Early Warning Significance Of The Low Molecular Weight Protein Urine Joint Detecting In Renal Damage Of Neonatal Meconium Stained Amniotic Fluid

[Background]Meconium-stained amniotic fluid (MSAF) is one of the clinical manifestations of fetal distress, mean fetal hypoxia. When fetal intrauterine hypoxia appears, in order to ensure the blood supply of the vital organs such as the heart and brain, and mesenteric vascular contraction increased intestinal peristalsis frequency increases, the anal sphincter relaxation, will make a lot of meconium into the amniotic fluid, MSAF appears. Falciglia HS reported [1]in the birth of all live births, the incidence of MSAF appears approximately7%-20.4%, of which about2%to9%[2]neonatal meconim aspiration syndrome (MAS), the mortality rate of the latter can be up to5%to40%[2]. In addition, MSAF may also cause neonatal hypoxic-ischemic encephalopathy (HIE), asphyxia, even death, and Ojha RK found that HIE about50%had MSAF at birth. So judging MSAF in fetal distress diagnostic value is very necessary. Linxi [4]reported that gestational age less than37weeks of neonatal MSAF rate was about2.67%, and full-term children about17.37%,expired births approximately85.28%. However, there are also studies [5,6]that the presence of MSAF at birth, the fetal heart rate is normal, the children may be associated with a very good prognosis. Academic studies [5,6]show that the degree and time of MSAF, and fetal perinatal disease early labor MSAF, fetal heart rate abnormalities and neonatal asphyxia incidence increased significantly, and the late labor MSAF, fetal heart rate abnormalities and neonatal asphyxia incidence decreased significantly. At present, the majority of studies suggest that the increased incidence of fetal perinatal diseases and MSAF[7-8].Neonatal asphyxia is often a continuation of fetal distress, fetal distress is often the major cause of death of neonatal asphyxia and perinatal newborn. Neonatal asphyxia easily lead to hypoxemia and acidosis, the most common emergencies after the birth,it must be actively rescued and the proper treatment, to reduce the incidence and mortality of the disease of the newborn, and the prevention of the occurrence of the long-term sequelae. The essence of the neonatal asphyxia kidney damage is hypoxic-ischemic renal injury, the reasons to the high incidence of kidney damage is the result of fetal intrauterine hypoxia adaptive response, such a response by the renin-angiotensin-aldosterone system the role of the in vivo blood flow redistribution to maintain the blood supply of the vital organs such as the heart, brain, adrenal, kidney, intestine, and a significant reduction in skin blood supply. In recent years, the study of hypoxic-ischemic kidney damage gradually increased, as a study of a new hot spot.All as we known, tubular as an important part of the nephron, about95%, more than the total capacity of the glomerulus, compared with glomerular has high vulnerability, which hypoxic-ischemic is the most common cause renal damage one of the three major reasons. Pediatric renal unit development is a gradual process[9], the neonatal period has yet to develop improved almost100%hypoxic newborns, can cause renal tubular function by a series of pathological changes in this physiological basis of concurrent hypoxia-induced damage.Neonatal period renal dysfunctions are often atypical symptoms or complications are more difficult to identify. In recent years, with the development of perinatal medicine and renal function tests means improved neonatal renal damage reported incidence increased significantly. Some studies have shown that newborns with acute kidney damage have the risk of the development of chronic kidney disease and hypertension[10].Therefore, neonatal renal dysfunction to achieve early diagnosis and aggressive treatment of kidney damage is necessary to reduce perinatal mortality and achieve important prenatal and postnatal care.At present, organ damage in neonatal asphyxia incidence may be as high as82%, approximately41.57%[11-12] of kidney damage while China reported the neonatal asphyxia organ injury incidence rate of74.8%, approximately52.9%of renal injury. Neonatal asphyxia can lead to kidney damage in children with oliguria or anuria, hence resulting in the water, electrolyte and acid-base balance disorders, severe cases can cause acute renal failure and life-threatening, so finding a way to reflect early renal sensitive indicator of damage, reasonable guide clinical treatment to improve the prognosis of many scholars at home and abroad are quite concerned research direction. There are a number of renal early damage detection indicators, mostly based on the change of GFR and renal tubular reabsorption. Creatinine clearance rate (CCr) is clinically recognized more accurately reflect the GFR change[13], but due to the the CCr need specimens from24h urine and pumping blood twice detection operation is complicated and can not be due to disease progression, conducted repeatedly determination. Addition extrapolated by the three variables of gender, age, plasma Cr difficult to calculate accurately, and vulnerable to a variety of factors, the