Biomarkers of Inflammation, Fibrosis, and Acute Kidney Injury in Patients with Heart Failure with and without Left Ventricular Assist Device Implantation

Abstract

Background/Aims: Renal dysfunction or renal failure is a common complication in left ventricular assist device (LVAD) recipients and is associated with reduced survival. To date, serum creatinine and glomerular filtration rate (GFR) are used for the evaluation of kidney function. However, serum creatinine and GFR have limitations. The objective of our study is to assess the levels of kidney biomarkers in LVAD recipients compared to heart failure patients and healthy controls and to examine their association with conventional clinical biomarkers. Methods: The biomarkers neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), plasminogen activator inhibitor-1 (PAI-1), and adiponectin were assessed in 51 participants: 19 heart failure patients, 16 LVAD recipients, and 16 healthy controls. Linear regressions were performed to assess whether demographic and clinical variables predict the levels of biomarkers that are associated with acute kidney injury and the risk of chronic kidney disease. Results: The levels of NGAL and adiponectin were higher in LVAD recipients and patients with heart failure as compared with healthy controls. The levels of PAI-1 and KIM-1 were not elevated in LVAD recipients. The results of linear regression analysis indicated that when controlling for the effect of CRP and BNP, 40.1% of the variance in NGAL levels can be explained by GFR (R² = 0.401, F = 5.56, p = 0.005), while CRP can explain 35.3% of the variance in adiponectin levels (R² = 0.353, F = 4.55, p = 0.01), when controlling for the effect of BNP and GFR. Conclusions: The levels of NGAL and adiponectin were augmented in LVAD recipients, suggesting that renal functions were not restored with circulatory support. Larger studies should assess the predictability of these biomarkers of renal dysfunction in LVAD recipients.

Elevated urinary Kidney Injury Molecule 1 (KIM-1) at discharge strongly predicts early mortality following an episode of acute decompensated heart failure

“…In GISSI-HF study, a prospective study of a large chronic heart failure (CHF) cohort [20], NGAL also predicted worsening of renal function. Our results, however, are consistent with those of more recent and larger cohort studies [21][22][23][24][25] that show poor, or no, AKI diagnostic value for serum NGAL.…”

“…A recent analysis of urine NGAL levels in the AKINESIS cohort yielded similar results [27]. The fact that serum NGAL concentrations are primarily determined by renal function would explain NGAL's poor predicting ability in AKI [25,28], as demonstrated also by our own findings. On the other hand, intensive diuretic therapy used during the active decongestion phase appears to dissociate changes in serum and urine NGAL from those in renal function markers.…”

Oncostatin M: a Potential Biomarker to Predict Infection in Patients with Left Ventricular Assist Devices

“…[2][3][4][5] Predictors for risk of infection in LVAD recipients have been sought but to date remain unreliable. 6,7 We hypothesized that plasma Oncostatin M (OSM), a sensitive indicator of an activated state of inflammation, could be predictive of infections in LVAD recipients. This cytokine, a member of the interleukin-6 family, was first purified in phorbol-12-myristate-13-acetate-treated histiocytic lymphoma cell line, U-937.…”

“…Given that, we hypothesized that an increase in plasma OSM levels could serve as a more sensitive predictor of infection risk than previously proposed biomarkers. 6,7 To test this hypothesis, we performed serial measurements of plasma OSM levels before LVAD implantation and for two months following. We then studied the relationship between OSM levels and the development of postoperative infection.…”

“…Given that, we hypothesized that an increase in plasma OSM levels could serve as a more sensitive predictor of infection risk than previously proposed biomarkers. 6,7…”