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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2018  |  Volume : 29  |  Issue : 4  |  Page : 911-915
The effect of hypothyroidism on serum irisin level in patients with nondiabetic chronic kidney disease: A pilot study with a cross-sectional design


1 Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
2 Department of Nephrology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
3 Department of Preventive and Social Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

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Date of Submission10-Jul-2017
Date of Decision18-Aug-2017
Date of Acceptance22-Aug-2017
Date of Web Publication28-Aug-2018
 

   Abstract 

Both chronic kidney disease (CKD) and hypothyroidism are associated with decreased serum irisin level. The presence of hypothyroidism may influence serum irisin level in CKD patients. The objective of this study was to evaluate the effect of hypothyroidism on serum irisin level in patients with nondiabetic CKD. Two hundred nondiabetic CKD patients aged between 18 and 65 years with glomerular filtration rate <60 mL/min/1.73 m2 were included in this study. Forty-three (21.5%) patients had hypothyroidism (overt and subclinical both). Forty hypothyroid and forty euthyroid CKD patients matched for age and Body Mass Index underwent body composition, biochemical [fasting plasma glucose (FPG) and C-reactive protein], and hormonal (fasting irisin and insulin) evaluation. Body composition analysis including visceral adipose tissue was done by dual-energy X-ray absorptiometry. Homeostatic model assessment 2 insulin resistance was calculated from FPG and insulin levels. The median serum irisin levels were not significantly different between hypothyroid and euthyroid CKD patients [95 (47.74–261.52) vs. 66 (28.25–224.50) ng/mL, P = 0.30]. There was also no difference in renal function, body composition and other metabolic parameters between the two groups. To conclude, the presence of hypothyroidism does not alter serum irisin level in patients with nondiabetic CKD.

How to cite this article:
Patil MM, Parameswaran S, Kamalanathan S, Sahoo JP, Balachandran K, Kar SS. The effect of hypothyroidism on serum irisin level in patients with nondiabetic chronic kidney disease: A pilot study with a cross-sectional design. Saudi J Kidney Dis Transpl 2018;29:911-5

How to cite this URL:
Patil MM, Parameswaran S, Kamalanathan S, Sahoo JP, Balachandran K, Kar SS. The effect of hypothyroidism on serum irisin level in patients with nondiabetic chronic kidney disease: A pilot study with a cross-sectional design. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Oct 14];29:911-5. Available from: http://www.sjkdt.org/text.asp?2018/29/4/911/239642

   Introduction Top


Chronic kidney disease (CKD) is emerging as an important disease of public health importance. Its prevalence is estimated to be 8%–16% worldwide.[1] CKD is associated with cardiovascular diseases due to various metabolic abnormalities such as insulin resistance, dyslipidemia, and altered body composition.[2] The risk factors for these abnormalities are poor nutrition, uremia, acidosis, proinflam-matory cytokines, and alteration of the renin-angiotensin-aldosterone activity.[2] However, the pathogenesis is not completely understood, and the alterations in serum irisin level may contribute to these changes.

Irisin is a proteolytic cleavage product of fibronectin type III domain containing protein 5 (FNDC 5) present in the muscle.[3] It is thought to mediate the beneficial effects of exercise on adipose tissue.[4] Subsequently; it was shown that it is not only a myokine but also an adipokine.[5] It improves various metabolic parameters by stimulating the browning of the white adipose tissue.

The CKD patients are at a higher risk of developing hypothyroidism as compared to the general population.[6] Both CKD and hypothy-roidism are associated with decreased serum irisin level.[7],[8],[9],[10],[11],[12],[13],[14] Therefore, the presence of hypothyroidism may further decrease serum irisin level in CKD subjects. The aim of this study was to evaluate the effect of hypothy-roidism on serum irisin level in patients with nondiabetic CKD. In addition, the factors such as body composition and metabolic parameters, which are associated with altered serum irisin level, were also compared between CKD patients with and without hypothyroidism.


   Materials and Methods Top


This study was carried out in Endocrinology and Nephrology Departments of a tertiary care health center in India. The adult CKD patients attending Nephrology outpatient department were screened for inclusion and exclusion criteria. The inclusion criteria were: age between 18 and 65 years with CKD (stage 3 to 5). The estimated glomerular filtration rate (GFR) was calculated by DaVita GFR calculator based on the 2009 CKD-Epidemiology Collaboration equation.[15] CKD (stage 3 to 5) was defined as GFR <60 mL/min/1.73 m2 for ≥3 months: stage three-30–59 mL/min/1.73 m2, stage four-15-29 mL/min/1.73 m2 and stage five-<15 mL/min/1.73 m2. The exclusion criteria were as follows: patients on dialysis, diabetes, liver disease, malignancies, infection, congestive cardiac failure, and pregnancy. This was a pilot study, and the sample size was not calculated. Two hundred patients were included in the study after obtaining their informed consent from November 2014 to October 2015.

