Relationship between sKL, BSP and HD abdominal aortic calcification and prognosis

Qin Xu, Xiao-Qin Cai, Chun-Hong Zhang, Zhi-Qiang Wei, Suo-Jian Zhang, Hao Ding, Juan Cao

Department of Nephrology, Taixing People's Hospital, Taixing, Jiangsu 225400, China

Keywords:End-stage renal disease Hemodialysis Soluble Klotho protein Sialic acid Abdominal aortic calcifciation Prognostic quality

ABSTRACT Objective: To investigate the relationship between the expression levels of sKL and BSP and the calcification and prognosis of abdominal aorta in patients with HD. Methods: 130 patients with HD admitted to our hospital between January 2015 and June 2017 were selected as the research subjects; all patients were treated with Fresenius hemodialysis machine for intervention treatment; the expression levels of sKL and BSP in the patients' blood were monitored, and 30 mmonths were followed up The extent of calcification of the abdominal aorta and the quality of the prognosis of the patients were evaluated and the relationship between the expression levels of sKL and BSP and the calcification and prognosis of the abdominal aorta were analyzed. Results: The levels of sKL and BSP in the blood of patients with different degrees of abdominal aortic calcification were significantly different, and the differences were statistically significant (P ＜0.05). Among the patients with mild or no calcification, the levels of sKL and BSP were the highest in the blood and those in the death group were the lowest. The sKL level was significantly lower than the survival group, and the BSP level was significantly higher than the survival group, and the differences were statistically significant (P ＜0.05); the survival rate of patients with high sKL expression was significantly better than that of patients with low sKL expression, and the survival rate of low BSP expression was significantly better High expression in BSP; high sKL and low BSP are independent protective factors affecting abdominal aortic calcification and prognostic quality in HD patients (P ＜0.05); combined use of sKL and BSP in predicting the prognostic quality of HD patients is sensitive and specific Both are greater than 90%, and AUC＞ 0.90. Conclusions: High sKL and low BSP in the blood of HD patients are independent protective factors affecting abdominal aortic calcification and prognostic quality. The combined application of sKL and BSP can effectively predict the prognostic quality value of patients.

1. Introduction

End-stage renal disease (ESRD) is a common chronic kidney disease in the clinic, and vascular calcification is a common and serious complication. At present, hemodialysis (HD) is often used to treat patients in the clinic [1]. Vascular calcification is the main cause of cardiovascular disease, and it will increase the mortality of patients with cardiovascular disease [2]. Serum soluble Klotho protein (s KL) is mainly derived from the extracellular domain of membrane-type Klotho protein. Membrane-type Klotho protein participates in a variety of biological responses and regulates calcium and phosphorus metabolism in renal tubules [3]. At present, many studies have shown that s KL is an important protective factor for vascular calcification, which is of great significance for improving the prognosis of dialysis patients, but its relationship with abdominal aortic calcification and prognosis in hemodialysis patients is not clear [4]. Bone sialic acid (BSP) is a key protein in bone-vascular axis metabolism. Studies have found that it plays an important role in vascular calcification in patients with uremia, but its mechanism of action is unclear [5]. This study took HD patients admitted to our hospital as the research object, observed the expression levels of sKL and BSP in vivo, and explored the relationship between changes in indicators and their abdominal aortic calcification and prognosis, in order to provide new ideas for vascular calcification treatment in HD patients.

2. Materials and methods

2.1 Entry criteria

(1) The patient's age is ≥18 years; (2) The duration of dialysis is＞ 3 months; (3) Normal mental health can cooperate with this study; (4) No antibiotics, hormones or immunosuppressive drugs have been taken within four weeks before enrollment; (5) No history of kidney transplantation; (6) The patient and his legal guardian were informed of the study and signed an informed consent.

2.2 Exclusion criteria

(1) history of surgery or trauma in the first half of the year; (2) severe diseases such as severe malabsorption and malignancy; (3) patients with acute infection; (4) primary autoimmune diseases; (5) entry Those who died within three months after the group; (6) Lost follow-up or volunteered to withdraw from the study.

