|Year : 2018 | Volume
| Issue : 2 | Page : 402-406
Correlation between serum triiodothyronine level and inflammation in hemodialysis patients
Mostafa M Elnagar1, Alaa E Abdel-Salam Dawood1, Eslam M Abdelwahab Elshewy2
1 Department of Internal Medicine, Faulty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Internal Medicine, ElSenbelaween Hospital, Dakhlia Governorate, Egypt
|Date of Submission||14-Mar-2016|
|Date of Acceptance||26-Jun-2016|
|Date of Web Publication||27-Aug-2018|
Eslam M Abdelwahab Elshewy
Source of Support: None, Conflict of Interest: None
The aim of this work was to study the correlation between serum free triiodothyronine (FT3) level and inflammation in hemodialysis (HD) patients.
End-stage renal disease (ESRD) is associated with a markedly increased mortality risk, with cardiovascular diseases being the most common cause of death. FT3 is a marker of comorbidity in ESRD and in many acute and chronic diseases.
Patients and methods
This case–control study included 30 patients with ESRD on maintenance HD (17 men and 13 women) (mean age 43.93 ± 12.12 years), 20 patients with chronic kidney disease not on HD (12 male and eight female) (mean age 42.4 ± 12.42 years), and 20 healthy controls (12 male and eight female) (mean age 37.25 ± 10.52). Serum FT3 and thyroid-stimulating hormone concentrations were determined. C-reactive protein (CRP) was used as a marker of inflammation. Demographic data and laboratory values were evaluated.
Our results showed a significantly lower serum FT3 level in the HD group compared with the chronic kidney disease and control groups (P < 0.001). Moreover, it showed nonsignificant differences in the serum thyroid-stimulating hormone levels between all groups (P = 0.765). In the HD group, there was a significant negative correlation between serum FT3 and CRP level (ρ=−0.83; P= 0.001), between serum CRP and albumin levels (ρ=−0.37; P= 0.004), and between serum FT3 level and number of dialysis years of patients (ρ=−0.455; P= 0.012). In contrast, a positive correlation was noticed between serum CRP levels and number of dialysis years of patients (ρ=0.371; P= 0.044).
The results of this study indicate a significant inverse correlation between CRP and plasma T3 circulating levels in patients undergoing HD. This investigation suggested that inflammation might be involved in the low T3 syndrome in HD patients. Thus, we suggest that FT3 levels can be used as a marker for inflammation in ESRD patients.
Keywords: hemodialysis, inflammation, triiodothyronine
|How to cite this article:|
Elnagar MM, Abdel-Salam Dawood AE, Abdelwahab Elshewy EM. Correlation between serum triiodothyronine level and inflammation in hemodialysis patients. Menoufia Med J 2018;31:402-6
|How to cite this URL:|
Elnagar MM, Abdel-Salam Dawood AE, Abdelwahab Elshewy EM. Correlation between serum triiodothyronine level and inflammation in hemodialysis patients. Menoufia Med J [serial online] 2018 [cited 2018 Nov 16];31:402-6. Available from: http://www.mmj.eg.net/text.asp?2018/31/2/402/239722
| Introduction|| |
End-stage renal disease (ESRD) may affect thyroid functions in various ways attributed to the low blood hormone level; it affects the peripheral hormone metabolism reducing the binding to transport proteins, decreases the tissue hormone quantity, and induces the uptake of iodine by the thyroid gland . ESRD is associated with a markedly increased mortality risk, with cardiovascular diseases being the most common cause of death . Low T3 is a significant independent risk factor for all-cause mortality in hemodialysis (HD) patients, and its impact on mortality may be attributed, in part, to malnutrition and cardiac dysfunction .
Some authors have recommended measurement of T3 levels to assess the relationship between thyroid dysfunction and risk for mortality in uremic patients . HD is associated with alterations in the concentration of circulating thyroid hormones, usually a reduction in serum total and free triiodothyronine (FT3) concentrations . Chronic kidney disease (CKD) is a recognized cause of nonthyroidal illness . Derangement of thyroid function in nonthyroidal illness is currently presumed as an acute-phase response produced by activation of cytokine network . Cytokines are also suggested to decrease the activity of type I deiodinase and to decrease the binding capacity of T3 nuclear receptors . An inflammatory process in ESRD is associated with uremia, an increased incidence of infections, and elevated levels of proinflammatory cytokines . The significance of C-reactive protein (CRP) and inflammation has increased in ESRD population, as elevated CRP levels have been identified as a risk factor for cardiovascular disease in ESRD . There is a relationship between plasma levels of T3 and various markers of inflammation, nutrition, and endothelial activation in patients with CKD . There is a lack of data about the relationship between plasma FT3 levels, malnutrition, and inflammation in HD patients. Thus, the aim of our study was to investigate the correlation between plasma FT3 levels and inflammation (using CRP as a marker of inflammation) in HD patients.
