CN112034189B - Application of endothelin-1 as marker for evaluating asymptomatic cardiovascular organ damage of primary chronic kidney disease patient - Google Patents
Application of endothelin-1 as marker for evaluating asymptomatic cardiovascular organ damage of primary chronic kidney disease patient Download PDFInfo
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
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Abstract
The invention discloses application of endothelin-1 as a marker for evaluating asymptomatic cardiovascular organ damage of a patient with primary chronic kidney disease. By detecting the level of endothelin-1 in an isolated sample of a patient with primary chronic kidney disease, asymptomatic cardiovascular organ damage occurs when the value of endothelin-1 is > 1.60 pg/mL. Since endothelin-1 of the present invention can evaluate the risk of an asymptomatic cardiovascular damage event and the presence of an event in a primary chronic renal patient with good accuracy, it can be used as a risk factor for evaluating a chronic renal patient who finds a cardiovascular damage event in a primary chronic renal patient at an early stage, and can predict and prevent the occurrence of a cardiovascular event in a chronic renal patient, and can effectively intervene in cardiovascular organ damage at an early stage.
Description
Technical Field
The invention belongs to the technical field of endothelin-1, and particularly relates to application of endothelin-1 as a marker for evaluating asymptomatic cardiovascular organ injury of a patient with primary chronic renal disease.
Background
The prevalence of chronic kidney disease is increasing, and cardiovascular diseases are one of the main causes of death in patients with chronic kidney disease. As an intermediate state between health and cardiovascular disease, "asymptomatic cardiovascular organ damage" is of high interest, especially in the risk, prediction of cardiovascular events.
At present, the definition and detection means of the 'asymptomatic cardiovascular organ injury' are clear, but the indexes for effectively predicting the 'asymptomatic cardiovascular organ injury' are lacked, and the research on the transition period from health to the 'asymptomatic cardiovascular organ injury' is still insufficient. There is therefore a need for a means to predict "asymptomatic cardiovascular organ damage".
On the other hand, endothelial cell dysfunction underlies vascular injury, and detection of its biomarkers can predict cardiovascular events and prognosis of cardiovascular events. Endothelin (ET-1) and its receptor are widely expressed in macrophages, vascular smooth muscle cells and fibroblasts. Studies on the mechanisms of several diseases have shown that it plays an important role in the dysfunction, proliferation, inflammation of renal podocytes, circulating leukocytes and vascular endothelial cells.
The technical defects of 'asymptomatic cardiovascular organ damage' in the prior art are poor in accuracy and directness, and are specifically represented as follows: (1) The individual needs to complete the examination including heart color ultrasound, artery color ultrasound, electrocardiogram and the like, so that the doctor can make comprehensive judgment. (2) The accuracy of the above-mentioned inspection method is easily influenced by different instruments and operators. The prior art is therefore very limited for assessing "asymptomatic cardiovascular organ damage".
The prior art also has hysteresis and is simple and convenient. Examinations such as heart color ultrasound, artery color ultrasound, electrocardiogram and the like generally require more manpower and time to complete, so that body fluid detection including serum and urine is a more common choice for the group of "asymptomatic" or for the group of general physical examinations. The early warning of the asymptomatic cardiovascular organ damage is difficult to be given by the examination of heart color Doppler ultrasound, artery color Doppler ultrasound, electrocardiogram and the like only after the occurrence of definite symptoms.
Therefore, in the case of predicting the asymptomatic cardiovascular organ damage in the absence of an effective means, it is important to research the risk factors for evaluating the asymptomatic cardiovascular organ damage.
Disclosure of Invention
The invention aims to provide application of endothelin-1 as a marker for evaluating asymptomatic cardiovascular organ damage of patients with primary chronic renal disease.
The above object of the present invention can be achieved by the following technical solutions: use of endothelin-1 as a marker for the evaluation of asymptomatic cardiovascular organ damage in patients with primary chronic kidney disease.
The invention carries out relevant research on the endothelin-1 (ET-1) concentration as an evaluation index of the asymptomatic cardiovascular organ injury of the primary chronic kidney disease patient, and the result shows that the endothelin-1 (ET-1) is relevant to the asymptomatic cardiovascular organ injury of the primary chronic kidney disease patient, and the increase of the endothelin-1 (ET-1) concentration can be used as an evaluation factor of the asymptomatic cardiovascular organ injury of the primary chronic kidney disease patient.
Therefore, in the absence of effective means for predicting asymptomatic cardiovascular organ damage, it is important to evaluate asymptomatic cardiovascular organ damage by the detection of endothelin-1 (ET-1).
