albuminuria ( i.e. , urinary albumin , or ua ) is defined as an abnormally high amount of albumin in the urine and is a strong sign of early renal damage [ 14 ] . in type 2 diabetes and nondiabetic subjects ,
albuminuria is also associated with early- and long - term cardiovascular mortality [ 5 , 6 ] .
elevated ua reflects a general state of widespread endothelial dysfunction and vascular damage [ 710 ] .
inflammation and endothelial dysfunction may be key mechanisms in the development of albuminuria [ 1113 ] .
however , evidence of an association between markers of inflammation and albuminuria is limited and controversial .
in diabetic subjects with albuminuria , no differences in c - reactive protein levels ( a marker of inflammation ) were observed compared with healthy controls . yet in another study , serum levels of sialic acid , another marker of inflammation , correlated with increasing albumin excretion
. absolute neutrophil count ( anc ) is also a sensitive marker of inflammation , and the test for it is simple and inexpensive .
recently , clinical studies have shown a link between neutrophils and the development of diabetic retinopathy [ 1618 ] .
although albuminuria is an accepted sign of early renal injury , it is not known whether the anc is related .
we hypothesized an association between anc and ua levels . like the world 's human population in general ,
china 's is aging and we chose to study the elderly . here , the ua creatinine ratio ( uacr ) was used as a measure of albumin excretion . since overnight
uacr correlates well with ua excretion , this study specifically investigated an association between systemic anc and uacr in an elderly chinese population .
this community - based , cross - sectional study focused on the clinical risk factors of albuminuria .
we performed the study with outpatients of our hospital in shanghai , from march to august of 2010 .
all community - dwelling participants aged 60 years , including those residing in private residences and personal care homes , were recruited to a platform of chronic disease ( pcd ) prevention program for a routine medical checkup .
participants who could not come to the prevention center were interviewed in their place of residence by trained personnel .
all questionnaires and procedures were approved by the institutional review board in our hospital for research with human subjects .
the identification of diabetes was based on the diagnostic criteria recommended by the american diabetes association in 1997 .
potential subjects included those with a history of past diabetes or who had newly received a diagnosis by oral glucose tolerance test . in total ,
3053 subjects aged between 60 and 91 years ( median age : 70  y ) were considered for the study .
the following subjects were excluded : 28 subjects presenting with painful urination , fever , cough , or skin damage ; 5 subjects who were incontinent and not capable of caring for themselves ; and 12 subjects with white blood cell ( wbc ) counts 10  10/l or serum creatinine ( scr ) 141 
further 738 subjects had missing ua data , because they did not collect morning urine samples . therefore
the subjects underwent a glucose tolerance test with a 75  g oral glucose overload .
the blood samples were collected by edta tube before and at 2  h after the tolerance test .
glucose , cholesterol , triglycerides , scr , and alanine aminotransferase ( alt ) levels were measured using a dimension vista analyzer ( siemens ag ) .
wbc , anc , and anc / wbc ratio values were measured using an automated 5-category hematology analyzer ( japanese sysmex xs1000i ) .
participants were asked to collect a random morning spot urine sample in a clean , lidded container .
all urine samples were assessed centrally in a single reference laboratory at fifth hospital , shanghai , china .
samples were centrifuged at 1500  g for 10  min and then stored at 80c prior to analysis .
test results were considered positive for albuminuria ( ua ) at an albumin - to - creatinine ratio ( acr ) > 0  mg / g ; otherwise the results were accepted as negative ( ua ; acr = 0  mg / g ) .
microalbuminuria , or a moderate increase in ua , was identified as an acr from 30 to 299  mg / g .
blood pressure was measured twice at about 8:00 a.m. , with the subject seated and with an interval of 5  min between measurements .
blood pressure measurements were taken on the right arm , which was relaxed and supported by a table , at an angle of 45 from the trunk ( sphygmomanometer , yutu , shanghai , china ) .
hypertension was defined as systolic blood pressure ( sbp ) 140  mmhg or diastolic blood pressure ( dbp ) 90  mmhg .
