Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 10  |  Issue : 1  |  Page : 29-33

Association between thyroid hormones and renal function in patients with chronic kidney disease: A hospital-based cross-sectional study among Nigerians


1 Department of Medical Laboratory Science, Babcock University, IlishanRemo, Ogun-state, Nigeria
2 Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo-state, Nigeria
3 Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo-state, Nigeria

Date of Submission28-Mar-2022
Date of Acceptance19-Apr-2022
Date of Web Publication01-Jul-2022

Correspondence Address:
Dr. Ayodeji Folorunsho Ajayi
Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo-state
Nigeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njecp.njecp_2_22

Rights and Permissions
  Abstract 


Background: A seemingly exciting link has been reported to exist between thyroid state and renal function, thus establishing a thyroid–renal axis. However, findings from studies aimed at evaluating this axis have not been consistent. Therefore, we hypothesized that estimated glomerular filtration rate (eGFR), a surrogate of incident chronic kidney disease (CKD), could be independently predicted by thyroid-stimulating hormone (TSH), free thyroxin (fT4), and free triiodothyronine (fT3). Materials and Methods: We compared the serum concentrations of TSH, fT4, and fT3 in patients with CKD after classifying them into stage III, stage IV, or end-stage renal disease based on the National Kidney Foundation Classification Criteria. Results: Our results showed that the concentrations of TSH, fT4, and fT3 were comparable across the different stages of CKD. Findings from the study also indicated that thyroid hormones were not associated with CKD, nor were they predictors of CKD development. Conclusion: The present study demonstrates that TSH, fT4, and fT3 are not effective risk factors that are independently associated with declined eGFR in patients with CKD. Our findings also revealed that these hormones are not useful tools in the early detection of CKD.

Keywords: Chronic kidney disease, electrolyte balance, thyroxin, thyroid-stimulating hormones


How to cite this article:
Adelakun AA, Akhigbe RE, Ajayi LO, Ajayi AF. Association between thyroid hormones and renal function in patients with chronic kidney disease: A hospital-based cross-sectional study among Nigerians. Niger J Exp Clin Biosci 2022;10:29-33

How to cite this URL:
Adelakun AA, Akhigbe RE, Ajayi LO, Ajayi AF. Association between thyroid hormones and renal function in patients with chronic kidney disease: A hospital-based cross-sectional study among Nigerians. Niger J Exp Clin Biosci [serial online] 2022 [cited 2022 Aug 18];10:29-33. Available from: https://www.njecbonline.org/text.asp?2022/10/1/29/349559




  Introduction Top


Chronic kidney disease (CKD) is a significant health concern that affects about 8%–16% of the global population.[1] The prevalence varies across the globe. It has been reported to affect about 13.1% of Americans, 10.8% of Chinese,[2],[3] 6.4% in Italy,[4] and 12.4%–19% in the Democratic Republic of Congo.[5] Although, just like in every other country, the reported prevalence varies in Nigeria with community, Odubanjo et al.[6] documented a prevalence of 1.6%–12.4% in Nigeria. This noncommunicable disease is associated with 8–10-fold rise in the risk for cardiovascular mortality and a risk multiplier in diabetic and hypertensive patients.[7] Although positive family history, hypertension, and diabetes are established risk factors for CKD,[8],[9] the identification of more predisposing factors for CKD would play a key role in better understanding the pathogenesis as well as the progression of CKD, employing newer prevention strategies, and possibly develop new therapeutic horizons.

Thyroid hormones (THs) have been reported to influence the risk for CKD susceptibility via a rapid decline in estimated glomerular filtration rate (eGFR), a determinant of CKD development and progression.[10] THs modify GFR via its effects on cardiac output and renal blood flow.[11] The hormones also exert a direct impact on kidneys by altering GFR, tubular secretory and reabsorptive functions, and electrolyte balance.[12],[13],[14] Hypothyroidism has been reported to cause raised serum creatinine levels following a significant decline in GFR.[15],[16],[17],[18] Low THs, even within the clinically normal range, has been associated with decreased GFR.[19],[20] Hyperthyroidism may also play a role in the development and progression of CKD. Zhang et al.[21] in their prospective cohort study in South Korea observed that high levels of thyroid-stimulating hormone (TSH) in euthyroid subjects were associated with greater risk of CKD. They reported that normal-to-high levels of TSH and normal-to-low levels of free triiodothyronine (fT3) were associated with an increased risk of CKD in euthyroid subjects. This is consistent with previous studies.[11],[20],[22],[23],[24],[25] On the other hand, Meuwese et al.[22],[26] reported a nonsignificant association between low thyroid function and alteration in renal function.

