Investigation of plasma Homocysteine concentrations and their relationship with some clinical and laboratory characteristics of patients treated with maintenance hemodialysis

Nội dung text: Investigation of plasma Homocysteine concentrations and their relationship with some clinical and laboratory characteristics of patients treated with maintenance hemodialysis

1. Journal OF MILITARY PHARMACO - MEDICINE N06 - 2021 INVESTIGATION OF PLASMA HOMOCYSTEINE CONCENTRATIONS AND THEIR RELATIONSHIP WITH SOME CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS TREATED WITH MAINTENANCE HEMODIALYSIS Nguyen Van Tuyen1,2, Bui My Hanh3, Le Viet Thang4 SUMMARY Objectives: To investigate plasma homocysteine (Hcy) concentrations and their relationship with some clinical and laboratory characteristics of patients treated with maintenance hemodialysis (MHD). Subjects and methods: A cross-sectional descriptive study, compared with control groups on 199 subjects, including 111 patients diagnosed with end-stage chronic kidney disease treated with MHD and 88 healthy people of the same age and sex. The plasma Hcy levels were quantified by turbidimetric immunoassay in all subjects. Results: The mean plasma Hcy concentration of the patients was 38.49 ± 11.26 26 µmol/L, higher than that of the control group, p < 0.001. There were 71.2% patients with increased concentration compared to the control group. The mean plasma Hcy concentration in male patients; duration of hemodialysis ≥ 5 years; loss of residual renal function; diabetes mellitus; smoking was higher than the patient group without the above characteristics, p < 0.05. Hcy concentration was negatively correlated with HDL-C concentration, r = -0,301, p < 0.01. Conclusion: Increased plasma Hcy levels are common and associated with some MHD patients’ clinical and laboratory characteristics. * Keywords: Maintenance hemodialysis; Plasma homocysteine; Duration of hemodialysis; Residual renal function. INTRODUCTION hypertension, diabetes, obesity, smoking, Atherosclerosis is the thickening of the inflammation... The consequences of artery walls as a result of the atherosclerosis process are the hardening accumulation of fats such as cholesterol of the arteries, in which arterial walls and other substances including triglycerides become thickened and hardened by plaque, and calcium. Atherosclerosis affects the causing loss of elasticity of medium and arterial lining, forming a chronic inflammatory large arteries. Atherosclerotic plaques can response in the arterial walls [2, 3]. restrict blood flow in the artery, and if the Atherosclerosis has many risk factors plaque ruptures, the flow can partially or such as lipid metabolism disorders, completely obstruct the blood vessels [3, 4]. 1Vietnam Military Medical University 2Duc Giang General Hospital, Hanoi 3Hanoi Medical University 4Military Hospital 103, Vietnam Military Medical University Corresponding author: Nguyen Van Tuyen (tuyenbvdkdg@gmail.com) Date received: 20/5/2021 Date accepted: 04/6/2021 175
2. Journal OF MILITARY PHARMACO - MEDICINE N06 - 2021 In recent years, Hcy has emerged as a * Exclusion criteria: non-traditional factor involved in the - Patients are suffering from acute process of atherosclerosis. For all patients illnesses such as viral fever, pneumonia, of end-stage renal disease on maintenance bronchitis... hemodialysis (MHD), Hcy is often elevated - Suspected surgical disease. in the blood, which is associated with - Not enough research contents arterial stiffness and related factors. In Vietnam, there have not been many 2. Methods studies on Hcy concentrations in MHD * Study design: Cross-sectional study patients, for the above reasons, we combined with description, comparison carried out the study: To investigate with control groups. plasma Hcy concentrations and their - Take personal and family history. relationship with some clinical and - Ask the patient and examine the paraclinical characteristics of MHD patient to detect clinical signs and symptoms. patients. - 24-hour urine measurement, assess SUBJECTS AND