The Role of the Mesencephalic Astrocyte-Derived Neurotrophic Factor in Patients in Intensive Care Units Receiving Voriconazole Therapy.

Abstract

Recent publications regarding the role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in various metabolic and degenerative disorders suggest that MANF is both a marker of disease and a possible therapeutic agent. We investigate the role of plasma MANF levels in patients in intensive care units (ICUs) receiving voriconazole (VCZ) therapy while also comparing MANF levels in healthy individuals. A single-center prospective study was conducted. The plasma MANF level in patients in ICU was found to have high interindividual variability and was significantly higher than that in healthy controls (P<.01). Compared with patients using VCZ only, patients using both VCZ and amikacin had 3-fold lower MANF concentrations (P<.05). The MANF concentrations also decreased when alkaline phosphatase (ALP) and serum creatinine levels were above the upper limits of the normal range (P<.05) and the estimated glomerular filtration rate (eGFR) was below the lower limit of the normal range (P<.01). Receiver operating characteristic curve analysis indicated that low MANF levels were associated with high ALP levels, high creatinine levels, and low eGFR. The cut-off value of MANF for ALP levels higher than 126U/L was 0.35ng/mL (area under curve, AUC=0.62, 95%CI=0.50-0.74, P=.044); for serum creatinine levels higher than 104μmol/L, the cut-off value was 0.41ng/mL (AUC=0.74, 95%CI=0.62-0.87, P=.001); and for eGFR below 80mL/min, the cut-off value was 0.75ng/mL (AUC=0.70, 95%CI=0.59-0.81, P=.002). Monitoring plasma MANF levels may be of value for clinical decision-making regarding the choice of antibiotics and the prediction of impaired liver function and renal function in patients admitted to an ICU.