The study was in compliance with the Declaration of Helsinki ethical principles and was approved by the Institute Ethics Committee. The detailed history taking (associated comor-bidities, duration of CKD, and symptoms of hypothyroidism), anthropometry and physical examination were performed in all of them. The patients underwent body composition analysis by dual-energy X-ray absorptiometry (Hologic Discovery Wi). Serum creatinine, fasting plasma glucose (FPG), and thyroid function tests (TFT) were estimated in all patients. The TFT included the measurement of thyroid-stimulating hormone (TSH) and free tetra-iodothyronine (fT4) in serum. Serum irisin, insulin, and C reactive protein (CRP) were analyzed in 40 out of the 43 hypothyroid CKD patients, and an equal number of age, and Body Mass Index (BMI) matched euthyroid CKD patients. The stored serum samples in three hypothyroid patients were not fit for hormonal analysis. Serum TSH and insulin were measured by ADVIA Centaur XP Immunoassay System, Siemens Healthcare Global, USA. The hypothyroidism was subdivided into overt hypothyroidism (OH) and subclinical hypothyroidism (SCH) based on serum fT4 level irrespective of TSH value. OH was defined as TSH > 5.5 mIU/L with low fT4 (<0.89 ng/dL) and SCH was defined as TSH >5.5 mIU/L with normal fT4 (0.89 to 1.76 ng/dL). The homeostatic model assessment 2 insulin resistance (HOMA 2 IR) was calculated for the evaluation of insulin resistance.[16] Serum CRP level was measured by enzyme-linked immunosorbent assay (ELISA) kit (Ray Biotech Inc., Norcross, GA, USA). The normal level of CRP was <10 mg/L. The intra-assay coefficient of variation (CV) was <10% and inter-assay CV was <12%. Serum irisin concentration was measured in duplicate by using ELISA kits from the Cusabio biotechnology company, China. The performance of this kit is comparable to the standard commercial assay using kits from Phoenix Pharmaceuticals, USA.[17] The sensitivity of this kit was <0.78 ng/mL with the detection range of 3.12-200 ng/mL. The intra-assay CV was <8%, and the inter-assay CV was <10%.


   Statistical Analysis Top


Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 20.0 for Windows (SPSS Inc., Chicago, IL, USA). Kolmogorov–Smirnov test was used to verify the data distribution. The continuous variables were expressed as the median with interquartile range. Mann–Whitney U-test was used to find the difference between continuous variables. The categorical variables were expressed as percentages. The P <0.05 was considered significant in statistical analysis.


   Results Top


The median age of the study population was 52 years. One hundred and forty-six (73%) patients were male. The median duration of the CKD was 1.5 years. Sixty of them were in CKD stage 3, 85 were in CKD stage 4 and 55 were in CKD stage 5. The median BMI of the study population was 21 kg/m2. The prevalence of the hypothyroidism was 21.5% (43/200) with median TSH of 3.315 mIU/L. Out of 43 subjects with hypothyroidism, 37 were newly detected and drug naive. The hypothyroidism was subclinical in 79% (34/43) patients.

[Table 1] and [Table 2] show the comparison of renal function, body composition, and metabolic parameters between 40 hypothyroid and equal number of euthyroid CKD patients. The median serum irisin levels were not significantly different between hypothyroid and euthyroid CKD patients [95 (47.74–261.52) vs.66 (28.25–224.50) ng/mL, P = 0.30]. There was also no difference in FPG, insulin resistance, and inflammatory marker (CRP) between two groups [Table 2].
Table 1: The comparison of anthropometry, renal function, and thyroid function tests between hypothyroid and CKD patients.

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Table 2: The comparison of body composition and metabolic parameters between hypothyroid and euthyroid CKD patients.

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   Discussion Top


The serum irisin level in CKD patients is affected by the degree of renal dysfunction and the dialysis status.[7],[8],[10],[11] The median serum concentration of irisin decreased with worsening renal function and the serum level was the lowest in CKD stage 5 in various studies.[8],[11] There was a significant reduction in median irisin levels (by 23%) after hemo-dialysis as compared with predialysis concentrations in a study by Ebert et al.[8] This finding is in accordance with the hypothesis that irisin is at least partially dialyzable. However, the CKD patients on dialysis were not included in this study.

The uremic toxin-like indoxyl sulfate negatively regulate the expression of irisin precursor FNDC5 and irisin secretion from skeletal muscle cells.[7] In addition, increased inflammation, oxidative stress and insulin resistance associated with CKD also contribute to altered serum irisin level.[5],[7],[8],[11] Advanced CKD is characterized by progressive muscle wasting with less physical activity leading to sarco-penia, which is aggravated in the presence of hypothyroidism.[8],[11],[12] This also partly responsible for decreased irisin level in these patients as the skeletal muscle is the primary source of irisin in human beings.[5]

Low serum irisin level was found in hypothyroid patients in various studies.[12],[13],[14] The low serum irisin level in hypothyroid patients could be related to the muscle damage as irisin is negatively correlated with the serum creatine kinase level.[12],[14] Hypothyroidism also decreases serum irisin by worsening renal function.[6] The irisin concentration changes during thyroid dysfunction are time-dependent. Patients with prolonged hypothyroidism had lower serum irisin levels than those with newly detected hypothyroidism in a study by Zybek-Kocik et al.[14] Thyroid antibody positivity is also associated with lower irisin levels with greater risk of OH.[12],[14] However, we have not measured thyroid antibody in this study.