METHODS the status of urine left or lost. 1. Subjects - Take venous blood to test blood count, blood biochemistry. The study subjects included 199 people - Quantification of plasma Hcy (Hcy) divided into 2 groups: concentration: Take venipuncture of - The disease group: 111 patients with fasting subjects. Anticoagulation followed end-stage chronic kidney disease, treated by plasma separation. Quantification of with MHD. plasma Hcy by enzyme colorimetric - The control group: 88 healthy people method. Unit: µmol/L. Determine increase of the same age and sex. or reduction of plasma Hcy concentrations * Selection criteria: basing on values of healthy controls. The - Patients with end-stage chronic kidney patient group values that were considered disease treated with MHD. normal were within X ± 2SD of the control - Duration of hemodialysis ≥ 3 months. group. When the patient has a Hcy - Dose of hemodialysis, treatment of concentration value < X -2SD value, the anemia and hypertension according to the concentration is determined to decrease, guidance of the Ministry of Health, and if the value is > X +2SD, the individualized for each patient. concentration is determined to increase. - Do not take drugs that affect Hcy * Data processing: Using SPSS 22.0 levels. software. Figures were drawn automatically - Agree to participate in the study on the computer. 176
3. Journal OF MILITARY PHARMACO - MEDICINE N06 - 2021 RESULTS AND DISCUSSION The mean age was 55.22 ± 13.74 years, male accounted for 49.5%, the median duration of hemodialysis was 30 months (13 - 74). Table 1: Comparison of plasma Hcy concentrations in the disease and the control groups. Index Control group (n = 88) Patient group (n = 111) p Mean ( X ± SD), (µmol/L) 17.23 ± 6.16 38.49 ± 11.26 Min 4.18 19.47 < 0.001 Max 36.6 61.05 The mean value of plasma Hcy concentration in the patient group was higher than that in the control group, p < 0.001. The minimum and maximum plasma Hcy values were also higher in the disease group than in the control group. Figure 1: The rate of the increased plasma Hcy concentration (n = 111). Increased plasma Hcy concentration and especially, the Hcy concentration was was common, accounting for 71.2% of reduced in GFR patients. In patients with patients with MHD. Compared to the CKD with and without MHD, Chen C.H. et research results of domestic and foreign al. (2017) [6] also confirmed that the authors, we found that there were many concentration of Hcy in the group of similarities. Diem Thi Van's study (2016) MHD patients was higher than in the [4] on 112 patients with MHD, compared group with CKD stage 2 and 3, p < 0.01. to 56 healthy people, also showed that To understand why Hcy is higher in CKD the Hcy concentration of the disease patients than in normal people, it is first group was higher than that of the control necessary to understand the metabolism group, p < 0.001. In patients with chronic of Hcy in the human body. Hcy is a kidney disease (CKD) from stage 1 to 5, non-essential, sulfur-containing, protein-free Chaitanya V. et al. (2018) [5] also showed amino acid. It is synthesized by metabolizing that Hcy concentration in the disease the essential amino acid methionine, group was higher than in the control group derived from the diet, and synthesized 177
4. Journal OF MILITARY PHARMACO - MEDICINE N06 - 2021 only in humans. In patients with end-stage deficiency) and/or vitamin deficiency (B6, renal failure, there are many factors B12 or folic acid). Folic acid's ability to involved in the increasing blood Hcy. reduce serum Hcy is due to the Possible causes include decreased stimulation of Hcy remethylation in renal clearance (particularly altered methionine. These observations suggest tubular function), altered Hcy metabolism that dialysis patients who are resistant to (increased peroxidation), genetic abnormalities folic acid therapy are also responsible for undiagnosed (cystathionine-β- synthetase the elevation of Hcy. Table 2: Relationship of plasma Hcy concentration with age and sex. Ratio of increase Index Mean ( ± SD), (µmol/L) X (n, %) < 40 (n = 15) 33.61 ± 11.27 8 (53.3) 40 - < 60 (n = 55) 38.72 ± 10.19 40 (72.7) Age ≥ 60 (n = 41) 39.96 ± 12.35 31 (75.6) pANOVA > 0.05 > 0.05 Male (n = 55) 40.73 ± 10.81 43 (78.2) Sex Female (n = 56) 36.29 ± 11.35 36 (64.3) p 0.05 There was no relationship between plasma Hcy concentrations and age groups. However, male patients had a significantly higher mean Hcy concentration than female patients (p < 0.05). Elevated plasma Hcy levels are common in many different diseases, including cardiovascular and renal diseases [7]. Hcy has been recognized as an independent risk factor for cardiovascular diseases. It has been estimated that a 2.5 µM increase in plasma, Hcy concentration is associated with a 10% increased risk of cardiovascular disease [7]. It is possible that the male gender is a cardiovascular risk factor, and therefore, Hcy concentration is higher than female. Table 3: Relationship between hemodialysis time and residual kidney function. Index Ratio of increase Mean ( X ± SD), (µmol/L) (n, %) < 5 years (n = 75) 36.06 ± 10.45 50 (66.7) Duration of hemodialysis ≥ 5 years (n = 36) 43.55 ± 11.33 29 (80.6) p 0.05 No (n = 88) 39.75 ± 11.02 67 (76.1) Yes (n = 23) 33.66 ± 11.1 12 (52.2) Residual kidney function OR, p p < 0.05 < 0.05 OR = 2.925 The group of patients with hemodialysis duration ≥ 5 years had a higher mean plasma Hcy concentration than the group of patients with a duration of hemodialysi < 5 years 178
5. Journal OF MILITARY PHARMACO - MEDICINE N06 - 2021 (p < 0.01). The patients without residual renal function had a 2.925 times higher rate of increased Hcy concentration than the patients with residual renal function (p < 0.05). Figure 2: Correlation of plasma Hcy concentration with hemodialysis time in the disease group (n = 111). The plasma Hcy concentration had a positive correlation with hemodialysis duration, r = 0.287 (p < 0.005). Prolonged time of hemodialysis and loss of residual renal function are two characteristics that always go together. In patients on long-term hemodialysis, especially after 5 years, systemic disorders affected by dialysis are more likely to occur, including inflammation, malnutrition, and atherosclerosis. Furthermore, cardiovascular events are more likely to occur in patients with prolonged hemodialysis and loss of residual renal function [8]. The increasing concentration of Hcy directly affects the process of atherosclerosis, which forms a vicious cycle. That makes the disease progress more seriously, cardiovascular events such as stroke, myocardial infarction or aortic dissection, and peripheral artery disease more severe. Table 4: The association between plasma Hcy concentration and diabetes and smoking. Index Mean ( X ± SD), (µmol/L) Ratio of increase (n, %) Yes (n = 21) 45.5 ± 10.33 18 (85.7) No (n = 90) 36.85 ± 10.88 61 (67.8) Diabetic mellitus p > 0.05 OR, p < 0.005 OR = 2.852 Yes (n = 21) 43.88 ± 9.68 18 (85.7) No (n = 90) 37.23 ± 11.28 61 (67.8) Smoke p > 0.05 OR, p < 0.05 OR = 2.852 179
6. Journal OF MILITARY PHARMACO - MEDICINE N06 - 2021 The mean value of Hcy concentration diabetic retinopathy and diabetic nephropathy. in the patients with diabetes or smoking Long-term metformin use increases the was higher than the group without the risk of vitamin B12 and folate deficiencies, above features, p < 0.05. Diabetic mellitus thereby affecting Hcy metabolism and (DM) and smoking are two risk factors for contributing to the progression of atherosclerosis. Hcy is a sulfur-containing diabetic retinopathy as well as diabetic amino acid formed by the demethylation nephropathy. Wang H. et al. [3] of methionine. Plasma Hcy levels are investigated the relationship of total elevated in DM patients, especially plasma Hcy with albuminuria and its those in type 2 DM, as well as in clinical applicability in predicting renal insulin-resistant prediabetes [9]. Changes function impairment in type 2 DM patients. in plasma Hcy concentrations in DM Study results showed that Hcy levels patients are often related to vitamin B were significantly increased in patients level