In the light of these conflicting reports, this study sought to assess the link between THs and renal function in a hospital-based cross-sectional study.


  Materials and Methods Top


Study design

The study was a hospital-based cross-sectional study that was conducted over 2 years among patients diagnosed with CKD attending the nephrology outpatient clinic and those admitted to the nephrology ward in a teaching hospital in Southwestern Nigeria.

Subjects and ethical issues

A total number of 120 subjects who fulfilled the inclusion criteria and gave their consent were recruited for the study. The study obtained prior approval of the ethical committee of the institution.

Patients above 20 years and diagnosed of CKD based on medical history, clinical examination, and National Kidney Foundation (NKF) Criteria[27] (kidney disease of a minimum of 3 months duration, structural and functional abnormality as revealed by serum urea or creatinine; urine examination or imaging study) were included in the study. Patients with a family history of a thyroid disorder, history of thyroid replacement therapy, or history of any surgery or any radiological intervention on thyroid disorder were excluded.

Sample collection

Five milliliters of venous blood was collected from each participant and was used for the determination of serum urea, creatinine, electrolytes (sodium, potassium, chloride, and bicarbonate), TSH, and thyroxin (fT3 and free T4 [fT4]). Serum urea and creatinine were measured using Cobas C111 analyzer (ROCHE, Germany). Serum electrolytes were measured using ion-selective electrode 6000 analyzer (SFRI, France). Serum TSH, fT3, and fT4 were estimated using enzyme-linked immunosorbent assay technique with kits supplied by Accubind.

Subjects were classified as euthyroid, subclinical hypothyroidism, and overt hypothyroidism based on their thyroid function test result as described by Khandelwal and Tandon.[28] Subjects were also classified into different stages of CKD based on their eGFR using the NKF Classification Criteria.

Statistical analysis

Analysis was done using IBM SPSS v20 Armonk, New York, USA. Data are presented in the form of mean ± standard error of mean. One-way analysis of variance followed by Tamhane post hoc test for pairwise comparison was used to evaluate the differences between THs and stages of CKD. Spearman's bivariate correlation was done to assess the relationship between THs and indices of renal function. To evaluate whether or not THs are determinants of eGFR, multivariate linear regression was done. P < 0.05 was considered statistically significant.


  Results Top


[Figure 1] shows the age distribution of the study participants. 13.33% of the participants were between 20 and 39 years, while 25.83% were at least 60 years old. The majority (60.83%) of the studied subjects were between 40 and 59 years.
Figure 1: Age distribution of participants

Click here to view


Among the studied individuals, 60.83% were euthyroid, 34.165% were subclinically hypothyroid, while 5% were overtly hypothyroid [Figure 2]. 60.27% of the euthyroid patients, 68.29% of subclinical hypothyroid patients, and 50% of overt hypothyroid patients were male [Figure 3].
Figure 2: Characterization of subjects according to age and thyroid hormones

Click here to view
Figure 3: Characterization of participants based on gender

Click here to view


Of the euthyroid patients, 9.5% had stage III CKD, 61.64% had stage IV CKD, while 28.76% had end-stage renal disease (ESRD). Of the subclinical hypothyroid patients, 4.85% had stage III CKD, 78% had stage IV CKD, while 17.07% had ESRD. Similarly, of the overt hypothyroid patients, 0% had stage II CKD, 66.66% had stage IV CKD, while 33.33% had ESRD [Figure 4].
Figure 4: Association between dysthyroidism and stages of chronic kidney disease

Click here to view


[Figure 5] shows the serum concentrations of THs in various stages of CKD. Although TSH was higher in stage IV and ESRD than in stage III, this was not statistically significant. fT3 and fT4 were also comparable across the various stages of CKD.
Figure 5: Serum levels of thyroid hormones in various stages of chronic kidney disease

