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Plasma neutrophil gelatinase-associated lipocalin is independently associated with left ventricular hypertrophy and diastolic dysfunction in patients with chronic kidney disease.

ABSTRACT: BACKGROUND:Cardiovascular disease (CVD) is a leading cause of death in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are known as predictors of CVD in these patients. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury. Recently, elevated NGAL levels have been reported in patients with CVD. This study aimed to evaluate the association between plasma NGAL levels and LVH/LVDD in patients with CKD. METHODS:This study included 332 patients with pre-dialysis CKD (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2). Two-dimensional echocardiography was performed to measure the left ventricular mass index (LVMI). Tissue Doppler imaging was used to measure early mitral inflow velocity (E) and the peak early mitral annular velocity (E'). Diastolic function was estimated using E' and the ratio of E to E' (E/E'). The associations of echocardiographic index with clinical and laboratory variables (age, sex, diabetes, hypertension, eGFR, albumin, uric acid, calcium, phosphate, total cholesterol, hemoglobin, C-reactive protein, intact parathyroid hormone (PTH), the inferior vena cava collapse index (IVCCI) < 50%, and plasma NGAL) were investigated using univariate and multivariate analyses. RESULTS:In multivariate logistic regression analysis, plasma NGAL was an independent predictor of LVH (OR: 1.02, 95% CI: 1.01-1.02), P < 0.001). In addition, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVH. Plasma NGAL (OR: 1.02, 95% CI: 1.01-1.02, P < 0.001) was also an independent factor of LVDD. Furthermore, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVDD. Receiver operating characteristic curve analysis (area under the curve: 0.835, 95% CI: 0.792-0.879) showed the best cutoff value of plasma NGAL for identifying LVDD was ? 258 ng/ml with an associated sensitivity of 77.6% and a specificity of 87.6%. CONCLUSION:Plasma NGAL levels were independent predictors of LVH and LVDD in patients with pre-dialysis CKD, suggesting that plasma NGAL could be a biomarker for LVH and LVDD in these patients.

SUBMITTER: Kim IY

PROVIDER: S-EPMC6191140 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Plasma neutrophil gelatinase-associated lipocalin is independently associated with left ventricular hypertrophy and diastolic dysfunction in patients with chronic kidney disease.

Kim Il Young IY Kim June Hyun JH Kim Min Jeong MJ Lee Dong Won DW Hwang Cheol Gu CG Han Miyeun M Rhee Harin H Song Sang Heon SH Seong Eun Young EY Lee Soo Bong SB

PloS one 20181016 10

<h4>Background</h4>Cardiovascular disease (CVD) is a leading cause of death in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are known as predictors of CVD in these patients. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury. Recently, elevated NGAL levels have been reported in patients with CVD. This study aimed to evaluate the association between plasma NGAL levels and LVH/L ...[more]

PMID: 30325973

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Project description:AimsConcentric hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the concentrically hypertrophied heart following pressure-overload.Methods and resultsRats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular concentric hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e' values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+].ConclusionIn the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis.

Dataset Information

Plasma neutrophil gelatinase-associated lipocalin is independently associated with left ventricular hypertrophy and diastolic dysfunction in patients with chronic kidney disease.

Publications

Plasma neutrophil gelatinase-associated lipocalin is independently associated with left ventricular hypertrophy and diastolic dysfunction in patients with chronic kidney disease.

Similar Datasets

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