the perioperative period of major oncological surgery is marked by several potential causes for renal injury such as hypotension , volume depletion , self - regulation disorders of the kidney , surgical trauma and drug - induced nephrotoxicity .
on the other hand , patients with oncological malignancies are susceptible to various kidney insults that are associated to complications from the disease itself or from its treatment , such as chemotherapy and radiotherapy .
thus , surgical stress would potentiate various risk factors to kidney injury previously present in the carriers of malignancies , resulting in increased length of hospitalization , infectious complications , and mortality rates . in the last few years
, several researchers have been trying to find serum and urinary biomarkers that could detect earlier or even predict the evolution to acute kidney injury ( aki)/failure in patients at risk .
neutrophil gelatinase - associated lipocalin ( n - gal ) is a widely studied early biomarker of ischemia and kidney injury , which allows the identification of patients at a higher risk of kidney injury 48 h before traditional detection methods , thereby allowing the implementation of preventive / protective strategies before renal damage becomes irreversible . considering the negative impact of aki among oncology patients , this study intended to assess the efficacy of urinary n - gal as an early biomarker of aki immediately after major oncological surgeries in patients admitted to the intensive care unit ( icu ) .
this was a prospective cohort study on consecutive patients diagnosed with solid neoplasia , submitted to elective or emergency surgeries , and admitted in the icu of a cancer hospital .
all adult patients ( aged > 18 years ) submitted to major oncological surgeries ( abdominal , pelvic , thoracic , or head / neck ) were included , since they previously had a normal renal function .
the exclusion criteria were : patients with a previous diagnosis of kidney injury or failure ( with or without renal replacement therapy ) , pregnant women , and terminal patients under exclusive palliative support .
acute kidney injury diagnosis was defined in accordance with the aki network definition of injury criteria .
selected variable data ( age , acute physiology and chronic health evaluation ii [ apache ii ] , n - gal , c - reactive protein - immediate postoperative [ crp - ipo ] , serum creatinine - ipo , serum creatinine 1 po , serum urea - immediate po and 1 po , length of hospitalization , operation time , and serum lactate - ipo ) were standardized using z function and later analyzed by principal component analysis ( pca ) , after verification of the data quality using kaiser - meyer - olkin ( kmo ) test .
it was possible to determine the explanatory variables for each of the patients , with a priori - defined outcome ( 0-normal ; aki ) .
urinary n - gal was measured at the time of admission in the icu using quantitative architect abbott ( chemiluminescent microparticle immunoassay ) method .
most of the patients ( 77% ) were males , with a mean age of 52.8 years .
patients with elevated urinary n - gal had higher apache ii score at admission , with a trend toward higher mean age compared with those with reduced n - gal .
there were no differences in gender , site of cancer , or related diseases [ table 1 ] .
demographic characteristics and clinical outcome of the patients according to urinary n - gal levels overall incidence of po aki was 13.6% .
patients with lower levels of urinary n - gal had lower incidence of aki ( lower levels of serum urea and creatinine ) and shorter length of hospitalization in the icu . when patients with or without the development of aki were compared , the urinary n - gal levels were found to be a strong outcome predictor of aki incidence [ table 2 ] .
the occurrence of aki increased the length of hospitalization in the icu , although it did not increase the mortality rate .
univariate analysis of the risk factors and outcomes among patients with or without the development of aki when the kmo test value was > 0.5 ( kmo = 0.695 ) , it was possible to verify that the variables post oncological surgeries were in accordance with the pca application assumptions , after removing the variables creatinine 1 po , urea 1 po , length of hospitalization , duration of surgery , and lactate - ipo .
correlation between matrix of variables was assessed using bartlett spherical test ( c = 53.097 , p < 0.0001 ) . using canonical analysis ( axes f1 and f2 )
, it was confirmed that age , n - gal , and apache ii score were the primary variables associated with aki outcome [ figure 1 ] .
when the kmo test value was > 0.5 ( kmo = 0.695 ) , it was possible to verify that the variables post oncological surgeries were in accordance with the pca application assumptions , after removing the variables creatinine 1 po , urea 1 po , length of hospitalization , duration of surgery , and lactate - ipo .
correlation between matrix of variables was assessed using bartlett spherical test ( c = 53.097 , p < 0.0001 ) . using canonical analysis ( axes f1 and f2 )
, it was confirmed that age , n - gal , and apache ii score were the primary variables associated with aki outcome [ figure 1 ] .
when the kmo test value was > 0.5 ( kmo = 0.695 ) , it was possible to verify that the variables post oncological surgeries were in accordance with the pca application assumptions , after removing the variables creatinine 1 po , urea 1 po , length of hospitalization , duration of surgery , and lactate - ipo .
correlation between matrix of variables was assessed using bartlett spherical test ( c = 53.097 , p < 0.0001 ) . using canonical analysis ( axes f1 and f2 )
, it was confirmed that age , n - gal , and apache ii score were the primary variables associated with aki outcome [ figure 1 ] .
this study showed that in the context of oncological surgery , the urinary n - gal level assessed at admission to the icu was a strong predictor of aki , and patients with higher values of n - gal showed a trend toward higher hospital mortality .
neutrophil gelatinase - associated lipocalin , as well as other lipocalins , is expressed biologically in various tissues , such as lungs , spleen , kidney , liver , brain , heart , and testicles , under healthy conditions in humans .
but under stress conditions , it is produced by neutrophils and performs complementary functions , by transporting inflammatory substances ( such as prostaglandins and arachidonic acid ) and mediating the action of iron during inflammatory process .
