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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2018  |  Volume : 29  |  Issue : 6  |  Page : 1274-1279
Effect of thyroid function status in hemodialysis patients on erythropoietin resistance and interdialytic weight gain


1 College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
2 Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
3 Department of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

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Date of Submission22-Oct-2018
Date of Acceptance22-Oct-2018
Date of Web Publication27-Dec-2018
 

   Abstract 

Thyroid function abnormalities are common in hemodialysis (HD) patients. Here, we investigated their frequency and impact on intradialytic hemodynamics and erythropoietin resistance index (ERI). Demographic and laboratory data including thyroid-stimulating hormone (TSH), interdialytic weight gain, and intradialytic blood pressure (BP) changes were measured, and ERI was calculated. The prevalence and causes of abnormities in TSH and free thyroxine (FT4) and their effects on ERI and intradialytic hemodynamics were then assessed. One hundred and thirty patients (mean age, 57.1 ± 19.2 years; 66.4% diabetic, 86.7% hypertensive) were enrolled. Among them, 16.7% had hypothyroidism, 2.3% had hyperthyroidism, and 10.9% had subclinical hypothyroidism. TSH level was significantly associated with higher BP (P <0.05), lower albumin (3.6 ± 4.4 and 2.6 ± 1.8, respectively; P = 0.05), lower dialysis hours (3.9 ± 5.3 and 2.6 ± 1.8, respectively), and lower ERI (3.7 ± 4.4 and 2.4 ± 1.9, respectively; P = 0.05). FT4 was significantly associated with higher interdialytic weight gain (13.4 ± 4.3 and 11.8 ± 2.2 pmol/L, respectively; P = 0.009) and higher pre-HD diastolic BP (13.2 ± 4.0 and 12.0 ± 2.9 pmol/L, respectively; P = 0.05). A negative correlation was seen between TSH level and urea reduction ratio (r = 0.29, P = 0.002), serum albumin (r = 0.304, P = 0.001), hemoglobin level (r = 0.26, P = 0.005), and ERI (r = 0.2, P = 0.002). A higher TSH level was associated with hypertension, lower albumin level, fewer dialysis hours, and increased resistance to erythropoietin. TSH level was negatively correlated with dialytic adequacy, serum albumin level, hemoglobin level, and ERI.

How to cite this article:
Bin Saleh FS, Naji MN, Eltayeb AA, Hejaili FF, Al Sayyari AA. Effect of thyroid function status in hemodialysis patients on erythropoietin resistance and interdialytic weight gain. Saudi J Kidney Dis Transpl 2018;29:1274-9

How to cite this URL:
Bin Saleh FS, Naji MN, Eltayeb AA, Hejaili FF, Al Sayyari AA. Effect of thyroid function status in hemodialysis patients on erythropoietin resistance and interdialytic weight gain. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Jan 17];29:1274-9. Available from: http://www.sjkdt.org/text.asp?2018/29/6/1274/248310

   Introduction Top


End-stage renal disease (ESRD) affects thyroid function in multiple ways including lowering thyroid hormone level, increasing peripheral hormone metabolism, reducing the binding of the hormones to transport proteins, and inducing iodine uptake by the thyroid gland.[1],[2] The prevalence of thyroid abnormalities in hemodialysis (HD) patients is often underestimated because the insidious onset of hypothyroidism and its symptoms being similar to those of uremia and anemia associated with renal failure.[3],[4],[5] Treating anemia in HD patients with erythropoietin (EPO) can mask some clinical features of hypothyroi-dism.[6] When glomerular filtration rate (GFR) is reduced to <30 mL/min, thyroid sick syndrome becomes evident.[7] In addition, the peripheral denomination of thyroxine (T4) to triiodothyronine (T3) is impaired.[8] This manifests as a decrease in T3 more than that of T4 in progressive renal failure.[9] The reduction in plasma levels of FT3 in ESRD is associated with decreased conversion of T4 to T3 in the peripheral tissues.[10] Thyroid hormone concentrations could be affected by changes in the binding capacity of serum proteins.[11],[12] The abnormal serum constituents in uremia are thought to displace thyroid hormone from its protein-binding sites.[13]

Once patients are started on dialysis, thyroid functions are not normally routinely checked.[6]

Here, we assessed the factors affecting thyroid status in HD patients as well its relationship with EPO resistance, interdialytic weight gain, and dialysis adequacy.


   Methods Top


This cross-sectional cohort study included all adult patients dialyzing in the morning and afternoon shifts at King Abdulaziz Medical City, Riyadh, who were on HD for ≥3 months. The study was performed in October 2017. Patients with concurrent acute illnesses were excluded.

The following parameters were recorded: thyroid function tests [FT4, thyroid-stimulating hormone (TSH)], interdialytic weight gain, intradialytic blood pressure (BP) changes, and the EPO resistance index (ERI) = (average weekly EPO dose/weight)/hemoglobin (Hgb). Subclinical hypothyroidism was diagnosed in the presence of a raised TSH level with normal FT4 levels.

