Diagnostic And Predictive Value Of Random Spot Albuminuria To Creatinine Ratio In Women With Hypertensive Disorders Complicating Pregnancy

Hypertensive disorder complicating pregnancy (HDCP) is a common and specific pregnancy-associated systemic disease, which is characterized by new onset of hypertension and proteinuria after 20 weeks of gestation. Preeclampsia is a serious type of HDCP accompanied by multiple organ damage, and the severe cases can appear HEELP syndrome, placental abruption, cerebral hemorrhage, pulmonary edema, twitch, coma, heart and renal failure, disseminated intravascular coagulation (DIC), fetal growth restriction (FGR) etc, even maternal infant to die with the maternal mortality rates of 4.2/100000. Epidemiological investigations indicated that the incidence rate of HDCP was 9.4% in China and 7%-12% in foreign countries, which of preeclampsia was 5-10% at present. Women with preeclampsia are very likely to develop cardiovascular and kidney disease Forwards. So far, preeclampsia are a major cause of morbidity and mortality of maternal and infant. The effectively predict, diagnosis, treatment and prevention in preeclampsia have not only get lots of attention from obstetrics, but also been a focus in the study of pathological obstetrics all over the world.Gestational hypertension and preeclampsia were the most common types in HDCP. The majority of patients has no history of hypertension before pregnancy. Generally, the clinical manifestations were characterized by hypertension and (or) albuminuria. Because of the influence of various external factors on blood pressure, so albuminuria had became the important indicator on the severity of HDCP. The occurrence of albuminuria marks kidney injury which is one of the most affected organ involvement in preeclampsia. Detection analysis of renal function and urine related biochemical indicators had important significance to the treatment of preeclampsia. It was reported that albuminuria level was related index for prognosis of fetus and pregnant women. Kidney was the important organ of elimination in the body, meanwhile, albumin was the most protein in body fluids which molecular weight was 69000D and the minimal protein can through glomerular filtration membrane. Albumin filtered was almost absorbed in the renal proximal convoluted tubule completely,therefore, urine albumin cannot be detected normally. Albuminuria present as protein concentration in the urine was increased when glomerular filtration membrane and renal tubular injuryed by kinds of pathogenic factors. Normal women during pregnancy would have physiologic albuminuria usually no more than 300 mg/day because of glomerular filtration rate (GFR) and renal plasma flow (RPF) had increased. However, women with HDCP would have pathological albuminuria due to GFR and RPF had decreased caused by reducing flow and renal vasospasm, in turn kidney lesion. There were significant correlation between the severity of HDCP and the amount with type of albuminuria. Albuminuria from selectived to non with HDCP worsened, which indicated glomerular and tubular injury by varying degrees.24-hour urinary protein quantitative was the major clinical test on the measurement of albuminuria. But there were lots of shortcomings such as time-consuming, difficult to separate, insufficient standard, disturbance, poor compliance, etc. It often takes 1-2 days for the patient to estimate disease condition and could be affected by the interference of vaginal secretions to result a false positive results. At the same time,since HDCP changing and moving quickly, the patient would appear great variety in one day, so clinicians need a more rapid and sensitive index to carries on the preliminary assessment on the severity of the disease. Trace albuminuria, also known as proteinuria or microalbuminuria, refers to the urinary albumin rate of excretion in between 30-300 mg/24 h. Previous study showed that microalbuminuria was the sensitive indexes of renal vascular endothelial dysfunction at early stage. Some scholars believed that microalbuminuria can be used as early diagnostic indicators of preeclampsia on account of that appeared before large amounts of albuminuria. The detection of albuminuria affected by amount and concentration of urine due to urinary albumin excretion rate (UAER) having difference on time. In recent years, random urinary albumin/creatinine ratio was used to evaluate the level of proteinuria. UAER could not be reflected by random urinary albumin accurately, while creatinine cleaning rate(Ccr) constant relatively. ACR widely used to detect protein quantitative in clinical kidney disease currently, which has the advantage of timesaving, simple, convenient, good compliance, and can accurately reflect the condition of urine protein excretion in 24 hours, for eliminating the influence of time and urine concentration. In 2002, the American National