Further, the process of evaluating asymptomatic cardiovascular organ damage in patients with primary chronic kidney disease according to the present invention is as follows:
(1) Setting a healthy control group, a subgroup 1 and a subgroup 2, wherein the subgroup 1 is a primary chronic kidney disease patient without clinical cardiovascular and cerebrovascular diseases and asymptomatic cardiovascular organ injury, and the subgroup 2 is a primary chronic kidney disease patient without clinical cardiovascular and cerebrovascular diseases and asymptomatic cardiovascular organ injury;
(2) Testing the concentration levels of endothelin-1 in three groups of in-vitro biological samples by adopting an enzyme immunoadsorption method;
(3) Performing statistical analysis on the endothelin-1 in each group;
(4) Establishing a Logistic regression model, judging the correlation between endothelin-1 and asymptomatic cardiovascular organ injury, and obtaining the threshold value of endothelin-1 when the asymptomatic cardiovascular organ injury occurs.
Preferably, the test results show that: in the step (3), the healthy control group and the subgroup 1 have no statistical significance, the subgroup 1 and the subgroup 2 have statistical difference, and the endothelin-1 is related to the change of the asymptomatic cardiovascular organ injury, namely, the endothelin-1 is a biological marker of the occurrence of the patients with the primary chronic kidney disease accompanied with the occurrence of the asymptomatic cardiovascular organ injury.
Preferably, in step (4), SPSS 22.0 software is used for data statistics, and P <0.05 is defined as statistically significant, and when the value of endothelin-1 is greater than 1.60pg/mL, no symptom of cardiovascular organ damage is caused.
Preferably, the isolated biological sample in step (2) is a non-liquid biological sample of each group of isolated tissue or isolated cells, or the isolated biological sample is isolated serum or isolated urine of each group.
More preferably, the ex vivo biological sample is an ex vivo serum of each group.
Preferably, the centrifuged serum sample is obtained by centrifuging the ex vivo venous blood.
Preferably, the primary chronic kidney disease stage 4-5 is described in the clinical practice guidelines for chronic kidney disease and dialysis (2002 edition)/original book of the U.S. NKF-K/DOQI working group; wang Haiyan and Wang Mei Ming Ying.
Specifically, the primary chronic kidney disease patient in the step (1) meets the following conditions: diagnosing the primary chronic kidney disease in 4-5 stages, wherein the primary chronic kidney disease in 4-5 stages refers to: the eGFR of the tested individual is less than 30 mL/min.1.73 m 2 The time is more than or equal to 3 months, and the need of immediate dialysis replacement treatment is avoided, the acute infectious diseases and tumors are not combined, and secondary nephropathy is excluded, wherein the secondary nephropathy comprises lupus nephritis, diabetic nephropathy, henoch Schonlein purpura nephritis, ANCA nephritis or obstructive nephropathy.
Preferably, refer to the discussion of guidelines for treating hypertensive heart disease of European college/European college in 2013. The asymptomatic cardiovascular organ damage in step (1) meets one of the following: a) Electrocardiogram: prolongation of QT interval, or high left ventricular voltage, or left ventricular hypertrophy; b) Heart color Doppler ultrasound: E/E' Ratio is more than or equal to 13, or the diameter of the left atrium is more than 53mm, or the volume of the left ventricle (LVEDVi) > 97mL/m 2 (ii) a c) Carotid artery color ultrasound: the thickness of the middle carotid intima layer is more than 0.9mm.
Preferably, the clinical cardiovascular and cerebrovascular diseases in step (1) include myocardial infarction, acute coronary syndrome, coronary atherosclerotic heart disease, heart failure, arterial dissection, cerebral infarction or cerebral hemorrhage.
The application in the application is a method for assisting a physician to evaluate asymptomatic cardiovascular organ damage of a patient with primary chronic kidney disease, and does not comprise the diagnostic action of the physician. In addition, data may be collected for evaluation of asymptomatic cardiovascular organ damage in patients with primary chronic kidney disease.
Compared with the prior art, the invention has the following advantages: the endothelin-1 in the invention can evaluate the risk of asymptomatic cardiovascular injury event and the existence of disease of a primary chronic kidney disease patient with good precision, thus being used as an evaluation risk factor of the chronic kidney disease patient for finding the cardiovascular injury event of the primary chronic kidney disease patient at an early stage, being capable of predicting and preventing the occurrence of the cardiovascular event of the chronic kidney disease patient and effectively intervening cardiovascular organ injury at an early stage, therefore, the endothelin-1 in the invention as a marker has the effects of early diagnosis, early intervention, prevention of the occurrence of the cardiovascular injury event, improvement of life quality, reduction of medical cost and the like for the primary chronic kidney disease patient.
