Document Detail


Tubular damage in chronic systolic heart failure is associated with reduced survival independent of glomerular filtration rate.
MedLine Citation:
PMID:  20659949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The prognostic impact of reduced glomerular filtration rate (GFR) in chronic heart failure (CHF) is increasingly recognised, but little is known about tubular damage in these patients.
OBJECTIVE: To investigate the prevalence of tubular damage, and its association with GFR, and prognosis in patients with CHF.
METHODS AND RESULTS: In 90 patients with CHF, GFR and effective renal plasma flow (ERPF) were measured ([(125)I]iothalamate and [(131)I]hippuran clearances). The tubular markers neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1) as well as urinary albumin excretion were determined in 24 h urine collections. Mean GFR was 78+/-26 ml/min/1.73 m(2). Urinary NGAL (175 (70-346) microg/g creatinine (gCr)), NAG (12 (6-17) U/gCr) and KIM-1 (277 (188-537) ng/gCr) levels were increased compared with 20 healthy controls (all p<0.001). Urinary NAG, but not NGAL or KIM-1 correlated with GFR (r=-0.34, p=0.001) and ERPF (r=-0.29, p=0.006). Both NAG (r=0.21, p=0.048) and KIM-1 (r=0.23, p=0.033) correlated with plasma N-terminal pro-brain natriuretic peptide levels. Both urinary KIM-1 (HR=1.15 (95% CI 1.02 to 1.30) per 100 ng/gCr increase, p=0.025) and NAG (HR=1.42 (95% CI 1.02 to 1.94) per 5 U/gCr increase, p=0.039), were associated with an increased risk of death or heart failure hospitalisations, independent of GFR.
CONCLUSION: Tubular damage, as indicated by increased urinary concentrations of NGAL, NAG and KIM-1 is common in patients with CHF and mildly reduced GFR. Both urinary KIM-1 and NAG showed prognostic information additional to GFR. These findings suggest an important role for tubular damage and tubular markers in cardiorenal interaction in heart failure.
Authors:
Kevin Damman; Dirk J Van Veldhuisen; Gerjan Navis; Vishal S Vaidya; Tom D J Smilde; B Daan Westenbrink; Joseph V Bonventre; Adriaan A Voors; Hans L Hillege
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Heart (British Cardiac Society)     Volume:  96     ISSN:  1468-201X     ISO Abbreviation:  Heart     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-27     Completed Date:  2010-08-19     Revised Date:  2013-02-19    
Medline Journal Info:
Nlm Unique ID:  9602087     Medline TA:  Heart     Country:  England    
Other Details:
Languages:  eng     Pagination:  1297-302     Citation Subset:  AIM; IM    
Affiliation:
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Biological Markers / blood,  urine
Chronic Disease
Epidemiologic Methods
Female
Glomerular Filtration Rate / physiology
Heart Failure, Systolic / complications*,  mortality,  physiopathology
Humans
Kidney Diseases / etiology*,  mortality,  physiopathology
Kidney Tubules / physiopathology*
Male
Middle Aged
Prognosis
Renal Circulation / physiology
Young Adult
Grant Support
ID/Acronym/Agency:
DK39773/DK/NIDDK NIH HHS; DK74099/DK/NIDDK NIH HHS; R00 ES016723-03S1/ES/NIEHS NIH HHS; R00 ES016723-04/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers
Comments/Corrections

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