; D000368:Aged; D000419:Albuminuria; D059347:Cardio-Renal Syndrome / Q000503:physiopathology* / Q000652:urine; D002908:Chronic Disease; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007684:Kidney Tubules / Q000503:physiopathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011518:Proto-Oncogene Proteins / Q000652:urine; D016032:Randomized Controlled Trials as Topic; D011991:Receptors, Virus
chemical_list: D000209:Acute-Phase Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D000118:Acetylglucosaminidase