Kidney Fondation(NKF) formulate Kidney Disease Outcome Quality Initiative guidelines(K/DOQI) to recommend using urinary albumin/creatinine ratio(ACR) instead of 24 h urine protein quantitative as detection method for urinary protein excretion. Standards of Medical Care in Diabetes—2011 of American Diabetes Association(ADA) also explicitly put forward ACR for diabetic nephropathy patients as urinary protein detection. Society of Obstetricians and Gynaecologists of Canada (SOGC), American Society of Hypertension (ASH) had taken ACR>30mg/mmol or 24 h urine protein quantitative>300 mg as one of the standard for diagnosis of preeclampsia. Society of Obstetric Medicine of Australia and New Zealand(SOMANZ) recommend using ACR instead of 24 h urine protein quantitative for preeclampsia diagnosis. There existed no clinical epidemiology researches with multicentre and large-scale in China recently.The disease progression of preeclampsia was rapid, and the etiology of that still unknown. The starting symptoms of preeclampsia could be just as hypertension or albuminuria alone. Part of patients with severe had no clinical manifestations of high blood pressure or albuminuria prior to the onset of illness,others with only laboratory abnormalities, such as hypoalbuminemia, hyperuricemia,β 2-hypermicroglobulin on the sub-clinical stage. How to establish a method of prediction and diagnosis of preeclampsia, has become a key link in the process of prevention and treatment of eclampsia. In our subject,584 women with hypertensive disorders complicating pregnancy including 169 gestational hypertension,205 mild preeclampsia,173 severe preeclampsia,37 chronic hypertension complicating pregnancy were collected from December 2012 to December 2013 in xiaolan people’s hospital. Tracked the pregnancy outcome of the random selection of normal pregnant women acceptted antenatal examination in our hospital at the same time,87 suffered from hypertensive disorders complicating pregnancy and 2038 enjoyed a good ending. Determined random spot albuminuria to creatinine ratio(ACR) and 24 hours urinary protein, analyzed the correlation of them, to discuss the diagnostic and predictive value of ACR in women with hypertensive disorders complicating pregnancy. All these were intended to provide a simple, convenient and reliable testing methods for the early determination of status estimating, condition monitoring and prognosis predicting of HDCP. Starting from this study, we could judge condition and predict development of HDCP through testing random urinary albumin/creatinine ratio,routine blood and urine, albumin, blood urea nitrogen, creatinine, glucose, lipid values. In the further research, we should select more pregnant women in much more center to find a economic and feasible way for diagnostic and predictive of HDCP.This paper consist of 2 chapters, as follows:Chpterl:The clinical significance of random spot albuminuria to creatinine ratio at different gestational stages in women with and without hypertensive disorders complicating pregnacy1. Objective:Determined random spot albuminuria to creatinine ratio(ACR) at different gestational stagesin in women with and without hypertensive disorders complicating pregnacy, analyzing the characteristic of change in ACR, to explore the predictive and diagnostic value of ACR in women with hypertensive disorders complicating pregnancy.2. Methods:584 women with hypertensive disorders complicating pregnancy including 169 gestational hypertension,205 mild preeclampsia,173 severe preeclampsia,37 chronic hypertension complicating pregnancy,87 prehypertensive disorders complicating pregnancy and 2038 normal pregnant women were collected over the same timeAll of the women were divided into four group according to different gestational age as<20 weeks,20-27+6 weeks,28-35+6 weeks,>36 weeks.ACR were determined in all the cases.3. Results:(1) ACR in preeclampsia group were significantly higher than other groups, among them the severe higher than the mild, while normal group were lower than other groups, and no significant differentn in the groups except preeclampsia or normal.(2) ACR in severe preeclampsia group at second-trimester were significantly higher than late trimester, however, the results of the normal group were on the contrary, and no significant differentn in the other groups throughout the pregnancy.(3) ACR in preeclampsia group were significantly higher than the other groups throughout the pregnancy, which in normal group lower than prehypertensive disorders complicating pregnancy group, and no significant differentn in the other groups throughout the pregnancy.Chpter2:predictive and diagnostic value of random spot albuminuria to creatinine ratio in women with hypertensive disorders complicating pregnancy1. Objective:Determined random spot albuminuria to creatinine ratio(ACR),24 hours urinary protein and other biochemical indicators in normal pregnant women and hypertensive disorders complicating pregnancy, analyzed the correlation of them, to discuss the predictive and diagnostic value of ACR in women with hypertensive disorders complicating pregnancy.2. Methods:Tracked the pregnancy outcome of the random selection of normal pregnant women acceptted antenatal examination in our hospital,87 suffered from hypertensive disorders complicating pregnancy and 2038 enjoyed a good ending. 