therefore , n - gal has possible immunological action during severe acute situations , such as sepsis and trauma . on the other hand , specifically in the kidney tissue ,
n - gal is upregulated in injuries ( particularly ischemic and by the use of contrast ) .
therefore , it is possible to say that plasma n - gal acts like a neutrophil activation biomarker and urinary n - gal acts like a tubular injury marker .
however , because of its small size and resistance to degradation , n - gal is easily detected in the blood and urine .
therefore , increased urinary n - gal detection could be affected by a kidney process ( aki ) or it might reflect a severe acute systemic inflammatory process ( e.g. , sepsis or trauma ) . during differentiation of various human tissues , n - gal may play a role in the genesis and , probably , the growth , proliferation , and diffusion of human neoplasms .
major surgeries can themselves result in severe systemic inflammatory process , which intrinsically would lead to higher mortality .
n - gal has been shown to be increased during the po period of major cardiac and noncardiac surgeries , correlating with the severity of inflammatory process and mortality , and even in other chronic and acute inflammatory conditions , such as extracorporeal circulation and inflammatory bowel disease .
acute kidney injury is common in the po period of major surgeries , with a strong impact on morbi - mortality , particularly in patients with cancer . despite its multifactorial nature ,
a characteristic feature of aki related to po period is its association with systemic inflammation processes . in the present study ,
urinary n - gal showed a strong correlation to kidney dysfunction and a tendency toward increase in mortality ( possibly not significant due to an insufficient number of patients ) . in this study , urinary n - gal , besides being clearly an aki predictor , was increased ( although without statistical significance ) in patients who died .
n - gal has been associated with unfavorable outcome in critical patients , particularly ( but not exclusively ) in sepsis and systemic inflammatory reaction syndrome ( sirs ) patients .
inflammation has an important role in cellular biology and cancer pathophysiology , either in the development and emergence of oncogenic mutations and metastasis formation or host reaction and eventual secondary immunosuppression .
moreover , secondary to major surgeries , particularly in patients with cancer , a systemic inflammatory process is triggered , including an immunosuppressive anti - inflammatory response - an activity that could be mediated by n - gal . in the current study ,
all patients were submitted to moderate to high - risk surgery , with severe po inflammation , as shown by the elevated crp levels . in the current study , age >
this could only be associated with the intrinsic higher severity of disease in these patients , with higher number of comorbidities and higher aki risk . however , although the literature is not clear regarding the correlation between age and n - gal levels , elderly patients with sirs / sepsis present greater inflammatory activity ( determined by biomarkers ) than younger patients .
hence , n - gal could hypothetically be a biomarker of age - related inflammatory activity in these patients .
the incidence rate of aki ( 13.6% ) and need for renal replacement therapy ( 4.5% ) in this study were compatible with literature .
aki incidence varying from 6.8% ( lung cancer ) and 17.3% ( pancreatectomy ) to 38.3% ( esophageal cancer ) has been described in hospitalized oncology patients , with a strong correlation to hospital mortality . in this study
, there was a small increase of aki incidence in gastrointestinal surgeries , although without statistical difference .
the main predictors of aki were older age , apache ii score , urinary n - gal , and crp , and the first three parameters maintained their predictability when subjected to multivariate analysis . in po patients , it has been shown that aki is correlated with disease severity , previous diseases ( such as chronic heart failure [ chf ] and diabetes ) , and abdominal surgery .
the crp level in critically ill sepsis cancer patients shows a strong correlation with the course of acute disease , thereby being a good marker of inflammatory process .
this study has some limitations , primarily because of a single center design and limited number of subjects .
in addition , n - gal serum level was not measured , which could better differentiate between systemic inflammatory process and kidney injury .
it has also been shown that urinary n - gal has a strong correlation with mortality and inflammatory process , independent of the presence of aki .
the serial measurement of n - gal was not performed , which could increase the predictability of the diagnostic test .
in addition , because two variables were studied ( oncological and at po status ) it would be difficult to arrive at conclusions on the relative impact of each one of the parameters involved in the development of aki .
in a small cohort of cancer patients submitted to major surgery and admitted to the icu , initial urinary n - gal was a predictor of po aki . patients with elevated urinary n - gal also showed a trend toward higher hospital mortality .
 background and aims : neutrophil gelatinase - associated lipocalin ( n - gal ) is an early biomarker of acute kidney injury ( aki ) due to various etiologies . on the other hand , n - gal 
 is also elevated in patients with acute inflammatory conditions and in several solid neoplasms . 
 the goal of this study was to assess the efficacy of n - gal as a predictor of aki and mortality in oncological surgical patients postoperatively in the intensive care unit ( icu).methods : this was a prospective cohort observation study on adult cancer patients submitted to elective or emergency surgeries and admitted in the icu . 
 urinary n - gal was measured at the first 2 h after admission . 
 aki incidence and other complications were assessed , including hospital mortality.results:a total of 22 patients were assessed ( 77% male , age 52.8 years , acute physiology and chronic health evaluation ii [ apache ii ] 17.3 ) in whom the most frequent site of cancer was the gastrointestinal tract . 
 aki incidence was 13.6% . 
 urinary n - gal was a predictor of aki ( 22.0 ng / ml in patients without aki vs. 239.1 ng / ml in patients with aki , p < 0.001 ) . 
 multivariate analysis showed that the main predictors of aki were age , apache ii , and n - gal . 
 n - gal was also higher , although not statistically significant in patients who died in the hospital.conclusions:in oncological postoperative patients admitted to the icu , urinary n - gal was an independent predictor of aki ; moreover , its level was higher in the deceased patients . 