Wu-Bin Yao, Liang-Lan Shen, Yan Shen, Hua-Xing Huang

Department of Renal Medicine, Nantong First People's Hospital, Nantong, Jiangsu 226001

Keywords:TnI hs-CRP NT-proBNP Myocardial damage in uremia

ABSTRACT Objective: To study the clinical significance of troponinI (TnI), high sensitivity C reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the diagnosis of myocardial damage in uremia patients. Methods: 114 uremia patients treated in our hospital from January 2017 to February 2019 were selected. According to whether myocardial damage occurred, patients were divided into two groups including uremia group (63 cases) anduremia myocardial damage group (51 cases).50 hospitalized patients with non-chronic kidney disease and non-cardiovascular disease in our hospital were selected as control group.The levels of TnI, hs- CRP and NT-proBNP in 1, 3 and 7 days after admission were detected and compared.Meanwhile, the ecg indexes of left ventricular ejection fraction (LVEF) and Thickness of the posterior wall of the left ventricle (LVPWd) were recorded and compared. Person correlation was used to analyze the correlation between the levels of TnI, hs-CRP, NT-proBNP and ecg indexes including LVEF and LVPWd.COX regression analysis was used to analyze the independent riskfactors affecting the clinical prognosis of uremia patients. Results: The levels of TnI, hs-CRP, NT-proBNP in the three groups were significantly different on 1, 3, 7 days after admission. The levels of the three indexes (TnI, hs-CRP, NT-proBNP) in uremia combined with myocardial damage group and uremia group were decreased with treatment. However, the levels of the three indexes (TnI, hs-CRP, NT-proBNP) in uremia combined with myocardial damage group were the highest (P＜0.05).Compared with the other two groups, the LVEF of uremia combined with myocardial damage group was the lowest, while the LVPWd was the thickest, showing a significant difference (P＜0.05). There was negativecorrelation between LVEF and TnI, hs-CRP, NT-proBNP levels. However, LVPWd was positively correlated with TnI, hs-CRP and NT-proBNP levels (P＜0.05).COX regression analysis showed that TnI, hs-CRP, NT-proBNP levels, LVEF and LVPWd were the independent factors affecting the clinical prognosis of uremia patients Conclusion: The level of TnI, hs-CRP, NT-proBNP was dynamic change in the onset and treatment process in uremia combined with myocardial damage patients, which could be used for early diagnosis of uremia combined with myocardial damage.

1. Introduction

Uremia is a complex syndrome after kidney disease leads to the loss of kidney function, which can lead to a series of complications. Cardiovascular disease is the main cause of death for uremia patients [1], among which myocardial damage is the main complication, which seriously threatens the quality of life and safety of patients.Uremia is associated with a high incidence of myocardial damage, and its clinical symptoms lack specificity. However, since its diagnosis and the assessment of the severity of clinical symptoms are closely related to the prognosis of patients [2], it is of great clinical significance to search for early diagnostic indicators of uremia patients with myocardial damage.Troponin I (TnI) I is a sensitive indicator of myocardial function [3].Hypersensitive c-reactive protein (hs-crp) is a commonly used index in clinical bacterial infection detection.When myocardial damage, bacterial infection or increased inflammatory factors occurred [4], the level of n-terminal brain natriuretic peptide (nt-probnp) was significantly increased [5].At present, there are few studies on the significance of TnI, hs-crp and nt-probnp in the diagnosis of uremia myocardial damage. However, in clinical practice, some patients with uremia combined with myocardial damage may have increased levels of ntprobnp TnI. Therefore, this study is aimed at the clinical significance of TnI, hs-crp and nt-probnp in the diagnosis of uremia myocardial damage.

