Plasma Neutrophil Gelatinase-Associated Lipocalin Is Primarily Related to Inflammation during Sepsis: A Translational Approach

Abstract

Acute kidney injury (AKI) during sepsis is common and underestimated. Plasma neutrophil gelatinase-associated lipocalin (plasma-NGAL) is discussed as new biomarker for AKI diagnosis, but during inflammation its function and diagnostic impact remain unclear. The association between plasma-NGAL and inflammatory markers in septic patients, but also in healthy controls and patients with chronic inflammation before and after either maximum exercise test or treatment with an anti-TNF therapy were investigated. In-vitro blood stimulations with IL-6, lipopolysaccharide, NGAL or its combinations were performed to investigate cause-effect-relationship. Plasma-NGAL levels were stronger associated with inflammation markers including IL-6 (Sepsis: r=0.785 P<0.001; chronic inflammation after anti-TNF: r=0.558 P<0.001), IL-8 (Sepsis: r=0.714 P<0.004; healthy controls after exercise r=0.786 P<0.028; chronic inflammation before anti-TNF: r=0.429 P<0.041) and IL-10 (healthy controls before exercise: r=0.791 P<0.028) than with kidney injury or function. Correlation to kidney injury or function was found only in septic patients (for creatinine: r= 0.906 P<0.001; for eGFR: r= -0.686 P=0.005) and in patients with rheumatic disease after anti-TNF therapy (for creatinine: r= 0.466 P<0.025). In stimulation assays with IL-6 and lipopolysaccharide plasma-NGAL was increased. Co-stimulation of lipopolysaccharide with plasma-NGAL decreased cellular injury (P<0.05) and in trend IL-10 levels (P=0.057). Septic mice demonstrated a significantly improved survival rate after NGAL treatment (P<0.01). Plasma-NGAL seams to be strongly involved in inflammation. For clinical relevance, it might not only be useful for AKI detection during severe inflammation - indeed it has to be interpreted carefully within this setting - but additionally might offer therapeutic potential.

Urinary exosomal activating transcriptional factor 3 as the early diagnostic biomarker for sepsis-induced acute kidney injury

“…Then ATF3 in urine should be a better representative renal biomarker than serum ATF3. NGAL, on the other hand, is also not specific to kidney and kidney injury [37] but it could be used as an early-AKI biomarker [14, 38, 39]. Although, the early expression of NGAL and ATF3 in kidney of CLP mice suggested the possibility of early sepsis biomarker, CLP model was anuria.…”

The impact of hydrocortisone treatment on neutrophil gelatinase-associated lipocalin release in porcine endotoxemic shock

“…No association between NGAL and renal function was seen. Others have also reported NGAL to be a marker of inflammatory response rather than to that of sepsis [24–26] and specifically pointed out that the origin of NGAL in systemic inflammatory response is neutrophil granulocytes [27]. Endotoxin induces this release of NGAL from these cells via the Toll-like receptor 4 (TLR-4) [28].…”

Intraoperative biomarkers in renal transplantation

“…In addition inflammatory biomarkers, for instance NGAL and IL‐18 are susceptible to various clinical conditions, such as bacterial‐mediated infectious processes, sepsis, cancer or preeclampsia and therefore need to be interpreted carefully in an overall clinical context …”

“…1 In addition inflammatory biomarkers, for instance NGAL and IL-18 are susceptible to various clinical conditions, such as bacterial-mediated infectious processes, sepsis, cancer or preeclampsia and therefore need to be interpreted carefully in an overall clinical context. [136][137][138] Other issues in the context of biomarker use and interpretation include their application-related significance. In AKI we know that the established biomarkers show an individual and time-dependent increase and decrease according to mechanisms of renal damage and function.…”