Click here to view


TSH level was negatively correlated with serum urea, creatinine, and eGFR; however, the correlation observed was not significant. Similarly, fT4 and fT3 were negatively correlated with eGFR, but these were not also statistically significant [Table 1].
Table 1: Correlation between thyroid hormones and renal function indices

Click here to view


Multiple linear regression analysis results are shown in [Table 2]. Findings from this analysis showed that TSH, fT4, and fT3 are not predictors of eGFR in CKD patients.
Table 2: Multivariate regression in the studied population

Click here to view



  Discussion Top


Although animal and human studies have shown a strong association between altered thyroid states and cardiovascular risk factors,[29],[30],[31] reproductive dysfunction,[32],[33] hepatic injury,[34],[35] and gastric mucosal injury,[36],[37] the reports on the association between dysthyroidism and renal dysfunction are contradicting.[11],[20],[21],[22],[23],[24],[25],[26],[38],[39] In the present hospital-based prospective study, we observed that high concentrations of TSH were marginally associated with renal function decline; this was not significant. One of the significant findings of our study was that elevated levels of TSH were observed in stage IV and ESRD when compared with stage III, but these were not statistically significant. Furthermore, no significant associations were found between TSH, fT3, fT4, and serum urea and creatinine, and eGFR. Findings from this study also show that TSH, fT3, and fT4 are not determinants of eGFR. To the best of our understanding, the present study seems to be the first to establish that TH is neither associated with nor predictors of renal function decline in the Nigerian population.

The decline in eGFR is a known independent predisposing factor for renal dysfunction and a surrogate for the development of CKD.[10] This explains why the NKF classifies CKD into various stages based on eGFR. Although there was an increase in TSH in patients with stage IV and ESRD when compared with patients with stage III which is in tandem with previous studies,[23] this increase was not statistically significant in the present study. Similarly, fT3 and fT4 were comparable in patients in various stages of CKD. Contrary to previous studies,[22],[23],[24],[25] the present study also revealed that neither TSH nor fT3 and fT4 is an efficient predictor of eGFR.

Furthermore, in our study, we observed that elevated levels of THs were not significantly associated with raised serum urea and creatinine. The result suggests that when higher or lower than normal thyroid hormone levels are obtained in clinical practice, it may not necessarily have any connection with an impaired renal function. Our findings are consistent with several previous observations.[20],[26] An individual participant data meta-analysis from 16 cohorts having measured TSH, fT4 levels, and creatinine levels revealed that hypothyroidism was not associated with renal dysfunction.[26] Furthermore, an earlier population-based prospective follow-up study of an 85-year-old inhabitant of Leiden, The Netherlands, demonstrated that higher levels of TSH and lower levels of fT3 and fT4 are associated with lower renal function at baseline; over time, this association was absent.[20] Findings from this study question the etiopathogenic and prognostic relevance of thyroid status in CKD.

Although some studies established a strong link between thyroid dysfunction and renal impairment, the associated mechanisms remain poorly elucidated. It has been speculated that hyperthyroidism led to increased permeability of the glomerular barrier and consequent proteinuria.[40] Hypothyroidism has been implicated in reducing renal blood flow,[14],[41] hence results in poor glomerular perfusion with a possible decrease in glomerular filtration. The variation in our observations when compared to previous studies that established a link between THs and renal function might be due to the definitions of CKD. In the present study, CKD was defined based on eGFR and not eGFR and albuminuria, which could be triggered by dysthyroidism.[15],[17]

Moreover, the discrepancy seen may be due to the age range of the patients. It is a known fact that increasing age is associated with declined renal function[42] and alteration of THs.[43] Furthermore, ethnicity/race may also explain the differences observed.

The major limitation of the present study was the definition of CKD by eGFR only rather than eGFR and albuminuria. Second, the subject size may not allow for a generalization of the current findings. Finally, this was not a follow-up study as only the baseline findings of the patients were documented. However, the strength of this study must be acknowledged. The study was not a retrospective study, hence allowed adjustment for possible confounders and eliminated bias. Furthermore, the study recruited patients across a wide range of age group. This study shows that TSH, fT3, and fT4 may not be useful screening tools in the early discovery of the loss of renal function.