2. Materials and methods

2.1 General information

A total of 114 patients with uremia who were treated in our hospital from January 2017 to February 2019, aged 26-85 years, with an average age of (58.36±6.34) years, were selected as the study subjects.The patients were divided into two groups according to the occurrence of myocardial damage, the uremia group (63 cases) and the uremia myocardial damage group (51 cases). There were 33 males and 30 females in the uremia group, aged 31-79 years, with an average age of 57.69±6.18 years, a BMI of 23.78±2.08 kg/m2, and a course of disease of 5.16±0.78 years.There were 26 males and 25 females in the uremia myocardial injury group, ranging in age from 26 to 85 years, with an average age of 57.48±6.52 years, a BMI of 24.05±2.11 kg/m2, and a course of disease of 5.37±0.81 years.Meanwhile, 50 patients with non-chronic kidney disease and noncardiovascular disease hospitalized in our hospital during the same period were selected as the control group, including 28 males and 22 females, aged 30-78 years, with an average age of 55.65±6.11 years and a BMI of 23.65±2.31 kg/m2.There was no significant difference in the general clinical data of the three groups (P＞0.05).

Inclusion criteria: patients diagnosed with uremia [6].

Exclusion criteria :(1) patients with congenital heart disease, heart valve disease, cardiomyopathy, and atrial fibrillation;(2) patients with severe hypertension and hypertensive nephropathy;(3) patients with systemic lupus erythematosus;(4) patients with mental illness;(5) patients with combined tumors.

2.2 Diagnostic criteria for uremia myocardial damage [7]

(1) a history of chronic kidney disease;(2) congestive heart failure, arrhythmia, myocardial ischemia and other clinical manifestations;(3) laboratory examination indicated that there were elevated myocardial enzymes, dyslipidemia, and elevated parathyroid hormone.(4) abnormal ecg, cardiac ultrasound and chest radiograph;(5) myocardial intima biopsy showed myocardial damage.

2.3 Inspection method

Hs-crp: the fasting venous blood of the patients was collected at 3ml in the morning, placed in an anticoagulation-free tube, centrifugated at 3000r/min for 5min, the supernatant was taken, and the level of hs-crp was detected by immunoturbibimetry.

TnI, nt-probnp: the fasting venous blood of patients was collected at 3ml in the morning and placed in an EDTA anticoagulation tube. The serum TnI level and nt-probnp level were detected by enzyme linked immunosorbent assay (ELISA).

PHILIPS iE Elite color doppler ultrasound diagnostic instrument was used, and the probe frequency was set to 2～4 MHz. After the patient rested for 20min, the ultrasonic detection began. The left lateral supine position was taken, and the left lateral margin of the sternum was detected, and indicators such as left ventricular ejection score (LVEF) and left ventricular posterior wall thickness (LVPWd) were recorded.

2.4 Treatment

Two groups of patients on hemodialysis treatment, according to the patients all the indexes including blood pressure, electrolytes and water intake, dialysis adverse reaction factors such as comprehensive analysis, for hemodialysis patients with individualized ultrafiltration curve, at the same time must be in the process of dialysis for realtime monitoring of patients, especially in patients with blood glucose, blood pressure of the volatile, as well as the combination of patients with myocardial damage, should be closely monitored.For the patients in the uremia group with myocardial damage, the treatment plan to improve myocardial damage was given at the same time, such as heart strengthening, vasodilation, diuresis, control of blood pressure, and correction of calcium and phosphorus metabolic disorders.

2.5 Statistical methods

SPSS21.0 statistical software was used for data analysis. The measurement data were expressed as mean±SD.The enumeration data were expressed by rate or composition ratio.P＜0.05 was considered to be significant and statistically significant.Person correlation was used to analyze the correlation between TnI, hs-crp, nt-probnp levels and cardiac ultrasound indexes LVEF and LVPWd after admission.Univariate and multivariate Logisitic regression analysis and COX regression analysis models were constructed to analyze the independent risk factors affecting the clinical prognosis of uremia patients.

3. Results

3.1 Comparison of TnI, hs-crp and nt-probnp levels in the three groups

The levels of TnI, hs-crp and nt-probnp were significantly different in the three groups, of which uremia with myocardial damage was the highest in the group and the lowest in the control group (P＜0.05).With the improvement of treatment, the levels of TnI, hs-crp and ntprobnp in the uremia combined with myocardial damage group and the uremia group decreased significantly, which was statistically significant, but still significantly higher than the control group. The uremia combined with myocardial damage group was the highest (P＜0.05).The specific results are shown in table 1.

3.2 Comparison of cardiac hyperechoic LVEF and LVPWd levels at admission in the three groups

The levels of LVEF and LVPWd in the three groups were statistically significant (P＜0.05).The uremia group with myocardial damage had the lowest LVEF and the thickest LVPWd, while the control group had the highest LVEF and the thinest LVPWd.The specific results are shown in table 2.

