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Renal tubular damage and worsening renal function in chronic heart failure

Authors :
Jan van Ramshorst
Alina A. Constantinescu
Eric Boersma
Ewout J. Hoorn
Victor A. Umans
Milos Brankovic
Nick van Boven
Tjeerd Germans
Jan C. van den Berge
Jasper J. Brugts
K. Martijn Akkerhuis
Hans L. Hillege
Isabella Kardys
Life Course Epidemiology (LCE)
Groningen Kidney Center (GKC)
Cardiovascular Centre (CVC)
Cardiology
Internal Medicine
Source :
Clinical Cardiology, 43(6), 630-638. Wiley, Clinical Cardiology, Clinical Cardiology, 43(6), 630-638. Wiley-Blackwell
Publication Year :
2020

Abstract

Background It is uncertain that chronic heart failure (CHF) patients are susceptible to renal tubular damage with that of worsening renal function (WRF) preceding clinical outcomes.Hypothesis Changes in tubular damage biomarkers are stronger predictors of subsequent clinical events than changes in creatinine (Cr), and both have different clinical determinants.Methods During 2.2 years, we repeatedly simultaneously collected a median of 9 blood and 8 urine samples per patient in 263 CHF patients. We determined the slopes (rates of change) of the biomarker trajectories for plasma (Cr) and urinary tubular damage biomarkers N-acetyl-beta-d-glucosaminidase (NAG), and kidney-injury-molecule (KIM)-1. The degree of tubular injury was ranked according to NAG and KIM-1 slopes: increase in neither, increase in either, or increase in both; WRF was defined as increasing Cr slope. The composite endpoint comprised HF-hospitalization, cardiac death, left ventricular assist device placement, and heart transplantation.Results Higher baseline NT-proBNP and lower eGFR predicted more severe tubular damage (adjusted odds ratio, adj. OR [95%CI, 95% confidence interval] per doubling NT-proBNP: 1.26 [1.07-1.49]; per 10 mL/min/1.73 m(2) eGFR decrease 1.16 [1.03-1.31]). Higher loop diuretic doses, lower aldosterone antagonist doses, and higher eGFR predicted WRF (furosemide per 40 mg increase: 1.32 [1.08-1.62]; spironolactone per 25 mg decrease: 1.76 [1.07-2.89]; per 10 mL/min/1.73 m(2) eGFR increase: 1.40 [1.20-1.63]). WRF and higher rank of tubular injury individually entailed higher risk of the composite endpoint (adjusted hazard ratios, adj. HR [95%CI]: WRF 1.9 [1.1-3.4], tubular 8.4 [2.6-27.9]; when combined risk was highest 15.0 [2.0-111.0]).Conclusion Slopes of tubular damage and WRF biomarkers had different clinical determinants. Both predicted clinical outcome, but this association was stronger for tubular injury. Prognostic effects of both appeared independent and additive.

Details

Language :
English
ISSN :
01609289
Volume :
43
Issue :
6
Database :
OpenAIRE
Journal :
Clinical Cardiology
Accession number :
edsair.doi.dedup.....be27da55eea05b6459d4bc2de79e5131