and vitamin absorption. Vitamin B is with proteinuria and microalbuminuria. an important factor in Hcy metabolism. Elevated plasma concentrations of Hcy Elevated levels of Hcy and low levels may be due to the impaired Hcy of folic acid have been observed in clearance in patients with decreased DM patients, especially in patients with glomerular filtration rate (GFR). Figure 3: Correlation between plasma Hcy level and HDL-C in the disease group (n = 111). An inverse, moderate correlation clinical epidemiological study of 4,660 between Hcy concentration and HDL-C Chinese people, p < 0.001. Wang Y. et al. was detected in the study, r = -0,301, p < [10] evaluated the association between 0.01. Momin M. et al. [146] reported an Hcy levels and apoA-I in normal healthy association between increased Hcy, subjects. The study results showed that which was independently associated with plasma Hcy concentration was negatively lower HDL-C and higher triglycerides, in a correlated with HDL-C and apoA-I levels. 180
7. Journal OF MILITARY PHARMACO - MEDICINE N06 - 2021 Thus, the studies found an inverse vitamin B12 concentrations in patients with correlation between Hcy and HDL-C in regular hemodialysis. Journal of Practical both normal people and patients with MHD. Medicine 2016; 12(1029):71-74. In the study of Wang Y. et al. [10], plasma 2. Kobiyama K., Ley K. Atherosclerosis. Hcy concentration was negatively correlated Circ Res 2018; 123(10):1118-1120. with HDL-C and apoAI concentrations in 3. Taleb S. Inflammation in atherosclerosis. normal healthy subjects, and plasma Hcy Arch Cardiovasc Dis 2016; 109(12):708-715. concentration was an independent factor 4. Wang H., Cui K., Xu K., et al. affecting apoA-I concentration. Therefore, Association between plasma Hcy and it can be suggested that increased progression of early nephropathy in type 2 Hcy is associated with low plasma diabetic patients. Int J Clin Exp Med 2015; concentrations of apoA-I and HDL-C in 8(7):11174-11180. eCollection. healthy subjects. That inhibition of apoA-I 5. Chaitanya V., Devi N.H, Suchitra M.M, synthesis is a further mechanism by et al. osteopontin, cardiovascular risk factors which Hcy may be associated with the and carotid intima-media thickness in chronic kidney disease. Indian J Nephrol 2018; development of atherosclerosis in patients 28(5):358-364. with elevated Hcy. 6. Chen C.H, Yeh E.L, Chen C.C, et al. CONCLUSION vitamin b-6, independent of Hcy, is a Surveying plasma Hcy levels of 111 significant factor in relation to inflammatory patients with end-stage chronic kidney responses for chronic kidney disease disease treated with MHD, compared with and hemodialysis patients. Biomed Res Int 2017; 7367831. eCollection. 88 healthy people, we have the following comments: 7. Škovierová H., Vidomanová E., Mahmood S., et al. the molecular and cellular - The mean plasma Hcy concentration effect of Hcy metabolism imbalance on human in the hemodialysis patients was 38.49 ± health. Int J Mol Sci 2016; 17(10):1733. 11.26 µmol/L, significantly higher than the eCollection. control group, p < 0.001. The rate of the increasing plasma Hcy concentration was 8. Mathew A.T, Fishbane S., Obi Y., et al. 71.2%. Preservation of residual kidney function in hemodialysis patients: reviving an old - Male patient, hemodialysis time 5 ≥ concept. Kidney Int 2016; 90(2):262-271. years, loss of residual renal function, diabetes mellitus, smoking has a higher 9. Lei X., Zeng G., Zhang Y., et al. mean plasma Hcy concentration than Association between Hcy level and the risk patients without the above characteristics, of diabetic etinopathy: A systematic review p < 0.05. Hcy concentration was negatively and meta-analysis. Diabetol Metab Syndr correlated with HDL-C concentration, 2018; 10:61. eCollection. r = -0,301, p < 0.01. 10. Wang Y., Liu J., Jiang Y., et al. HyperHcymia is associated with decreased REFERENCES apolipoprotein AI levels in normal healthy 1. Diem Thi Van, Hoang Trung Vinh. people. BMC Cardiovasc Disord 2016; 16:10. Investigation of plasma Hcy, forlate and eCollection. 181