The Statistical Package for the Social Sciences version 21.0 (SPSS Inc., Chicago, IL, USA) was used for the statistical analysis. Descriptive statistics were generated, and the correlations between free T4 and TSH with continuous variables were calculated using Pearson’s correlation coefficient. The independent sample t-test was used to assess whether there were significant differences in TSH and T4 values below and above the 50th percentile of continuous variables [e.g., urea reduction ratio (URR), serum albumin, Hgb, ERI, and age] or of dichotomous group variables [e.g., sex, mode of dialysis, presence or absence of diabetes or hypertension, vascular access type, intradia-lytic hypotensive episodes, and type of EPO-stimulating agents (ESA)] used. Stepwise multiple regression analysis was used to evaluate the independent effect of parameters on ERI and interdialytic weight gain.

The study was approved by the Institutional Review Board of King Saud Bin Abdulaziz University for Health Sciences.


   Results Top


A total of 130 patients were enrolled (mean age, 57.1 ± 19.2; 46.7% males, 77.3% on HD, 22.7% on hemodiafiltration). Of them, 44.1% were dialyzing using arteriovenous fistula and 54.8% through a permcath, 17.1% had a previous transplant, 66.4% were diabetic, and 86.7% were hypertensive. Intradialytic hypotension requiring fluid resuscitation occurred in 17.1% of patients. The ESA used was darbepoetin in 43.4% and EPO in 56.6%. The mean Kt/V was 1.6 ± 0.48; albumin, 36.4 ± 3.92 g/L; cholesterol, 3.8 ± 0.92 mmol/L; Hgb, 114.8 ± 16.1 g/L; ferritin, 468.8 ± 355.4 pmol/L; pre-HD systolic BP (SBP), 143.8 ± 27.7 mm Hg; pre-HD diastolic BP (DBP), 67.3 ± 18.3 mm Hg; post-HD SBP, 139.4 ± 22.4 mm Hg; post-HD DBP, 66.6 ± 14.9 mm Hg; and interdialytic weight gain, 2.4 ± 1.1 kg. The mean ERI was 11.0 ± 1.6 [Table 1].
Table 1: Details of the study participants.

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Among the group studied, 16.7% had hypo-thyroidism, 2.3% had hyperthyroidism, and 10.9% had subclinical hypothyroidism.

Sex, vascular access type, previous transplantation, presence of diabetes mellitus, mode of dialysis, frequency of intradialytic hypotension, type of ESA given, and age did not affect free T4 and TSH levels. TSH level was significantly higher in hypertensive patients than in nonhypertensive patients (3.1 ± 3.3 and ± 1.5 mIU/L, respectively; P <0.05), in those with a serum albumin level <50th percentile (3.6 ± 4.4 and 2.6 ± 1.8 mIU/L, respectively; P = 0.05), in those with weekly dialysis hours < 50th percentile (3.9 ± 5.3 and 2.6 ± 1.8 mIU/L, respectively), and in those with a lower ERI (3.7 ± 4.4 and 2.4 ± 1.9, respectively; P = 0.05) [Table 2].
Table 2: Impact of certain parameters on thyroid-stimulating hormone and T4 levels

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On the other hand, FT4 was higher in patients with greater interdialytic weight gain (13.4 ± 4.3 and 11.8 ± 2.2 pmol/L, respectively; P = 0.009) and in patients with a higher pre-HD DBP (13.2 ± 4.0 and 12.0 ± 2.9 mm Hg, respectively; P = 0.05) [Table 2].

We found negative correlations between TSH level and the following parameters: URR (r = 0.29, P = 0.002), serum albumin (r = 0.304, P = 0.001), Hgb (r = 0.26, P = 0.005), total weekly hours of dialysis, and ERI (r = 0.2, P = 0.002).


   Discussion Top


Among our study group, 16.7% had hypothyroidism and 2.3% had hyperthyroidism. Furthermore, 10.9% also had subclinical hypothyroidism, which was previously reported to occur in 12.5% of patients on HD.[1],[5]

TSH levels were higher in hypertensive patients than in nonhypertensive patients. This could be explained by the fact that thyroid hormones play a role in adrenergic receptor regulation and synthesis.[14],[15],[16] Increasing peripheral vascular resistance in hypothyroidism patients through increased alpha-receptor feedback contributes to BP elevation.[17],[18],[19] Hypo-thyroid patients also have autonomic nervous system dysfunction that decreases dopami-nergic activity, which enhances norepinephrine release and contributes to hypertension in those patients.[19],[20],[21],[22]

We found that the TSH level was higher in patients with fewer dialysis hours. Previous reports stated that T3 and T4 levels were lower in patients receiving less dialysis.[21],[23],[24] Shantha et al[25] reported that patients with sub-clinical hypothyroidism on HD had significantly lower serum albumin levels than patients with normal TSH levels. We found that higher TSH levels were associated with higher resistance to EPO, indicating that TSH level should be among the measured parameters when EPO resistance is observed.