Drawings
FIG. 1 is a comparison of endothelin-1 concentrations between groups in example 1 of the present invention;
FIG. 2 is a Receiver operating characteristic curve (ROC) of endothelin-1 (ET-1) in example 1 of the present invention; ( ROC curve of ET-1; calculated using the john index, the threshold was > 1.60pg/ml, sensitivity: 73.7%, false positive rate: 8.3 percent. )
FIG. 3 is a vector image of the structural formula of endothelin-1 in example 1 of the present invention.
Detailed Description
As a test procedure for an event of asymptomatic cardiovascular organ damage in a primary chronic kidney disease patient according to the present invention (hereinafter, simply referred to as "the measurement method of the present invention"), there is no particular limitation mainly on evaluating asymptomatic cardiovascular organ damage in a chronic kidney disease patient (wherein, diagnostic actions by physicians are excluded) by concentration of Endothelin-1 (hereinafter, these are collectively referred to as "ET-1") in a biological sample collected from a subject (provider), and, in addition, as a biomarker for asymptomatic cardiovascular organ damage in a primary chronic kidney disease patient according to the present invention (hereinafter, simply referred to as "the biomarker of the present invention"), here, "asymptomatic cardiovascular organ damage in a primary chronic kidney disease patient" includes evaluation of asymptomatic cardiovascular organ damage. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by manufacturers, and are all conventional products available on the market.
The invention passes the examination of the ethical committee of the traditional Chinese medicine of Guangdong province, and all research objects sign informed consent. The study related to healthy people is from the group of healthy community people in nephropathy laboratories of traditional Chinese medicine of Guangdong province. All patients with Chronic Kidney Disease (CKD) were enrolled according to KDIGO 2012 guideline for assessment and management of Chronic kidney disease.
Examples of the biological sample include non-liquid samples such as tissues, cells, and organs; in the present example, a sample of isolated blood (serum) is used as a liquid sample such as blood and urine.
In the prediction method of the present invention, endothelin-1 (Endothelin-1) as a detection target is a compound (CAS registry number: 117399-94-7) shown in FIG. 3 as a vector image of the structural formula.
Example 1
The correlation analysis of endothelin-1 (ET-1) in serum for asymptomatic cardiovascular organ damage in patients with primary chronic renal disease was performed by the following assay.
1. Method of producing a composite material
1.1 inclusion and exclusion criteria
Eligible patients were 18 years or older at the time of enrollment, primary chronic renal disease stage 4-5 patients who did not require immediate dialysis and kidney transplant therapy, and no immediate dialysis replacement therapy was required, with no concomitant acute infectious disease and tumor. Excluding secondary kidney diseases including lupus nephritis, diabetic nephropathy, henoch-Schonlein purpura nephritis, ANCA nephritis or obstructive nephropathy.
1.2 packet Standard
Chronic kidney disease patients (hereinafter CKD) were divided into 2 groups, subgroup 1 (no clinical cardiovascular and cerebrovascular disease and no "asymptomatic cardiovascular organ damage") and subgroup 2 (no clinical cardiovascular and cerebrovascular disease with "asymptomatic cardiovascular organ damage", hereinafter CKD + acd), according to the 2013 ESH/ESC hypertension treatment guidelines.
According to 2013 ESH/ESC guidelines for hypertension treatment, aCVD meets one of the following: E/E' ratio is more than or equal to 13, the diameter of the left atrium is more than 53mm, and the volume of the left ventricle (LVEDVi) > 97mL/m 2 Thickness of intima-media layer of carotid artery>0.9mm, abnormal electrocardiogram (prolonged QT interval, or high voltage in the left ventricle, or hypertrophy of the left ventricle).
The healthy control samples were from community physical examination population samples (health community population cohort in the renal disease laboratory, guangdong province).
The development of the tests, the sample collection and the detection all accord with the national clinical research standard, and all individuals sign informed consent after the ethical examination.
1.2 biological samples and data Collection
The biological sample is serum. Blood samples from patients with chronic kidney disease and healthy controls were stored at-80 ℃ in a refrigerator until they were taken at the time of measurement, and samples meeting the criteria were selected based on patient information.
And selecting a sample according to age and sex matching in the healthy control group.