2.3 General Information

The research plan and protocol were reviewed and approved by the ethics committee. 130 patients with HD who met the admission criteria and were admitted to our hospital from January 2015 to June 2017 were selected as the research subjects, including 53 males, age (47.43 ± 7.64 ), Dialysis age (30.52 ± 7.32) months, body mass index (21.74 ± 9.48) kg/m2, 32 cases of smoking history, 11 cases of diabetes, 13 cases of hypertension, 9 cases of cardiovascular disease.

2.4 Method

All patients in this group of patients were treated with Fresenius hemodialysis machine. Patients were treated with bicarbonate dialysate (ion concentration 1.5 mmol / L) during dialysis. The central vein semi-permanent catheter or autologous arteriovenous fistula As a blood route, each dialysis treatment was performed for 4 hours, each blood flow was 200-250 mL, and the dialysis treatment was performed three times a week.

The fasting venous blood of the patients was collected, the serum was collected by centrifugation, and the sKL and BSP levels in the patients' blood were detected by enzyme-linked immunosorbent assay, and the operation was strictly followed in accordance with the instructions of the kit. X-ray plain film examination was performed on all patients, and the examination sites included the 1st to 5th lumbar vertebrae, the 11th and 12th thoracic vertebrae, and the 1 to 2 sacral vertebrae. The patients' lumbar vertebrae were treated with semi-quantitative method to wait for calcification of our abdominal aorta. Scoring is based on the length of the patient's abdominal aortic wall plaque. 0 points: no calcification; 1 point: the calcification range is less than one-third of the arterial wall length; 2 points: the calcification range is one-third to one-third Arterial wall length of 2; 3 points: Arterial wall with calcification length greater than two thirds, and the patients' abdominal aortic calcification score (AAC) [6] was evaluated by two radiologists in an independent doubleblind method. The score is 0 to 24, of which 4 or less is no or mild calcification, 5 to 15 is moderate calcification, and 16 or more is severe calcification. All subjects were followed for 30 months to record new non-fatal CVD and patient deaths.

2.5 Statistical methods

In this group of studies, SPSS 20.0 was used for statistical analysis. The percentage and mean ± standard deviation were used to indicate the count and measurement data, and the chi-square and t test or variance test was used to indicate the difference between the count and measurement data. The multiple logistic regression model was used to analyze the indicators and The relationship between abdominal aortic calcification and prognosis, the Camille survival curve was used to analyze the prognosis quality of patients, and the ROC curve was used to analyze the application value of each index in assessing the prognosis quality of patients. P ＜0.05 considered the difference to be statistically significant.

3. Results

3.1 Detection results of blood sKL and BSP levels in patients with different degrees of abdominal aortic calcification

The results of this group of studies showed that there were significant differences in sKL and BSP levels in patients with different degrees of abdominal aortic calcification, and the differences were statistically significant (P ＜0.05). The patients with mild or no calcification had the highest levels of sKL in blood and BSP The lowest level is shown in Table 1.

Table 1 Results of blood sKL and BSP levels in patients with different degrees of abdominal aortic calcification

3.2 Results of blood sKL and BSP levels in patients with different prognostic quality

The results of this group of studies showed that the sKL level in the death group was significantly lower than that in the survival group, and the BSP level was significantly higher than the survival group, and the differences were statistically significant (P ＜0.05). In addition, the survival rate of patients with high sKL expression was significantly better than sKL. In patients with low expression, the survival rate of BSP low expression is significantly better than that of BSP high expression. See Table 2 and Figure 1 for details.

Table 2 Detection results of sKL and BSP levels in patients with different prognostic qualities

Figure 1 Camille survival curve

3.3 Relationship between sKL and BSP and abdominal aortic calcification and prognostic quality

The results of this group of studies show that high sKL levels are independent protective factors that affect abdominal aortic calcification and prognostic quality in HD patients (P ＜0.05), and high BSP levels are independent threats that affect patients' abdominal aortic calcification and prognostic quality Factors (P ＜0.05), see Table 3 for details.