Table 1 The comparison of level of TnI, hs-CRP, NT-proBNP for the three groups

Table 2 The comparison of level of LVEF, LVPWd for the three groups admitted to hospital

3.3 Correlation analysis of TnI, hs-crp and nt-probnp levels with LVEF and LVPWd

Person correlation was used to analyze the correlation between TnI, hs-crp and nt-probnp levels and cardiac ultrasound indexes LVEF and LVPWd after admission. The results showed that LVEF was negatively correlated with TnI, hs-crp and nt-probnp levels (P＜0.05).LVPWd was positively correlated with TnI, hs-crp and nt-probnp levels (P＜0.05).The specific results are shown in table 3.

Table 3 The correlation analysis between TnI, hs-CRP, NT-proBNP and LVEF, LVPWd

3.4 Regression analysis of the clinical prognosis of uremia patients

Death would be the end of the patient as classification variables (assignment 1, survival value 0), will the patient's survival as a continuous variable, the gender, age, BMI, course, TnI, hs CRP, NT - proBNP, LVEF, LVPWd as independent variables, respectively build Logisitic single factor and multiple factors regression analysis model, the results show that the hs - CRP, NT - proBNP, LVEF, LVPWd is is the independent factors affecting the clinical outcomes for patients with uremia.

For all the patients were followed for 5 months, 15 days, for an observation period, of which 13 people were killed and 101 people live, use of Kaplan Meier survival curve (assignment 1 death, survival value 0) for patients survival related factors including age, gender, BMI, course, TnI, hs - CRP, NT - proBNP, LVEF, LVPWd analysis (figure 1).Death would be the end of the patient as classification variables (assignment 1, survival value 0), will the patient's survival as a continuous variable, the gender, age, BMI, course, TnI, hs CRP, NT - proBNP, LVEF, LVPWd as independent variables, COX regression analysis model was constructed, and the results showed that TnI, hs CRP, NT - proBNP, LVEF, LVPWd is the independent factors influencing the clinical outcomes for patients with uremia, specific results are shown in table 4.

Table 4 The COX regression analysis of clinical prognosis for uremia patiens

Figure 1 The Kaplan-Meier curve for death group and survival group followed up for 5 months

4. Discussion

Uremia heart damage is a common clinical complication, mainly manifested as left ventricular structure and myocardial function changes, including coronary artery disease and cardiomyopathy.In recent years, studies have shown that uremia myocardial damage is mainly caused by non-specific cardiomyopathy caused by excessive pressure, excessive volume load, and disorders of the body's internal environment, and its clinical manifestations are mainly left ventricular hypertrophy, impaired left ventricular diastolic function, and even congestive heart failure in severe cases [8,9].

At present, the diagnosis of uremia myocardial damage is mainly to evaluate its morphological changes, myocardial systolic and diastolic function damage by echocardiography.Relevant studies found that the main clinical manifestations of uremia patients with myocardial damage were left ventricular hypertrophy and increased myocardial mass, and the left ventricular mass/volume ratio significantly increased [10], while the left ventricular mass and left ventricular volume assessed by echocardiography had a better effect on the evaluation of uremia myocardial damage [11].However, since the time of echocardiographic evaluation of relevant cardiac indicators of patients is relatively lagging, it can only be detected when the cardiac function of patients has serious changes, so this method is not favorable for early diagnosis and early intervention of uremia myocardial damage.Therefore, it is of great clinical significance to search for relevant indicators for early diagnosis of myocardial damage in uremia.