results unsatisfactory accuracy and sensitivity. So it need high sensitivity detection indicators in this clinical specificity.For a long time, clinical general oliguria, azotemia and creatinine as diagnostic indicators, as the major judgment glomerular filtration rate (GFR) and the primary hospital diagnosis of neonatal renal most basic and commonly used experimental project is detection serum BUN, Cr. Oliguria symptoms in a newborn can easily be ignored, but BUN, Cr merely moderately sensitive. Some scholars believe that, although BUN as the evaluation of renal function, but it can not meet the requirements of the endogenous marker of glomerular filtration rate, and the influence of body disease status, such as congestive heart failure, malnutrition, eating difficulties etc.; the more important it is the tubular passive reabsorption. Cr as renal evaluation indicators for over40years, its detection is simple and low-cost. However, studies have shown that Cr levels by age, gender, body shape, height, muscle mass and dietary structure factors. Therefore, Cr is not reliable. According to the study of BUN, Cr as GFR judged by neonatal assessment and prognostic indicators biggest drawback is poor sensitivity, especially in the early stage of acute renal dysfunction, BUN and Cr are not necessarily abnormal, compensatory ability of neonatal kidney, and atypical clinical manifestations of early renal damage, show that60%to70%effective renal units are destroyed when BUN, Scr higher than normal, the condition has worsened, such as inadequate attention, the condition may develop further. More than50%reduction in GFR[15], Cr and BUN have obviously reflect, no reflection of the GFR, can not be used as indicators of early renal dysfunction. Not sensitive enough to show that the traditional method of detection of renal easily missed lesions early or mild acute renal dysfunction in children. So clinical need safer, more convenient, more specificity, and high sensitivity to find the early renal damage.Renal pathology is directly based on the most reliable diagnosis of kidney disease, renal biopsy has become a routine examination of the Department of Nephrology, but as traumatic, difficult operation, with a certain risk, renal biopsy can not be used as routine, dynamic testing means popularity at the grassroots level hospitals. Yamaguchi Y[16]found that renal tubular damage suffered in the process of renal injury after neonatal asphyxia may be earlier than the glomerulus, the proximal tubular epithelial cells particularly sensitive to hypoxia, choose a way to early ideal indicators for the diagnosis of renal tubular damage, early diagnosis, early treatment is of great significance for hypoxic-ischemic kidney damage.Estimates of trace amount of protein in the urine of patients with kidney disease in recent years have been more and more attention [17,18]. The importance of tubulointerstitial injury has been more and more attention of Chinese and foreign scholars. Determination of trace protein in the urine Series to become the primary means of detection of glomerular and tubular function in recent years[19,20],mainly including IgG, TRF, Alb, NAG, α1-MG, β2-MG, RBP, etc., in which the first three are mainly reflect kidney the ball, after four reflect renal tubular damage. Detected in trace amounts in urine microalbumin (mALB) not only can accurately reflect the situation of renal injury, also was a simple operation, no damage, easy to automate[21]. The urine mALB was recognized secondary nephropathy early diagnosis of highly sensitive and highly specific indicators[22]. α1-MG is a glycoprotein with a molecular weight of26,100, its free state or in combination with the high molecular proteins exist in the blood, the free state of α1-MG by glomerular filtration, and most of the kidney proximal convoluted tubule reabsorption, and a small amount from the urine, increased its displacement when impaired renal proximal tubule, so α1-MG sensitive reflects tubular function, β2-MG is widely present in the blood, urine and other body fluids.The normal blood level was very stable2mg/L, almost all from the glomerular filtration, and99%of the proximal convoluted tubule reabsorption and intracellular lysosomal system decomposition. β2-MG as classic tubular marker protein, can be a direct reflection of renal tubular function. Wu Hongmer[23] reported kidney damage in children check urine and urinary protein, it may appear normal, and the urine trace protein increased the children for the renal biopsy, kidney damage significantly. Therefore, you can not qualitative or urinary protein excretion of urinary protein as early indicators of kidney injury, and urinary microalbumin indicators than urine routine urine protein qualitative and serum renal function tests occur earlier and higher sensitivity. Urine trace protein, can be as soon as possible to reflect the renal injury, can guide clinical treatment. This check sampling is convenient, non-invasive, and is particularly suitable for newborns. Through the dynamic changes of the urine trace protein test can make us more sensitive to early evaluation of kidney function. Most hospitals