the following measurements were recorded for all subjects : height , weight , waist circumference ( horizontal position of the anterior superior iliac crest and twelfth rib edge midpoint ) , and hip measurement ( measuring horizontally from the front of the pubic symphysis to the most convex point behind the gluteus maximus ) by experienced nurses in the pcd program . body mass index ( bmi ) was calculated as weight / height ( kg / m ) .
mann - whitney u tests and chi - squared tests were used for analysis of continuous variables and categorical variables , respectively .
the anc levels of the following subgroups of patients were calculated and compared by analysis of variance : nondiabetic ; diabetic without albuminuria ; diabetic with low - level albuminuria ( 0 < ua < 30  mg / g ) ; diabetic with microalbuminuria ( ua 30299 
mg / g ) ; and diabetic with macroalbuminuria ( ua  300  mg / g ) .
all subjects were categorized into 5 groups according to the quintile of anc levels ( i  v ) .
multivariate logistic regression analysis was used to investigate an independent association between anc and ua .
areas under the roc ( auc ) curve 0.5 were considered statistically significant ( spss software version 17.0 ; spss , chicago , il , usa ) .
the data analysis included 2265 participants aged between 60 and 91 years ( median : 70  y ) with a male - to - female ratio of 56.8 to 43.1 ( table 1 ) . compared with the 1011 participants who were free of diabetes , the 1254 participants with diabetes were older , with a higher prevalence of hypertension and increased sbp , anc , wbc , anc / wbc , and fasting blood glucose ( fbg ) .
the 641 participants testing positive for uacr ( ua ) were older , with higher bmi and waist - to - hip ratio , sbp , dbp , scr , anc , wbc , and anc / wbc compared with the 1624 persons testing negative for uacr ( ua ) .
as described in subjects and methods , all subjects were classified as follows : nondiabetic ; diabetic without albuminuria ; diabetic with low - level albuminuria ; diabetic with microalbuminuria ; or diabetic with macroalbuminuria ( figure 1 ) . anc levels and anc / wbc increased with the severity of ua ( p < 0.0001 ) .
patients with macroalbuminuria had significantly higher anc and anc / wbc counts than did the patients in the other 4 groups ( p < 0.001 )
regarding the results of the multivariate logistic regression analyses , after adjustments for age , bmi , gender , sbp , dbp , and scr , the odds ratios ( ors ) indicated that anc levels significantly correlated with risk of macroalbuminuria ( p < 0.0001 ) . compared with quintile i of anc , quintile v of anc had the highest or value ( 2.311 , 95% confidence interval [ ci ] : 1.6083.321 ; table 2 ) .
roc curves were plotted to evaluate the diagnostic value of age , bmi , waist - to - hip ratio , gender , sbp , dbp , alt , scr , total cholesterol , triglycerides , fbg , 2-hour glucose , and anc for macroalbuminuria .
anc was the strongest predictive factor for macroalbuminuria ( auc = 0.6001 ) followed closely by fbg ( auc = 0.5876 ) and sbp ( auc = 0.5767 ; table 3 ) . to investigate interactions among anc , fbg , sbp , and scr ,
fbg  sbp ( model 2 ; variables are multiplied ) and anc  fbg  sbp  scr ( model 3 ) indicated 1.67% and 3.12% increase , respectively , in the predictive value for macroalbuminuria , compared with model 1 ( anc  fbg ) , but these increases were not statistically significant ( p = 0.5188 and 0.5338 ) . thus anc and fbg were the most meaningful diagnostic indices for macroalbuminuria .
we found that ancs significantly increased in diabetes with macroalbuminuria , and anc was the strongest factor predicting macroalbuminuria .
these results indicate that neutrophil - mediated inflammation may be involved in the exacerbation of albuminuria . to the best of our knowledge ,
this is the first report describing an association between ua and anc levels in a population - based study .