Age, sex, biochemical index, etc. are recorded in the book.
Finally, 10 healthy control groups, a subgroup 1 (CKD) 12 and a subgroup 2 (CKD + aCVD) 38 are included.
1.3.1 serum ET-1 measurements
The concentration of serum (ET-1) was determined by enzyme-linked immunosorbent assay (ELISA). The method specifically comprises the following steps:
(1) Sample preparation: taking out the sample from a refrigerator at minus 80 ℃, placing the sample in a normal temperature, and taking a proper amount of serum for ELISA detection of ET-1 after dissolving.
(2) Preparing a reagent:
1) Washing liquid: weighing 20mL of Washing buffer (25X), adding into 480mL of distilled water, and preparing 500mL of Washing liquid;
2) Luminescent liquid: mixing 10mL of each of the color developing solution A and the color developing solution B, storing in a dark place, using the mixture as a preparation, and using the mixture within 15 minutes after the preparation;
3) And (3) standard substance: adding distilled water to prepare a standard substance of 250 pg/mL;
4) Calibration of the diluent: measuring 5mL of a correction agent, and adding the correction agent into 20mL of distilled water for dilution;
(3) ELISA operation steps: the experimental operation flow is strictly carried out according to the instruction, and each sample and each standard product are subjected to multi-hole detection. Add 75. Mu.L of serum or standard to the wells and 150. Mu.L of primary antibody, place on the shaker at 500. + -. 50rmp, incubate at room temperature for 1 hour. Pouring off the sample and the antibody, washing the plate with a prepared washing solution, adding 400 mu L of the washing solution into each hole, shaking for 40s, pouring off the liquid, repeating for three times, and beating off the redundant washing solution on a clean paper towel after the plate is washed for the last time to reduce the washing solution residue as much as possible. Add 200 u L secondary antibody, room temperature in the table incubation for 3 hours, after the repeated plate washing process, the last washing plate, each hole add 200 u L substrate, room temperature in the dark incubation for 30 minutes. And finally, adding 50 mu L of color development liquid into each hole, slightly shaking and uniformly mixing, placing into an enzyme-labeling instrument for detection, detecting the absorbance value under the light of 450nm, and correcting under the light of 540-570 nm.
(4) ET-1 concentration calculation: a standard curve was constructed using a four parameter method and the ET-1 concentration was calculated from the OD of each sample in pg/mL.
1.3.2 measurement of other detection indices
Other detection indicators include: syndecan-1 (hereinafter, SDC-1), hyaluronan (hereinafter, HA), thrombomodulin (hereinafter, TM), heptan sulfate (hereinafter, HS), and E-Selectin (hereinafter, sE). The index concentration determination adopts an enzyme-linked immunosorbent assay, and the specific steps are the same as the measuring steps of 1.3.1ET-1.
1.4 statistical analysis
The measurement data are expressed as "mean. + -. Standard deviation", and the count data are expressed as number of cases or composition ratio. Baseline characteristics and measurement data were compared for each group of patients using one-way anova. The correlation was judged by Logistic regression model and data statistics was performed by SPSS 22.0 software. P <0.05 was defined as statistically significant.
2. Results
2.1 sets of baseline characteristics, see Table 1 below.
TABLE 1 Baseline characteristics Table for each group
Table 1 shows the basic data for each group, and the statistical differences are the differences compared together for 3 groups. Therefore, doctors cannot judge whether the CKD patient has the asymptomatic cardiovascular organ damage only through the indexes of blood fat, blood pressure and the like which are common in clinic because the blood pressure history and the blood fat of the CKD patient are higher than those of normal people whether the asymptomatic cardiovascular organ damage exists or not.
2.2 comparison of Each index between healthy control and subgroup 1 (CKD)
By comparison, ET-1 was not statistically significant in subgroup 1 (CKD) versus healthy controls, suggesting that CKD did not result in a change in the concentration of ET-1, see table 2 below.