We found that the predialysis DBP was higher in patients with higher free T4. This could be explained by the fact that the thyroid hormone nuclear receptors determine the activation of myocyte-specific genes that increase the synthesis of different cardiac proteins and associated with cardiac hypertrophy.[26] In addition, the reduction of systemic vascular resis-tance and afterload by T3 decreases BP, leading to activation of the renin–angiotensin–aldosterone system that contributes to the characteristic increase of cardiac output in hyperthyroidism.[27]

The limitations of this study include its small number of patients and its cross-sectional nature.


   Conclusion Top


Hypothyroidism is much more prevalent among HD patients than in the general population. Our results demonstrated that a higher TSH level was associated with hypertension, lower albumin level, and fewer weekly dialysis hours. It is also associated with increased resistance to EPO. TSH level was negatively correlated with dialysis adequacy, serum albumin, Hgb level, and ERI. It would be useful to determine whether lowering the TSH level would increase the Hgb level and decrease EPO resistance and interdialytic weight gain.

Conflict of interest: None declared.

 
   References Top

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Lim VS. Thyroid function in patients with chronic renal failure. Am J Kidney Dis 2001; 38:S80-4.  Back to cited text no. 2
    
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Beckers C, Van Ypersele de Strihou, Coche E, Troch R, Malvaux P. Iodine metabolism in severe renal insufficiency. J Clin Endocrinol Metab 1969;29:293-6.  Back to cited text no. 3
    
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Brenner B, Fandrey J, Jelkmann W. Serum immunoreactive erythropoietin in hyper-and hypothyroidism: Clinical observations related to cell culture studies. Eur J Haematol 1994; 53:6-10.  Back to cited text no. 6
    
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Bilezikian JP, Loeb JN. The influence of hyperthyroidism and hypothyroidism on alpha-and beta-adrenergic receptor systems and adrenergic responsiveness. Endocr Rev 1983;4: 378-88.  Back to cited text no. 15
    
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Fregly MJ, Nelson EL Jr., Resch GE, Field FP, Lutherer LO. Reduced beta-adrenergic responsiveness in hypothyroid rats. Am J Physiol 1975;229:916-24.  Back to cited text no. 16
    
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Williams RS, Lefkowitz RJ. Thyroid hormone regulation ofadrenergic receptors: Studies in the rat myocardium. J Cardiovasc Pharmacol 1979;1:181-9.  Back to cited text no. 18
    
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Hauger-Klevene JH, Brown H, Zavaleta J. Plasma renin activity in hyper and hypothyroidism: Effect of adrenergic blocking agents. J Clin Endocrinol Metab 1972;34:625-9.  Back to cited text no. 19
    
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Savdie E, Stewart JH, Mahony JF, Hayes JM, Lazarus L, Simons LA. Circulating thyroid hormone levels and adequacy of dialysis. Clin Nephrol 1978;9:68-72.  Back to cited text no. 21
    
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Malyszko J, Malyszko JS, Pawlak K, Mysliwiec M. Thyroid function, endothelium, and inflammation in hemodialyzed patients: Possible relations? J Ren Nutr 2007;17:30-7.  Back to cited text no. 22
    
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Sakurai S, Hara Y, Miura S, et al. Thyroid functions before and after maintenance hemodialysis in patients with chronic renal failure. Endocrinol Jpn 1988;35:865-76.  Back to cited text no. 23
    
24.
Diekman MJ, Harms MP, Endert E, Wieling W, Wiersinga WM. Endocrine factors related to changes in total peripheral vascular resistance after treatment of thyrotoxic and hypothyroid patients. Eur J Endocrinol 2001 ;144: 339-46.  Back to cited text no. 24
    
25.
Shantha GP, Kumar AA, Bhise V, Khanna R, Sivagnanam K, Subramanian KK, et al. Prevalence of subclinical hypothyroidism in patients with end-stage renal disease and the role of serum albumin: A cross-sectional study from South India. Cardiorenal Med 2011;1: 255-60.  Back to cited text no. 25
    
26.
Ganong WF. Thyroid hormones and renin secretion. Life Sci 1982;30:561-9.  Back to cited text no. 26
    
27.
Haro JM, Sabio JM, Vargas F. Renal beta-adrenoceptors in thyroxine-treated rats. J Endocrinol Invest 1992;15:605-8.  Back to cited text no. 27
    

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Correspondence Address:
Prof. Abdulla Ahmed Al Sayyari
Department of Medicine, King Saud Bin Abdulaziz University for Health Sciences, P. O. Box 22490, Riyadh 11426
Saudi Arabia
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DOI: 10.4103/1319-2442.248310

PMID: 30588957

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