it is perplexing that the systemic neutrophil count , a very simple and inexpensive laboratory parameter , has not been reported previously in association with ua , although data from a study of 30  793 people conducted in korea showed an association between anc and diabetic retinopathy , after adjusting for the effects of blood pressure , blood glucose , and scr . in our present study ,
patients with albuminuria or those with diabetes had higher anc levels . to study further the association between diabetes , ua , and anc
, subjects were stratified into a nondiabetic group and 4 groups with diabetes at different levels of severity of albuminuria .
we found that patients with diabetes with macroalbuminuria had a notably higher mean anc than did the other 4 groups .
in addition , anc was an independent indicator of macroalbuminuria , but it was not an independent indicator of ua .
thus , anc might have an important role in accelerating the progression of albuminuria but not the formation of urinary protein .
although establishing a causal mechanism for the association between anc and albuminuria was beyond the scope of this study , the underlying link may concern vascular damage . in clinical and laboratory studies ,
elevated neutrophil counts were found associated with increased levels of tumor necrosis factor- ( tnf- )  , cytokine - induced neutrophil chemotactic factor 2 alpha / beta ( cinc-2/ ) , interleukin- ( il- ) 1 , il-6 , and c - reactive protein , as well as excessive production of superoxide and reactive oxygen species [ 2023 ] . based on the results of the present study and past investigations , we hypothesize that the systemic neutrophil count reflects the local number of neutrophils in renal vessels [ 24 , 25 ] . under the influence of proinflammatory cytokines , neutrophils in renal vessels are activated and their adhesion is intensified . these responses cause abnormal leukocyte - endothelial interactions and ultimately vascular damage . in the present study , compared with the other 4 quintile anc groups , the highest level of the anc group had the highest or for the risk of macroalbuminuria and not quintiles ii or iii .
this shows that the higher the anc level , the more likely the presence of macroalbuminuria , reflecting an overtly inflammatory status in patients with macroalbuminuria [ 24 , 27 ] .
the exact mechanism is not clear , but whether changes in the function or shape of neutrophils are involved warrants further research .
first , the study design was cross - sectional and therefore we were not able to confirm a causal link between anc and macroalbuminuria .
second , the inclusion of participants attending a routine health checkup in one community represents a potential source of selection bias , which should be considered when interpreting the results .
third , information regarding other traditional risk factors for albuminuria , such as heavy exercise , could not be obtained and analyzed in this study . despite these limitations
, our study involved many clinical and laboratory parameters in a large number of subjects and showed a new clinical risk factor for albuminuria in individuals , 60 years of age and older .
the potential effect of neutrophil - mediated inflammation in the progression of macroalbuminuria warrants further research .
 
 background . this study investigated an association between systemic absolute neutrophil count ( anc ) and albuminuria in elderly chinese people . 
 methods . 
 a cross - sectional study was conducted on 2265 participants attending a routine medical examination in minhang district as part of a platform of chronic disease program . their drug history , waist circumference , height , blood pressure , 
 fasting blood glucose , anc , and urine albumin levels were recorded . 
 this study conformed to the requirements of the strobe statement . 
 results . of the 2265 subjects , 1254 ( 55.4% ) were diabetic and 641 ( 28.3% ) had albuminuria . 
 the mean anc of patients with diabetes comorbid with macroalbuminuria was significantly higher than that of both the nondiabetic patients and patients with diabetes with lower levels of albuminuria ; the latter 2 groups had statistically similar anc . 
 anc significantly and positively correlated with levels of urine albumin . based on multivariate analysis , with each 109/l increase in anc , 
 the increase in rates of macroalbuminuria was significant but not in rates of albuminuria positivity . 
 based on areas under the receiver operating characteristic curve , anc was the strongest factor predicting macroalbuminuria . 
 conclusions . 
 elevated anc was associated with macroalbuminuria in diabetes , indicating that neutrophil - mediated inflammation may be involved in the exacerbation of albuminuria . 
1. Introduction
2. Subjects and Methods
3. Results
4. Discussion
5. Conclusion