584 women with hypertensive disorders complicating pregnancy including 169 gestational hypertension,205 mild preeclampsia,173 severe preeclampsia and 37 chronic hypertension complicating pregnancy were collected over the same time.ACR, routine examination of blood and urine, liver and kidney function, fasting plasma glucose, glycated hemoglobin,24 hours urinary protein were determined in normal pregnant women.ACR,24 hours urinary protein, routine examination of blood and urine, coagulative function, liver and kidney function, fasting plasma glucose, glycated hemoglobin, insulin, C-Peptide, lipids were determined in women with hypertensive disorders complicating pregnancy.ACR and result of accessory examinations were compared in all the cases. Bivariate correlation analysis was used to analyze the relationship of ACR,24 hours urinary protein quantitative and other biochemical indicators. To identify the independent risk factor of hypertensive disorders complicating pregnancy on logistic regression analysis. Receiver operating characteristic (ROC) curve was used to analyze the sensitivity, specificity and optimal cut off value of ACR for predicting and diagnosing hypertensive disorders complicating pregnancy.3. Results:(1) Compared with normal pregnant women, ACR, age, fasting plasma glucose, urea nitrogen, serum creatinine, glycated hemoglobin were significantly higher in women with prehypertensive disorders complicating pregnancy, however, serum albumin, total protein, red blood cells were significantly lower.24 hours urinary protein quantitative had no significant different.(2) In women with hypertensive disorders complicating pregnancy, ACR,24 hours urinary protein quantitative, blood urea nitrogen, serum creatinine, uric acid, total cholesterol, low density lipoprotein cholesterol (BUN, Cr, UA, TC, LDL) were significantly higher in women with severe preeclampsia, however, platelet (PLT), serum albumin, total protein were significantly lower. In women with mild preeclampsia group, ACR,24 hours urinary protein quantitative, UA was significantly higher, while serum albumin significantly lower than that in the other two groups.(3) Age, gestational weeks, ACR, red blood cells, fasting plasma glucose, serum creatinine, total protein were the independent risk factor of hypertensive disorders complicating pregnancy.(4) In women with prehypertensive disorders complicating pregnancy, there was positive correlation between the ACR and 24 hours urinary protein quantitative, r=0.37, P=0.002. There was no correlation between the ACR and other biochemical indicators. In women with hypertensive disorders complicating pregnancy, there were positive correlation between the ACR and 24 hours urinary protein quantitative, urea nitrogen, serum creatinine, UA, D-dimer, TC, LDL (r=0.94,0.37,0.35,0.61,0.12, 0.33,0.31, P<0.001,<0.001,<0.001,<0.001,=0.003,<0.001,<0.001), while negative correlation between ACR and serum albumin, total protein, PLT (r=-0.46,-0.40,-0.12, P<0.001,<0.001,=0.003)(5) Area under curve (AUC), sensitivity, specificity and optimal cut off value of ACR for predicting hypertensive disorders complicating pregnancy were 0.787,0.78, 0.63,1.46mg/mmol. Area under curve (AUC), sensitivity, specificity and optimal cut off value of ACR for predicting gestational hypertension, mild preeclampsia, severe preeclampsia (24 hours urinary protein quantitative^ 2g) severe preeclampsia (24 hours urinary protein quantitative≥5g) were 0.823,0.89,0.61,1.44mg/mmol,0.988, 0.97,0.96,10.48 mg/mmol,0.978,0.97,0.88,39.84 mg/mmol,0.973,0.95,0.87, 94.91 mg/mmol separately. Conclusion 1. ACR in women with prehypertensive disorders complicating pregnancy hadappeared to increase at second-trimester, in women with severe preeclampsiacharacterized with early onset and serious conditions significantly higher. ACR was suggested to be monitored regularly from mid-pregnancy for identifying the pregnant women with high risk.2. There was positive correlation between ACR and 24 hours urinary protein quantitative, compared with the latter and urine routines, ACR provided the more sensitive pathway of early prediction in the hypertensive disorders complicating pregnancy.3. There was highly positive correlation between ACR and 24 hours urinary protein quantitative in the prehypertensive and hypertensive disorders complicating pregnancy. ACR could be used for diagnosing and estimating the severity degree of hypertensive disorders complicating pregnancy.