Serum irisin levels did not differ between CKD patients with or without hypothyroidism in our study. This is because the hypothyroidism was subclinical and was newly detected in most of our cases, which would have weakened the effect of thyroid hormones on serum irisin level. This is evidenced by a similar degree of renal dysfunction and body composition parameters between hypothyroid and euthyroid groups. In addition, the other factors which are associated with altered serum irisin levels like insulin resistance and degree of inflammation were also similar in the two groups.

To conclude, the presence of hypothyroidism does not alter serum irisin level in patients with nondiabetic CKD. To the best of our knowledge, this is the first study to evaluate the effect of thyroid dysfunction on serum irisin level in CKD patients. However, there are few limitations in this study. The range of TSH levels in the patients included in the study is too small. Moreover, the TSH levels in the hypothyroid group are too low to be of clinical significance. The sample size was also small in the study. Hence, attempt should be made to have large-scale studies involving CKD patients with a longer duration of hypo-thyroidism and higher levels of TSH values to be clinically relevant.

Funding: Intramural research grant from Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER).

Conflict of interest: None declared.

 
   References Top

1.
Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: Global dimension and perspectives. Lancet 2013;382:260-72.  Back to cited text no. 1
    
2.
Slee AD. Exploring metabolic dysfunction in chronic kidney disease. Nutr Metab (Lond) 2012;9:36.  Back to cited text no. 2
    
3.
Boström P, Wu J, Jedrychowski MP, et al. A PGC1-a-dependent myokine that drives brown-fat-like development of white fat and thermo-genesis. Nature 2012;481:463-8.  Back to cited text no. 3
    
4.
Gouveia MC, Vella JP, Cafeo FR, Affonso Fonseca FL, Bacci MR. Association between irisin and major chronic diseases: A review. Eur Rev Med Pharmacol Sci 2016;20:4072-7.  Back to cited text no. 4
    
5.
Perakakis N, Triantafyllou GA, Fernández-Real JM, et al. Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol 2017;13:324-37.  Back to cited text no. 5
    
6.
Iglesias P, Díez JJ. Thyroid dysfunction and kidney disease. Eur J Endocrinol 2009;160: 503-15.  Back to cited text no. 6
    
7.
Wen MS, Wang CY, Lin SL, Hung KC. Decrease in irisin in patients with chronic kidney disease. PLoS One 2013;8:e64025.  Back to cited text no. 7
    
8.
Ebert T, Focke D, Petroff D, et al. Serum levels of the myokine irisin in relation to metabolic and renal function. Eur J Endocrinol 2014;170:501-6.  Back to cited text no. 8
    
9.
Lee MJ, Lee SA, Nam BY, et al. Irisin, a novel myokine is an independent predictor for sarco-penia and carotid atherosclerosis in dialysis patients. Atherosclerosis 2015;242:476-82.  Back to cited text no. 9
    
10.
Yang S, Xiao F, Pan L, et al. Association of serum irisin and body composition with chronic kidney disease in obese Chinese adults: A cross-sectional study. BMC Nephrol 2015;16:16.  Back to cited text no. 10
    
11.
Liu JJ, Liu S, Wong MD, et al. Relationship between circulating irisin, renal function and body composition in type 2 diabetes. J Diabetes Complications 2014;28:208-13.  Back to cited text no. 11
    
12.
Ruchala M, Zybek A, Szczepanek-Parulska E. Serum irisin levels and thyroid function – Newly discovered association. Peptides 2014;60:51-5.  Back to cited text no. 12
    
13.
Yalcin MM, Akturk M, Tohma Y, et al. Irisin and myostatin levels in patients with Graves' disease. Arch Med Res 2016;47:471-5.  Back to cited text no. 13
    
14.
Zybek-Kocik A, Sawicka-Gutaj N, Wrotkowska E, Sowinski J, Ruchala M. Time-dependent irisin concentration changes in patients affected by overt hypothyroidism. Endokrynol Pol 2016;67:476-80.  Back to cited text no. 14
    
15.
GFR Calculator. The National Kidney Foundation. Available from: https://www.kidney. org/professionals/KDOQI/gfr_calculator. [Last accessed on 2015 Nov 08].  Back to cited text no. 15
    
16.
Mojiminiyi OA, Abdella NA. Effect of homeostasis model assessment computational method on the definition and associations of insulin resistance. Clin Chem Lab Med 2010; 48:1629-34.  Back to cited text no. 16
    
17.
Li M, Yang M, Zhou X, et al. Elevated circulating levels of irisin and the effect of metformin treatment in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2015;100:1485-93.  Back to cited text no. 17
    

Top
Correspondence Address:
Dr. Jaya Prakash Sahoo
Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry
India
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DOI: 10.4103/1319-2442.239642

PMID: 30152429

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