TnI is an important structural protein of cardiomyocytes and a specific marker of myocardial injury. When the heart is at normal level, the blood content is low.When myocardial injury destroys myocardial cell membrane, TnI can be isolated from myocardial cells and enter the interstitium, and the detection of myocardial injury is relatively specific and sensitive [12,13].However, there are few studies on the changes of TnI in uremia and uremia patients with myocardial damage.The results of this study showed that the TnI level of patients in the uremia group with myocardial damage at admission was the highest, and with the intervention of treatment, the TnI level of patients in the uremia group with myocardial damage and the uremia group was gradually reduced, but the TnI level of patients in the uremia group with myocardial damage was still the highest.In this study, the sensitive echocardiographic indexes LVEF and LVPWd of patients with myocardial damage were detected for evaluation, and the TnI level was correlated with LVEF and LVPWd. The results showed that LVEF was negatively correlated with TnI level.LVPWd was positively correlated with TnI (P＜0.05).Meanwhile, the patients were followed up for 5 months (every half month as a time period), and COX regression analysis was carried out on the outcome of the patients. The results showed that TnI was an independent factor affecting the clinical prognosis of uremia patients.The results indicate that TnI is of important clinical significance for early evaluation of myocardial damage in uremia and can predict the prognosis of patients.In addition, studies have found that TnI level of patients is significantly correlated with their re-hospitalization rate and mortality [14].Some patients are in a stable hemodynamic state in time, and if TnI level increases, the risk of death also increases [15].Study found [16], after acute pulmonary embolism, TnI levels increased significantly, may be due to pulmonary embolism after pulmonary artery pressure rise rapidly, right ventricular pressure rise suddenly, causing right ventricular expansion, cardiac muscle tension increases rapidly, causing coronary artery received oppression and cramps make perfusion to decrease, causing myocardial cell damage, characterized by TnI levels increased significantly, showed that elevated TnI levels may be associated with the right heart function damage.Therefore, the detection of TnI has important clinical significance.

Hs-crp is an acute reactive protein. When the body is stressed, hscrp can enhance the phagocytosis by activating the classical pathway through complement, and regulate the function of macrophages to clear the pathogen [17].Generally, hs-crp is used as an indicator of inflammation, infection, surgery and tumor in the body.But at the moment about the hs - CRP in uremia myocardial damage diagnostic significance of the study is less, this study result shows that the hospital patients with uremia combined myocardial damage group hs - the highest CRP levels, and with the intervention of treatment, although uremia combined myocardial injury group of hs - CRP levels are reduced on admission, but compared with the control group, uremia group is the highest.Correlation analysis of hs-crp level with LVEF and LVPWd showed that LVEF was negatively correlated with hs-crp level.LVPWd was positively correlated with hs-crp level (P＜0.05).COX regression analysis showed that hs-crp was an independent risk factor affecting the clinical prognosis of uremia patients.The results showed that hs-crp had important clinical significance for the early diagnosis of uremia myocardial damage, and the earlier the detection time, the better the treatment and prognosis of patients.

Nt-probnp is mainly synthesized and secreted by ventricular myocytes. When myocardial cell function is damaged, nt-probnp can be released in large quantities, which can reflect the severity of myocardial damage.Studies have found that nt-probnp can be used to assess the capacity load of uremia patients without symptoms of heart failure [18].Nt-probnp significantly decreased before and after hemodialysis in patients with uremia [19].Studies have shown [20] that nt-probnp significantly decreased in patients with uremia cardiomyopathy after relevant drug treatment.However, there are few studies on whether nt-probnp can early predict uremia myocardial damage. The results of this study show that the level of nt-probnp is the highest in patients with uremia combined with myocardial damage group at the time of admission. With the beginning of treatment, the level of nt-probnp in patients with uremia combined with myocardial damage group decreases gradually, but it is still the highest compared with the control group and the uremia group.Correlation analysis of nt-probnp level with LVEF and LVPWd shows that LVEF is negatively correlated with nt-probnp level.LVPWd was positively correlated with hs-crp level (P＜0.05).COX regression analysis showed that nt-probnp is an independent risk factor affecting the clinical prognosis of uremia patients.Studies have shown that [18], the level of nt-probnp is significantly positively correlated with systolic blood pressure, blood creatinine, dehydration and systemic edema. For patients with uremia combined with myocardial damage, it can effectively predict the patient's capacity load, thus assisting in the clinical determination of the patient's dehydration and effectively reducing the risk of death from cardiovascular diseases.The results show that nt-probnp is of great value in the early diagnosis of uremia complicated with myocardial damage.

In summary, TnI, hs-crp and nt-probnp levels have important clinical significance for the early diagnosis of uremia patients with myocardial damage. The detection method is simple, fast, objective, and convenient for dynamic observation and treatment. It is recommended to detect and intervene in the early clinical stage.