| Patients and Methods|| |
The study was approved from the ethical committee of faculty of medicine menoufia university and the patients gave an informed consents. This case–control study was conducted on a total of 50 patients. They were divided into two main groups: 30 patients with ESRD on maintenance HD (17 men and 13 women) (mean age 43.93 ± 12.12 years), and 20 patients with CKD who were not on HD (12 and eight female) (mean age 42.4 ± 12.42 years). In addition, 20 healthy controls (12 male and eight female) (mean age 37.25 ± 10.52 years) were selected to participate in the study. The difference between groups was nonsignificant as regards age and sex (P = 0.97 and 0.14, respectively). Patients' clinical and demographic characteristics and routine laboratory parameters were recorded at the initiation of the study, to exclude any significant metabolic disorder that could alter thyroid hormone metabolism-associated comorbidity, particularly diabetes mellitus (DM) and hypertension (HTN). All HD patients were on 4 h bicarbonate dialysis, three times a week. Different causes of primary kidney disease in CKD patients were recorded (DM, HTN, and others). Informed consent was obtained from all study participants. The criteria of inclusion included being on dialysis for more than 6 months for the HD group, age 16 years or older, and diagnosis of CKD for the CKD group. We excluded patients diagnosed with primary thyroid disorders (hypothyroidism and hyperthyroidism), associated current illnesses (infectious diseases, associated malignancy, or any other diseases requiring hospitalization) or taking drugs that may affect the plasma concentration of thyroid hormones (i.e., amiodarone, beta blocker, and lithium).
Plasma levels of FT3 and thyroid-stimulating hormone (TSH) were measured with a commercially available sensitive immunometric assay kit (Bio-Maria Company, Indoor Biotechnologies, Inc, 700 Harris Street, Charlottesville, VA 22903, USA). The reference values were 0.4–4 μIU/ml for TSH levels, and 3–7.8 pmol/l for FT3 levels. We selected CRP marker (Human Company) as the inflammation marker in patients with reference values negative up to 15 IU/ml.
Statistical analysis was carried out using statistical package for social science, version 17 program on Windows 7 (SPSS Inc., Chicago, Illinois, USA). Qualitative data were represented in the form of number and percentage, whereas quantitative data were represented in the form of mean ± SD. The Kolmogorov–Smirnov test was used to test normality of quantitative data. The χ2, one-way analysis of variance, and Kruskal–Wallis tests were used to compare groups. Spearman's rank correlation test was used to study correlation between parameters. Results were considered significant if P value was less than or equal to 0.05.
| Results|| |
The HD group consisted of 30 patients (17 men and 13 women) with a mean age of 43.93 ± 12.12 years, and the CKD group included 20 patients (12 and eight female) with a mean age of 42.4 ± 12.42 years. A total of 20 healthy individuals were included as the control group (12 male and eight female) with a mean age of 37.25 ± 10.52 years. Causes of primary kidney diseases in the second group (the CKD group) were DM in eight (40%), HTN in five (25%), glomerulonephritis in four (20%), autosomal dominant polycystic kidney disease (ADPKD) in two (10%), and unknown in one (5%). Demographic and clinical data of participants in each group are shown in [Table 1] and [Table 2].
There were significantly higher serum levels of CRP in the HD group compared with the CKD and control groups (P < 0.001). Serum FT3 levels were significantly reduced in the HD group compared with the CKD and control groups (P < 0.001). Moreover, it showed nonsignificant differences in serum TSH levels between groups (P = 0.765) [Figure 1].
|Figure 1: Serum free T3 and TSH levels comparison in study groups. CKD, chronic kidney disease; TSH, thyroid-stimulating hormone; T3, triiodothyronine.|
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[Table 3] and [Figure 2] show that, in the HD group, there was a significant negative correlation between serum FT3 and CRP level (ρ=−0.83; P= 0.001), between serum CRP and albumin levels (ρ=−0.37; P= 0.004), and between serum FT3 level and number of dialysis years of patients (ρ=−0.455; P= 0.012). However, a positive correlation was noticed between serum CRP levels and number of dialysis years of patients (ρ=0.371; P= 0.044).
