NGAL in Sepsis

Severe sepsis is a major cause of mortality and morbidity, with a mortality rate of 35%. Claiming between 36000 and 64000 lives annually in the UK, more people die from sepsis than lung cancer and more than from breast cancer and
bowel cancer combined.

Research shows that early recognition and intervention saves lives and could prevent as many as 15000 deaths annually in the UK.

sepsis-mortality-UK
Chart showing relative mortality figures in one year for the UK for common conditions*.

The incidence of severe sepsis is increasing as our population ages. The host response determines the severity of the infection rather than the organism responsible. Severe cases are characterised by  overzealous activation of the host’s innate immune system (all functions except the T and B cells) resulting in activation of the coagulation cascade, inflammation, systemic vasodilatation, increased capillary permeability, end organ dysfunction and, ultimately, multi-organ failure and death.

Sepsis frequently results in acute kidney injury (AKI). Around 48% of AKI cases in Intensive Therapy Units (ITU) are thought to be caused by sepsis. Although AKI markedly contributes to mortality in sepsis, its diagnosis is frequently delayed due to limitations of current biomarkers of renal impairment.

Creatinine has been the traditional indicator of AKI but is a marker of function rather than of injury, often delaying identification of AKI and initiation of a clinical response. Neutrophil Gelatinase-associated Lipocalin (NGAL) has been demonstrated to be a biomarker of early AKI and its use could improve the outcome of many patients with sepsis.

Identification of the cause of renal impairment is particularly important since acute septic renal injury results in markedly worse prognosis, classification as severe sepsis and intensified monitoring in an ITU. In contrast, stable chronic renal impairment in patients would be a comparatively minor risk factor for a poor prognosis. Septic AKI patients have higher plasma and urine NGAL concentrations compared with nonseptic AKI patients.

More sensitive detection of AKI (NGAL+, creatinine-) would result in staging as “severe sepsis” instead of sepsis without other organ failure. Early detection of AKI might help to allocate additional curative (antimicrobial therapy, intervention) and supportive measures for sepsis, as well as specific initiatives to prevent further renal damage. Changing the clinical responses according to significant predictors and avoidance of further renal impairment carries a high potential for cost effectiveness as emphasised by a number of studies.

References

* Sources:

Sepsis, ICNARC data 2006.

For all others: for England and Wales: Office for National Statistics 2008, for Scotland: General Register Office Registrar General Annual Report 2008, and for Northern Ireland: Statistics and Research Agency Registrar General Annual Report 2008.

This article was published previously in Alpha Laboratories’ Leading Edge Newsletter – Winter 2012.

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