Neutrophil gelatinase-associated lipocalin as a marker of tubular damage appears to be unrelated to fractional excretion of sodium as a marker of tubular function in septic patients, with or without AKI

Nj Glassford,L Peck,R Bellomo,H Young,G Eastwood,Ag Schneider

doi:10.1186/cc10379

Abstract

The utility of urinary biochemistry has recently been challenged [1], while there is emerging evidence that renal biomarkers may accurately quantify the risk of development of acute kidney injury (AKI) [2]. Neutrophil gelatinase-associated lipocalin (NGAL) is a marker of renal tubular damage [3]. Fractional excretion of sodium (FENa) is a marker of renal tubular function, and is a significantly cheaper investigation [4]. Insults damaging the tubules and resulting in AKI should both stimulate NGAL production and prevent resorption of sodium. Given the different pathological mechanisms underlying septic and nonseptic AKI, it is plausible that the relationship between these variables could be different in these two groups of patients [5].

Highlights

Fibrinolytic shutdown plays a pivotalrole in the pathogenesis of multiple organ dysfunction syndrome (MODS) in disseminated intravascular coagulation (DIC)
Beneficial action is mainly believed through improvement of major antioxidant selenoenzymes, but could on the contrary be related to a therapeutic oxidant action reducing activity of hyperactivated circulating phagocytic cells [4]
It has been suggested that the absence of beneficial effect of high-dose Na SeO continuously administered [2] might be related to toxicity, especially on the lung, of too much selenium (Se) as mentioned in recent parenteral nutrition guidelines in intensive care

Summary

Introduction

Fibrinolytic shutdown plays a pivotalrole in the pathogenesis of multiple organ dysfunction syndrome (MODS) in disseminated intravascular coagulation (DIC). In a separate set of experiments investigating the MOA, AB103 administration (5 mg/kg, given without antibiotics 2 hours post CLP) was associated with: a reduction in Th-1 cytokine levels in peritoneum (TNFα, IL-3, IL-17 and Rantes) and plasma (IL-3 and IL-6); a reduction in splenocyte proliferation, stimulated ex vivo with anti-CD3 and anti-CD28 antibodies; a reduction in neutrophil recruitment to the spleen, liver and kidney, as determined by MPO activity; and a reduced bacterial load in peritoneum, blood and tissues (kidney, liver, spleen) Conclusion These data demonstrate that attenuation of CD28 signaling is a viable therapeutic approach to the treatment of sepsis. Therapeutic dosing of AZD9773 bid from 24 to 60 hours (schedule/dose/route as previously) did not result in significantly different survival outcomes versus either DigiFab or imipenem alone (n = 60 per group) Conclusion These data demonstrate for the first time that TNFα neutralization in a murine CLP model improves survival in a severe sepsis setting.

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Conclusion