TABLE 2 comparison of indices between healthy control and subgroup 1 (CKD)
| Healthy control group (n = 10) | Subgroup 1 (CKD, n = 12) | P value | |
| Endothelin-1(ET-1,pg/mL) | 1.26±0.41 | 1.378±0.21 | 0.385 |
| Age (year of age) | 64.4±10.97 | 56.42±4.50 | 0.032 |
| Sex [ male, n (%)] | 4(40) | 4(33.3) | 0.76 |
| eGFR(mL/min·1.73m 2 ) | 82.66±20.21 | 24.31±4.27 | ＜0.0001 |
| Hyperuricemia [ n (%)] | 0 | 5(41.67) | 0.019 |
| Hypertension [ n (%)] | 0 | 5(41.67) | 0.019 |
| BMI | 18.67±0.859 | 21.21±3.43 | 0.236 |
| Low density lipoprotein (LDL, mmol/L) | 2.61±0.96 | 3.42±1.51 | 0.233 |
2.3 comparison of Each indicator for subgroup 1 (CKD) with subgroup 2 (aCVD + CKD)
ET-1 is statistically different between subgroup 1 (CKD) and subgroup 2, see Table 3 below.
TABLE 3 subgroup 1 (CKD) vs subgroup 2 (aCVD + CKD) indices
In subgroup 1 (CKD) and 2 (acd + CKD) comparisons, there were no differences in traditional cardiovascular risk factors, including LDL, hypertension prevalence, and ET-1 statistical differences (P = 0.007); in conclusion, under the premise that the CKD basic diseases and the traditional cardiovascular risk factors of the two groups are similar, aCVD is used as a variable between the two groups, and ET-1 shows clear statistical difference between the two groups; when applicants have determined that some other indicators in the ex vivo biological samples of the two groups, such as sE, HA, TM, etc., are likely to reflect cardiovascular disease, all of these alternative indicators do not reflect the presence of acdd in CKD patients, we only proposed ET-1 as the best marker for assessing asymptomatic cardiovascular organ damage in patients with primary chronic kidney disease, as detailed in table 3 and fig. 2 above.
2.4 building Logistic regression model to judge the correlation between ET-1 and aCVD
In subgroup 1 (CKD) and subgroup 2 (aCVD + CKD) comparisons, there was no difference in classical cardiovascular risk factors, including LDL, hypertension prevalence, and a statistical difference in ET-1 (P = 0.007).
In summary, while excluding the effects of CKD and traditional cardiovascular risk factors, acd is used as a variable between two groups, the ET-1 difference between the two groups correlates with the change in acd, and other measures do not reflect the presence of acd in CKD patients. Therefore, ET-1 is the best marker, see Table 3 above.
The pair of endothelin-1 concentrations between groups is shown in figure 1. As can be seen from fig. 1, the endothelin-1 concentration was gradually increased in healthy controls, subgroup 1 and subgroup 2 (1.26 ± 0.41vs1.378 ± 0.21vs1.938 ± 0.674, p = 0.001).
The concentration of the marker is not different between the healthy control group and the subgroup 1, the subgroup 2 is higher than the subgroup 1 and has statistical difference, the marker is considered to be the optimal marker when the two indexes are met, and the other 5 indexes do not meet the conditions, so the marker is excluded.
A Logistic regression model was established, and ET-1 was statistically different between subgroup 1 and subgroup 2 (P = 0.008). ET-1 is a biological marker of the occurrence of aCVD in CKD patients, see Table 4 below.
TABLE 4 Logistic regression model
Remarking: OR: odds ratio, CL: a confidence interval.
The Receiver operating characteristic curve (ROC) of endothelin-1 (ET-1) is a statistical method for comparing the performance of new diagnostic standards with gold standards. The method has the advantages of simplicity, intuition, capability of observing the accuracy of the analysis method through the graphic representation and capability of judging by naked eyes. Through the ROC curve, the capability of identifying the performance of any limit value can be found. Namely, the probability of false positive and false negative of each value is judged, and the value with the lowest false positive and false negative is taken as the optimal threshold value. In the model shown in FIG. 2, the predicted optimal value of endothelin-1 was 1.60pg/mL as calculated by the Jordan index, the predicted sensitivity was 73.7% and the false positive rate was 8.3%. Therefore, selection of an endothelin-1 threshold > 1.60pg/mL predicts the onset of subclinical cardiovascular injury.
Therefore, endothelin-1 can be used for evaluating asymptomatic cardiovascular injury and vascular injury of patients with primary chronic kidney diseases. In particular, the occurrence of asymptomatic cardiovascular organ damage in patients with primary chronic kidney disease (stage 4-5) can be evaluated and further predicted.
According to the invention, through the biological data of 38 patients with primary chronic kidney diseases and cardiovascular events, 12 patients with chronic kidney diseases without cardiovascular events and 10 healthy people, correlation analysis and a binary Logistic regression model are adopted to obtain an Endothelin-1 (Endothelin-1, ET-1) which is a relevant index possibly related to the occurrence of the cardiovascular events of the patients with primary chronic kidney diseases. The level of the indicator can be detected by a biological sample from the subject using an immunoenzyme-linked immunosorbent assay. Screening the people with high risk of asymptomatic cardiovascular organ damage through the ET-1 concentration level. Early intervention in high risk patients to prevent cardiovascular events.
