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

Glassford, NJ 1 Schneider, AG 1 Eastwood, G 1 Peck, L 1 Young, H 1 Bellomo, R 1

[1 ] Department of Intensive Care, Austin Hospital, Heidelberg, VIC, Australia

Introduction

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].

Methods

To test this hypothesis, we studied ICU patients developing SIRS and oliguria or a 25 μmol/l increase in serum creatinine within 48 hours of ICU admission. We sought to determine if a relationship existed between FENa and NGAL in patients, with and without sepsis, developing AKI. We measured the serum and urinary NGAL, creatinine and sodium of patients with SIRS and either oliguria or an increase in creatinine within 48 hours of admission to a tertiary referral ICU. Point-of-care creatinine measurements were used to identify the maximum RIFLE category of AKI developed within the first 5 days of admission. The strength of the relationship between variables was determined using Spearman's rank correlation coefficient.

Results

We enrolled 93 patients between 31 August 2010 and 17 November 2010; 17 had an APACHE III diagnosis of sepsis. Serum NGAL and urinary NGAL when corrected for urinary creatinine were found to correlate moderately well with FENa in patients without sepsis, a relationship that weakens with the progression of AKI in this group. No other correlation showed a significant relationship (Table 1).

Table 1

Relationships between NGAL, FENa and AKI

Urinary NGAL Urinary NGAL corrected for urinary creatinine Serum NGAL Urine:serum NGAL ratio




FENa n Spearman P value Spearman P value Spearman P value Spearman P value
Nonseptic No AKI 43 0.153 0.328 0.587 <0.0001 0.450 0.002 -0.009 0.953
AKI 33 -0.039 0.830 0.438 0.011 0.258 0.148 -0.235 0.188
RIFLE R-F 14 0.015 0.958 0.235 0.418 -0.077 0.793 -0.068 0.817
Septic No AKI 12 -0.168 0.602 -0.007 0.983 0.232 0.467 -0.427 0.167
RIFLE R-F 5 -0.300 0.624 0.500 0.391 0.112 0.858 -0.400 0.505

Conclusion

The lack of a strong correlation FENa and NGAL in patients developing RIFLE I and F AKI suggests that changes in NGAL and changes in sodium resorption occur as a consequence of different stimuli in the pathogenesis of the syndrome. The absence of any observed relationship between NGAL and FENa in septic patients suggests a pathological process different from that underlying nonseptic AKI. The small sample size may be a confounding factor.

1  

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2  

Siew ED, Ware LB, Ikizler TABiological markers of acute kidney injuryJ Am Soc Nephrol(2011) 22: 810820 10.1681/ASN.2010080796 Pubmed ID: 21493774

3  

Cruz DN, de Cal M, Garzotto F, Perazella MA, Lentini P, Corradi V, Piccinni P, Ronco CPlasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU populationIntensive Care Med(2010) 36: 444451 10.1007/s00134-009-1711-1 Pubmed ID: 19956925

4  

Kanbay M, Kasapoglu B, Perazella MAAcute tubular necrosis and pre-renal acute kidney injury: utility of urine microscopy in their evaluation - a systematic reviewInt Urol Nephrol(2010) 42: 425433 10.1007/s11255-009-9673-3 Pubmed ID: 19921458

5  

Ishikawa K, May CN, Gobe G, Langenberg C, Bellomo RPathophysiology of septic acute kidney injury: a different view of tubular injuryContrib Nephrol(2010) 165: 1827 Pubmed ID: 20427951