have conditions to detect trace protein in urine, and specimen collection is convenient, simple operation, reliable test results and avoid iatrogenic anemia caused due to repeated blood, can be used as a monitoring and early neonatal kidney damage conventional effective method worthy of promotion.In summary, we can see MASF can cause neonatal multiple organ damage, but whether the merger neonatal renal dysfunction, fewer reports. UrineP2-microglobulin (β2-MG), urinaryα1-microglobulin (ai-MG) and urinary microalbumin urine (mALB) and other low molecular weight protein with meconium staining of renal damage may be relevant, But the research associated with kidney damage mainly in its relationship with the level of serum BUN, Cr, a guide clinicians meconium staining caused kidney damage early diagnosis is of limited value. Therefore, this study by measuring neonatal blood gas analysis, BUN, Cr, β2-MG, α1-MG and mALB, explore neonatal low molecular weight protein in meconium staining kidney damage to the significance of early diagnosis. To provide experimental evidence for clinicians timely and accurate processing meconium staining caused kidney damage.[Objective]Detecting neonatal urine in the urinary beta2-microglobulin (β2-MG), urinaryα1-micro-globulin (α1-MG) and urinary albumin (mALB) the urine low molecular weight protein levels, to investigate explore the clinical significance of combined detection of urinary low molecular weight protein in neonatal meconium staining of renal damage.[Method]1. Grouping methodA case-control study of the method, select120cases of full-term newborns born in Zhongshan City People’s Hospital from March2012to September2012, including90cases of meconium-stained amniotic fluid for the study group, divided according to the degree of meconium staining degree Ⅰ degree Ⅱ, Ⅲ degree; clear amniotic fluid of normal newborns and30cases in the control group, and determination of neonatal blood gas analysis, blood urea nitrogen (BUN), creatinine (Cr), urinary β2-microglobulin (β2-MG), urinary α1-microglobulin (α1-MG) and urinary albumin (mALB) content.2. Statistical methodsEstablish a database using the SPSS17.0statistical package. Between the two groups using t test, analysis of variance was used to compare the groups, unequal variances, the Welch method, pairwise comparisons using LSD method. When variances are unequal. a=0.05as the inspection level, P<0.05show it is statically significant. [Results]1.Sex, age, body weight, etc. Usually ComparisonTerm meconium stained newborns90cases, including48males and42females,37to42weeks gestational age at birth (average39.50±0.95weeks), weighing2500～4000g (average3571.11±438.30g), which amniotic fluid I degree of meconium-stained32cases, Ⅱ degree meconium-stained30cases,28cases of Ⅲ degree of meconium contamination, unused diuretics nephrotoxic drugs. Select the other30cases the hospital obstetric born normal newborn, including16males and14females, born37to42weeks of gestational age (average39.42±1.26weeks), weight of2500～4000g (average3477.59±510.69g) control group. Stained amniotic fluid in children with normal neonatal gender, gestational age, birth weight was no significant difference (P>0.05), comparable.2.Meconium-stained amniotic fluid Ⅲ degree of serum urea nitrogen (BUN), creatinine (Cr), urinaryβ2-microglobulin (β2-MG), urinaryα1-microglobulin (α1-MG) and urinary microalbumin (mALB highest) level, meconium-stained amniotic fluid II degree group, followed by meconium-stained amniotic fluid grade I group the lowest. Amniotic fluid Ⅰ, Ⅱ degree Ⅲ degree of meconium-stained cord blood blood gas analysis of PH values were7.25±0.34,7.22±0.32,7.16±0.23, cord blood PH value decreased with increasing degree of meconium staining and III degree of fecal the transfected group average is less than7.20, neonatal acidosis.3.Amniotic fluid Ⅰ, Ⅱ, Ⅲ degree of meconium-stained group indicators were compared with normal control group, serum urea nitrogen and creatinine levels in amniotic fluid Ⅰ, Ⅱ degree Ⅲ degree of meconium-stained group compared with control group, there was no significant difference in statistics significance (P>0.05). Urine β2-microglobulin, urinary α1-microglobulin and urinary microalbumin levels of Ⅰ and Ⅱ degree of meconium staining group and the normal control group, the difference was not statistically significant (P>0.05). Urinaryβ2-microglobulin, urinaryα1-micro-globulin and urinary microalbumin level in meconium-stained amniotic fluid Ⅲ degree and control groups compare, the difference was statistically significant (P<0.05). Amniotic fluid Ⅰ,Ⅱ degree of meconium-stained group, umbilical cord blood pH values were within the normal range, respectively, compared with the control group, the differences were not statistically significant (P>0.05). Meconium-stained amniotic fluid III degree group, umbilical cord blood pH value of7.25±0.34, compared with the control group, the difference was statistically significant (P<0.05).[Conclusions]The combined detection of Low molecular weight protein urine meconium staining of renal damage caused by early discovery and evaluation of amniotic fluid is of certain significance to the extent.