1. Patient-specific evolution of renal function in chronic heart failure patients dynamically predicts clinical outcome in the Bio-SHiFT study
- Author
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Dimitris Rizopoulos, Sharda S. Anroedh, Olivier C. Manintveld, Isabella Kardys, Kadir Caliskan, Victor A. Umans, Hans L. Hillege, Jan H. Cornel, Alina A. Constantinescu, Milos Brankovic, Nick van Boven, K. Martijn Akkerhuis, Eric Boersma, Sara J. Baart, Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Cardiology, and Epidemiology
- Subjects
Male ,CHRONIC KIDNEY-DISEASE ,Time Factors ,medicine.medical_treatment ,temporal evolution ,heart failure ,030204 cardiovascular system & hematology ,Kidney ,COLLABORATION ,GUIDELINES ,Ventricular Function, Left ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Cause of Death ,030212 general & internal medicine ,Prospective Studies ,Netherlands ,Heart transplantation ,Aged, 80 and over ,Ejection fraction ,biology ,Hazard ratio ,dynamic prediction ,Middle Aged ,EUROPEAN-SOCIETY ,Hospitalization ,Treatment Outcome ,Nephrology ,Cardiology ,Disease Progression ,individual risk ,Female ,Kidney Diseases ,Glomerular Filtration Rate ,tubular markers ,medicine.medical_specialty ,Urinary system ,BIOMARKERS ,Renal function ,DIAGNOSIS ,EJECTION FRACTION ,03 medical and health sciences ,Predictive Value of Tests ,Internal medicine ,renal dysfunction ,medicine ,INJURY ,Humans ,Aged ,Creatinine ,TUBULAR DAMAGE ,business.industry ,Stroke Volume ,medicine.disease ,DYSFUNCTION ,Endocrinology ,Cystatin C ,chemistry ,Heart failure ,biology.protein ,Heart Transplantation ,Heart-Assist Devices ,business - Abstract
Renal dysfunction is an important component of chronic heart failure (CHF), but its single assessment does not sufficiently reflect clinically silent progression of CHF prior to adverse clinical outcome. Therefore, we aimed to investigate temporal evolutions of glomerular and tubular markers in 263 stable patients with CHF, and to determine if their patient-specific evolutions during this clinically silent period can dynamically predict clinical outcome. We determined the risk of clinical outcome (composite endpoint of Heart Failure hospitalization, cardiac death, Left Ventricular Assist Device placement, and heart transplantation) in relation to marker levels, slopes and areas under their trajectories. In each patient, the trajectories were estimated using repeatedly measured glomerular markers: creatinine/estimated glomerular filtration rate (eGFR), cystatin C (CysC), and tubular markers: urinary N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule (KIM)-1, plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL). During 2.2 years of follow-up, we collected on average 8 urine and 9 plasma samples per patient. All glomerular markers predicted the endpoint (univariable hazard ratio [95% confidence interval] per 20% increase: creatinine: 1.18 [1.07-1.31], CysC: 2.41[ 1.81-3.41], and per 20% eGFR decrease: 1.13[1.05-1.23]). Tubular markers, NAG, and KIM-1 also predicted the endpoint (NAG: 1.06[1.01-1.11] and KIM-1: 1.08[1.04-1.11]). Larger slopes were the strongest predictors (creatinine: 1.57[1.39-1.84], CysC: 1.76 [1.52-2.09], eGFR: 1.59[1.37-1.90], NAG: 1.26[1.11-1.44], and KIM-1: 1.64[1.38-2.05]). Associations persisted after multivariable adjustment for clinical characteristics. Thus, during clinically silent progression of CHF, glomerular and tubular functions deteriorate, but not simultaneously. Hence, patient-specific evolutions of these renal markers dynamically predict clinical outcome in patients with CHF.
- Published
- 2018