In conclusion, it is obvious to those skilled in the art from the present disclosure that asymptomatic cardiovascular organ damage in chronic renal patients can be evaluated and further predicted by measuring the serum concentration of ET-1 and using ET-1 as a marker.
Furthermore, the marker of the invention can be used for early detection and early intervention of asymptomatic cardiovascular organ injury of chronic kidney disease patients, prevention of occurrence of the asymptomatic cardiovascular organ injury and the like.
Although the invention has been described in detail hereinabove with respect to a general description and specific embodiments thereof, it will be apparent to those skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (3)
1. The use of endothelin-1 in the manufacture of a marker detection reagent for the assessment of asymptomatic cardiovascular organ damage in patients with primary chronic kidney disease;
the procedure for evaluating asymptomatic cardiovascular organ damage in patients with primary chronic kidney disease is as follows:
(1) Setting a healthy control group, a subgroup 1 and a subgroup 2, wherein the subgroup 1 is a primary chronic kidney disease patient without clinical cardiovascular and cerebrovascular diseases and asymptomatic cardiovascular organ injury, and the subgroup 2 is a primary chronic kidney disease patient without clinical cardiovascular and cerebrovascular diseases and asymptomatic cardiovascular organ injury;
(2) Testing the concentration level of endothelin-1 of three groups of in-vitro biological samples by adopting an enzyme immunoadsorption method;
(3) Performing statistical analysis on the endothelin-1 in each group;
(4) Establishing a Logistic regression model, judging the correlation between endothelin-1 and asymptomatic cardiovascular organ injury, and obtaining the threshold value of endothelin-1 when the asymptomatic cardiovascular organ injury occurs;
the primary chronic kidney disease patient in the step (1) meets the following conditions: diagnosing the primary chronic kidney disease in 4-5 stages, wherein the primary chronic kidney disease in 4-5 stages refers to: the eGFR of the tested individual is less than 30 mL/min.1.73 m 2 The time is more than or equal to 3 months, and the need of immediate dialysis replacement treatment is avoided, the acute infectious diseases and tumors are not combined, and secondary nephropathy is eliminated, wherein the secondary nephropathy comprises lupus nephritis, diabetic nephropathy, henoch Schonlein purpura nephritis, ANCA nephritis or obstructive nephropathy;
the asymptomatic cardiovascular organ damage in step (1) meets one of the following: a) Electrocardiogram: prolongation of QT interval, or high left ventricular voltage, or left ventricular hypertrophy; b) Heart color Doppler ultrasound: E/E' Ratio is more than or equal to 13, or the diameter of the left atrium is more than 53mm, or the volume of the left ventricle is more than 97mL/m 2 (ii) a c) Carotid artery color ultrasound: the thickness of the middle carotid intima layer is more than 0.9mm;
in the step (2), the isolated biological samples are non-liquid biological samples of each group, or the isolated biological samples are isolated serum or isolated urine of each group;
in step (4), SPSS 22.0 software is used for data statistics, and P <0.05 is defined as having statistical significance, and when the value of endothelin-1 is greater than 1.60pg/mL, the result is asymptomatic cardiovascular organ injury.
2. Use according to claim 1, characterized in that: in the step (3), the healthy control group and the subgroup 1 have no statistical significance, the subgroup 1 and the subgroup 2 have statistical difference, and the endothelin-1 is related to the change of the asymptomatic cardiovascular organ injury, namely, the endothelin-1 is a biological marker of the occurrence of the patients with the primary chronic kidney disease accompanied with the occurrence of the asymptomatic cardiovascular organ injury.
3. Use according to claim 1, characterized in that: the clinical cardiovascular and cerebrovascular diseases in the step (1) comprise myocardial infarction, acute coronary syndrome, coronary atherosclerotic heart disease, heart failure, arterial dissection, cerebral infarction or cerebral hemorrhage.
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| EP2843056A1 (en) * | 2013-08-30 | 2015-03-04 | Gendiag.exe, S.L. | Risk markers for cardiovascular disease in patients with chronic kidney disease |
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| EP2843056A1 (en) * | 2013-08-30 | 2015-03-04 | Gendiag.exe, S.L. | Risk markers for cardiovascular disease in patients with chronic kidney disease |
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