|Table 3 Significant correlations between biochemical and clinical parameter in the hemodialysis group|
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|Figure 2: Correlation between serum free T3 and CRP levels in the hemodialysis group. CRP, C-reactive protein; T3, triiodothyronine.|
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| Discussion|| |
The thyroid hormone has numerous effects on the kidney, playing an important role in renal development and growth as well as in sodium and water homeostasis. renal plasma flow and glomerular filtration rate are also influenced by thyroid hormone, resulting in reductions in renal plasma flow and glomerular filtration rate and an increase in serum creatinine concentrations . Alterations in thyroid hormone metabolism have been reported in patients with a variety of nonthyroidal illnesses . Derangement of thyroid function in nonthyroidal illness is currently presumed as an acute-phase response produced by activation of cytokine network . ESRD is the irreversible deterioration of renal function, which results in the impairment of excretory, metabolic, and endocrine functions leading to the development of the clinical syndrome of uremia . Majeed and colleagues measured the levels of serum urea, creatinine, total T4, total T3, FT4, FT3, and TSH in the serum of 80 patients with varying grades of chronic renal failure and 40 healthy individuals. They concluded that uremia is accompanied with endocrine disorders, due to impaired degradation of hormones .
Uremic patients demonstrated complex thyroid dysfunction characterized by markedly depressed levels of T3 and lower (but still normal) T4 with a normal TSH . HD is associated with alterations in the concentration of circulating thyroid hormones, usually a reduction in serum total and FT3 concentrations . Increased CRP is a strong risk factor for mortality within 1 year in patients with ESRD. Furthermore, elevated CRP levels have been identified as a risk factor for cardiovascular disease in ESRD. It has become evident that inflammation plays an important role in the pathogenesis of atherosclerotic complications . Cytokines are also suggested to decrease the activity of type I deiodinase and to decrease the binding capacity of T3 nuclear receptors . As inflammation influences thyroid function, low plasma T3 in ESRD could be an expression of the inflammatory state of these patients . A relationship between T3 level and mortality has been documented in patients on HD . Malyszko et al. have recommended measurement of T3 levels to assess the relationship between thyroid dysfunction and risk for mortality in uremic patients.
In a few articles, correlation between T3 and high sensitivity C-reactive protein (hsCRP) in HD and peritoneal dialysis (PD) patients simultaneously has been evaluated so far, but this area still remains unclear. Therefore, we investigated the relationships between serum triiodothyronine level and inflammation in HD patients.
Our study showed that a significantly higher serum level of CRP were detected in the HD and the CKD group compared with the control group (P < 0.001). Zeraati et al. showed no statistically significant differences between the three groups (the HD, PD, and control groups) with respect to HSCRP. Borazan et al. reported a wide range of CRP levels in patients undergoing dialysis.
In our study, serum FT3 levels were significantly reduced in the HD group compared with the CKD and control groups (P < 0.001). Lim  showed that HD patients would have a higher probability of reduced T3 compared with PD patients. Zeraati et al. showed that circulating levels of plasma T3 in the dialysis patients were significantly lower than those in the age and sex matched controls. Chopra et al. showed no significant differences in the levels of T3 according to the type of dialysis.
In our study, in the HD group, a significant negative correlation was found between serum FT3 and CRP level (ρ=−0.83; P= 0.001), between serum CRP and albumin levels (ρ=−0.37; P= 0.004), and between serum FT3 level and number of dialysis years of patients (ρ=−0.455; P= 0.012). However, a positive correlation was noticed between serum CRP levels and number of dialysis years of patients (ρ=0.371; P= 0.044). Abozenah et al. showed a relatively weak correlation between CRP concentration and FT3. Enia et al. showed that inflammation is linked to the low T3 syndrome in CKD patients. Zoccali et al. showed that FT3 is associated with markers of inflammation and endothelial activation in stable HD patients. In another study, Carrero et al. showed that T3 levels were associated with increased inflammation (higher hsCRP and IL-6) and lower concentrations of both albumin and insulin-like growth factor 1.
Zeraati and colleagues investigated the relationship between HSCRP and T3 in patients undergoing PD and HD. They suggested that inflammation might be involved in the low T3 syndrome in HD patients as there was an inverse correlation between T3 and HSCRP, but they did not find a significant correlation between T3 and HSCRP levels in patients on PD .
In agreement with previous evidence, our HD patients are characterized by a significant inverse correlation between T3 and CRP in the present study population.
| Conclusions and Recommendations|| |
Our study revealed a significant inverse correlation between CRP and plasma FT3 levels in patients undergoing HD. Thus, we suggest that FT3 levels can be used as a marker of inflammation in ESRD patients. However, it is still unclear whether or not the low T3 state contributes to the development and progression of inflammatory state in PD patients. Hence, further studies are required to confirm our results.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]