NGAL as a novel biomarker of Acute Kidney Injury (AKI)

· TGI - Biomarkers, TGI - Health


Kidney (Photo credit: Joshua Schwimmer)

Acute kidney injury (AKI) is a common medical problem among critical patients. In current clinical practice, AKI is diagnosed by measuring serum creatinine concentration. Creatinine, as well as blood urea nitrogen (BUN) or urine markers of kidney injury (fractional excretion of sodium, urinary concentrating ability, casts), do not directly reflect cell injury. Serum creatinine concentration is considered as a delayed marker of the deterioration of kidney function because a significant amount of time is lost by the time these markers reach the detection levels.

Therefore an early diagnosis of AKI allows the early institution of therapeutic measures for the protection of renal function and improve the prognosis.

To identify an early stages of AKI there is a need to first identify sensitive and specific biomarkers. One such possibility seems to be ‘neutrophil gelatinase-associated lipocalin (NGAL)’. Now NGAL is emerging as a novel biomarker of AKI from several etiologies, such as:

cardiac surgery,

contrast nephropathy,

kidney transplantation and


This protein, produced in a number of human tissues and particularly in the distal nephron, has siderophore-chelating property and acts as an iron-trasporting shuttle.

NGAL increases in both serum and urine 48 hours before the rise of creatinine, and shows a strong correlation with change in creatinine concentrations. NGAL can be used as early marker of AKI and is particularly important in the Emergency Department.

The factors that are able to modify physiological levels are age, gender, ethnicity, dietary protein intake, muscle mass or metabolism, hydration status and drugs.

Another study, a meta-analysis, suggests that while serum creatinine level is used for AKI definition, NGAL level appears to be of diagnostic and prognostic value for AKI.

Further more, another study reviewed the data and suggests that neutrophil gelatinase-associated lipocalin (NGAL) is arguably the most promising novel AKI biomarker. It is emerging as an excellent standalone troponin-like biomarker in the plasma and urine for the prediction of AKI, monitoring clinical trials in AKI and for the prognosis of AKI in several common clinical scenarios. The results were published in journal Biomark Med. 2010 Apr;4(2):265-80.

Most recent study suggests that NGAL in the absence of diagnostic increases in serum creatinine, is able to detect some patients affected by subclinical AKI who have an increased risk of adverse outcomes. These results also suggest that the concept and definition of AKI might need to be reassessed.

Study published in Semin Nephrol. 2012 Jan;32(1):121-8., by Ronco, is more interesting. They made an attempt to couple the biomarkers NGAL and B-type natriuretic peptide (BNP) to define the diagnosis of both AHF and AKI in the early phases of Cardio-Renal syndrome (CRS) type 1.

B-type natriuretic peptide also known as Brain natriuretic peptide (BNP), and it is a 32 amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of heart muscle cells (cardiomyocytes). The main clinical utility of BNP is that:

– a normal level rules out heart failure (ref. 4)

– be used for screening and prognosis of heart failure (ref. 5)

– typically increased in patients with left ventricular dysfunction, with or without symptoms. BNP accurately reflects current ventricular status, as its half-life is 20 minutes (ref. 6)

– BNP can be elevated in renal failure. The natriuretic effect of BNP leads to an increase in urine production.

CRS is a common and complex clinical condition in which multiple causative factors are involved. It is a condition characterized by kidney failure and heart failure. The primarily failing organ may be either the heart or the kidney, and it is often this failing organ that precipitates failure of the other.

The Cardiorenal syndrome is divided by Ronco et al. into five subtypes (ref. 1,2,3):

Type 1
In type 1 (acute) CRS, acute decompensated heart failure leads to acute kidney injury.
Type 2
Type 2 (chronic) CRS is characterized by chronic heart failure that leads to chronic kidney disease.
Type 3
Also called the acute renocardiac syndrome, type 3 CRS is due to acute kidney injury that leads to acute cardiac dysfunction such as arrhythmia or heart failure.
Type 4
Type 4 CRS, or chronic renocardiac syndrome, is characterized by primary chronic kidney disease that contributes to cardiac dysfunction.
Type 5
Also called secondary CRS, the fifth type of CRS is combined heart and kidney dysfunction due to systemic disorders such as sepsis and systemic lupus erythematosis.

In type 1, as is the case in this article, the time window between renal insult and development of acute kidney injury (AKI) in acute heart failure (AHF) can be varied in different patients and AKI often is diagnosed too late, only when the effects of the insult become evident with a loss or decline of renal function. Thus the authors probably identified the need to coupling the biomarker NGAL with BNP to define the diagnosis of both AHF and AKI in the early phases of Cardio-Renal syndrome (CRS) type 1.

  1. ^ Ronco C, Haapio M, House AA, Anavekar N, Bellomo R (November 2008). “Cardiorenal syndrome”. J. Am. Coll. Cardiol. 52 (19): 1527–39. doi:10.1016/j.jacc.2008.07.051PMID 19007588.
  2. ^ Ronco C, Chionh CY, Haapio M, Anavekar NS, House A, Bellomo R (2009). “The cardiorenal syndrome”Blood Purification 27 (1): 114–26. doi:10.1159/000167018PMID 19169027.
  3. ^ Ronco C, McCullough P, Anker SD, et al. (December 2009). “Cardio-renal syndromes: report from the consensus conference of the Acute Dialysis Quality Initiative”Eur Heart J Epub ahead of printdoi:10.1093/eurheartj/ehp507PMID 20037146.
  4. ^ Maisel A, Krishnaswamy P, Nowak R, McCord J, Hollander J, Duc P, Omland T, Storrow A, Abraham W, Wu A, Clopton P, Steg P, Westheim A, Knudsen C, Perez A, Kazanegra R, Herrmann H, McCullough P (2002). “Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure”.N Engl J Med 347 (3): 161–7. doi:10.1056/NEJMoa020233.PMID 12124404.
  5. ^ Bhalla V, Willis S, Maisel AS (2004). “B-type natriuretic peptide: the level and the drug–partners in the diagnosis of congestive heart failure”. Congest Heart Fail 10 (1 Suppl 1): 3–27. doi:10.1111/j.1527-5299.2004.03310.x.PMID 14872150.
  6. ^ Atisha D, Bhalla MA, Morrison LK, Felicio L, Clopton P, Gardetto N, Kazanegra R, Chiu A, Maisel AS (September 2004). “A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction”. Am. Heart J. 148 (3): 518–23. doi:10.1016/j.ahj.2004.03.014.PMID 15389242.


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