Table 3 Relationship between sKL and BSP and abdominal aortic calcification and prognostic quality

3.4 The value of sKL and BSP in predicting the quality of patients' prognosis

The results of this group of studies show that the combined use of sKL and BSP in predicting the prognostic quality of HD patients has a sensitivity and specificity greater than 90%, and AUC＞ 0.90, which has high application value. See Table 4 and Figure 2 for details.

Table 4 Values of sKL and BSP in predicting the quality of patients' prognosis

Figure 2 ROC curve

4. Discussion

The anti-aging gene Klotho is mainly expressed in the brain choroid, kidney and reproductive organs, and is most abundantly expressed in renal tubular epithelial cells [7]. Klotho protein is expressed by the antiaging gene Klotho and can be divided into secreted Klotho protein and membrane-type Klotho protein. Secreted Klotho protein and a part of the protein secreted by the membrane-type Klotho protein form a soluble protein (sKL) [8]. Klotho protein in the blood mainly exists in the form of s KL, and participates in a variety of physiological functions, including antioxidant, anti-inflammatory, regulating energy metabolism and mineral metabolism [9]. Klotho gene expression in patients with kidney injury decreases, and sKL levels also decrease. Some studies have shown that a decrease in sKL levels will increase the incidence and severity of vascular calcification [10].

Vascular calcification is one of the major risk factors for cardiovascular disease, and studies have confirmed that vascular calcification and cardiovascular disease are closely related to abnormal calcium and phosphorus metabolism [11]. Fibroblast growth factor 23 (FGF23) is an important regulator in the production and secretion of vitamin D and phosphorus, which can reduce the reabsorption of phosphorus in raw urine, promote the excretion of phosphorus, and reduce the absorption rate of phosphorus in the small intestine [12].

Studies have shown that sKL can reduce phosphorus by activating FGF23, and it can also directly reduce phosphorus [13]. BSP is a type of bone metabolism marker. Its N-terminal glutamic acid plays a role in binding to hydroxyapatite, and participates in the formation of hydroxyapatite crystal nuclei, induces mineralization, increases calcium and phosphorus accumulation, and promotes Calcification [14]. BSP is an important marker of tissue calcification, and its expression can indicate the state of functional cells in tissues [15].

The results of this group of studies showed that there were significant differences in the levels of sKL and BSP in the blood of patients with different degrees of abdominal aortic calcification, with the highest level of sKL in the blood and the lowest level of BSP in the patients with mild or no calcification. The results of investigation on the quality of patients' prognosis showed that the sKL level in the death group was significantly lower than that in the survival group, and the BSP level was significantly higher than that in the survival group. In addition, the survival rate of patients with high sKL expression was significantly better than that of patients with low sKL expression, and the survival rate of low BSP expression was significant Better expression than BSP. The results of logistic regression analysis showed that high sKL levels were independent protective factors affecting abdominal aortic calcification and prognostic quality in HD patients, while high BSP levels were independent threatening factors that affected patients' abdominal aortic calcification and prognostic quality. The analysis of sKL and BSP levels for predicting the prognosis of patients shows that the sensitivity and specificity of sKL and BSP in predicting the prognosis quality of HD patients are greater than 90%, and AUC＞ 0.90, which has high application value. According to the analysis, sKL protein can effectively inhibit the synthesis of active vitamin D and PTH in the body, and can effectively directly affect renal tubular epithelial cells in the body to accelerate urinary phosphorus excretion, and may be involved in regulating vascular calcification in the body, while abnormally elevated BSP levels may be involved The patient's condition further deteriorated, and the results suggest that in the clinic, if patients have elevated sKL and BSP in the blood, they should be paid attention to, and timely intervention should be made to correct the abnormal state of the patient's body as much as possible and improve the quality of patients' prognosis.

In summary, high sKL and low BSP in blood of HD patients are independent protective factors affecting abdominal aortic calcification and prognostic quality, and the combined application of sKL and BSP can effectively predict the prognostic quality value of patients. However, this study is a single-center small-sample study, which needs to be further expanded and further investigated.