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NGAL expression increased in several aseptic pathological conditions such as cancers, inflammatory
diseases and acute kidney injury, suggesting NGAL has other functions (Viau et al, 2010).
NGAL controls growth of renal tubules and cysts. It was also showed that inhibition of LCA2 gene,
caused inhibition of tubular cell proliferation which led marked decreased in cyst formation, which
suggest that Lcn2 might act as tubulogenic factor that controlled cell growth (Viau et al,2010). In
animal study on dogs with azotemia, plasma NGAL showed sensitivity 65% and 82% specificity. It
might be helpful to differentiate AKI from CKD (Steinbach et al, 2014).
NGAL has non renal function. It is upregulated in preeclampsia, Helicobacter pylori infections, β-
thalassemia, thyroid neoplastic cells, obstructive sleep apnoea syndrome, leptospirosis, various
cancers, HIV associated nephropathy, malaria included acute kidney injury, Atherosclerosis and
scrub typhus (Roudkenar et al, 2008; Iannetli et al, 2008; Peralta et al, 2012; Srisawat et al, 2015;
Voulgaris et al, 2019; Sun et al, 2017; Candido et al, 2014 ; Paragas et al, 2009 ; van Wolfswinkel et
al, 2016; Kim et al, 2013; ALpizar-Alpizar et al, 2009). In a mercury induced nephropathy study, NGAL
levels increased by 6.67% considering it as bio marker for mercury induced nephropatoxicity (Francis
et al, 2019).
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In an animal study by Shobha et al, showed that NGAL is better biomarker than urea and it may help
to detect early kidney injury. In this study NGAL was detected within 3 hours after contrast induced
nephropathy, whereas urea elevated after 12 hours (Shobha et al, 2016). In another animal study,
NGAL was detected at apical side of distal convoluted tubules in low and high doses on day 1 of
Gentamicin induced nephrotoxicity (Luo et al, 2016). In an another study on cats, NGAL monomer
and MMP-9 monomer significantly associated with elevated levels of convectional biomarkers linked
to renal disease (Wu et al, 2019). This proved monomeric form origination form tubular epithelial
cells. This shows specificity of NGAL to renal disease. NGAL has 3 different forms; 27 KDa monomer,
48 kDa homodimer and 140 KDa NGAL/MMP-9 complex forms. Monomer form of NGAL is
predominant in renal tubules, homodimer form released from neutrophils. Therefore, NGAL has
different functions (Guo et al, 2008). Increased NGAL protein is released into circulation, freely
filtered by glomerulus and reabsorbed in proximal tubules. Thus, on renal tubular damage, excretion
of NGAL is increased (Rhee et al, 2015).
In a multi centric observation cohort study, chronic renal insufficiency cohort (CRIC) study on 3939
CKD patients, urinary NGAL levels correlated with severity of CKD and is a predictive of CKD
progression. (Liu et al, 2013). In a prospective cohort study, serum and urinary NGAL levels were
measured in CKD. Both serum and urinary NGAL levels were inversely independently closely related
to eGFR. NGAL massively released into blood and urine from injured tubular cells. It was proved that
serum/urine NGAL had prognostic power for renal progression in CKD patients. Hence, represents as
surrogate marker of renal function (Balignano et al, 2009).