Summarily, results from our study imply that TSH, fT4, and fT3 are not associated with increased risk of CKD development; neither is they predictors of CKD incidence or prognosis. Further studies aimed at validating the findings of the present study across various ages and ethnic groups in larger population size to assess the link between THs and incident CKD and possible associated mechanisms are recommended.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. Chronic kidney disease: Global dimension and perspectives. Lancet 2013;382:260-72.  Back to cited text no. 1
    
2.
Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, et al. Prevalence of chronic kidney disease in the United States. JAMA 2007;298:2038-47.  Back to cited text no. 2
    
3.
Zhang L, Wang F, Wang L, Wang W, Liu B, Liu J, et al. Prevalence of chronic kidney disease in China: A cross-sectional survey. Lancet 2012;379:815-22.  Back to cited text no. 3
    
4.
Cirillo M, Laurenzi M, Mancini M, Zanchetti A, Lombardi C, De Santo NG. Low glomerular filtration in the population: Prevalence, associated disorders, and awareness. Kidney Int 2006;70:800-6.  Back to cited text no. 4
    
5.
Sumaili EK, Krzesinski JM, Zinga CV, Cohen EP, Delanaye P, Munyanga SM, et al. Prevalence of chronic kidney disease in Kinshasa: Results of a pilot study from the Democratic Republic of Congo. Nephrol Dial Transplant 2009;24:117-22.  Back to cited text no. 5
    
6.
Odubanjo MO, Oluwasola AO, Kadiri S. The epidemiology of end-stage renal disease in Nigeria: The way forward. Int Urol Nephrol 2011;43:785-92.  Back to cited text no. 6
    
7.
Couser WG, Remuzzi G, Mendis S, Tonelli M. The contribution of chronic kidney disease to the global burden of major non-communicable diseases. Kidney Int 2011;80:1258-70.  Back to cited text no. 7
    
8.
Levey AS, Coresh J. Chronic kidney disease. Lancet 2012;379:165-80.  Back to cited text no. 8
    
9.
James MT, Hemmelgarn BR, Tonelli M. Early recognition and prevention of chronic kidney disease. Lancet 2010;375:1296-309.  Back to cited text no. 9
    
10.
Tohidi M, Hasheminia M, Mohebi R, Khalili D, Hosseinpanah F, Yazdani B, et al. Incidence of chronic kidney disease and its risk factors, results of over 10 year follow up in an Iranian cohort. PLoS One 2012;7:e45304.  Back to cited text no. 10
    
11.
Chuang M, Liao K, Hung Y, Wang PY, Chou Y, Chou P. Abnormal thyroid-stimulating hormone and chronic kidney disease in elderly adults in Taipei city. J Am Geriatr Soc 2016;64:1267-73.  Back to cited text no. 11
    
12.
den Hollander JG, Wulkan RW, Mantel MJ, Berghout A. Correlation between severity of thyroid dysfunction and renal function. Clin Endocrinol (Oxf) 2005;62:423-7.  Back to cited text no. 12
    
13.
Katz AI, Emmanouel DS, Lindheimer MD. Thyroid hormone and the kidney. Nephron 1975;15:223-49.  Back to cited text no. 13
    
14.
Villabona C, Sahun M, Roca M, Mora J, Gómez N, Gómez JM, et al. Blood volumes and renal function in overt and subclinical primary hypothyroidism. Am J Med Sci 1999;318:277-80.  Back to cited text no. 14
    
15.
Basu G, Mohapatra A. Interactions between thyroid disorders and kidney disease. Indian J Endocrinol Metab 2012;16:204-13.  Back to cited text no. 15
    
16.
Mohamedali M, Reddy Maddika S, Vyas A, Iyer V, Cheriyath P. Thyroid disorders and chronic kidney disease. Int J Nephrol 2014;2014:520281.  Back to cited text no. 16
    
17.
Iglesias P, Díez JJ. Thyroid dysfunction and kidney disease. Eur J Endocrinol 2009;160:503-15.  Back to cited text no. 17
    
18.
Mariani LH, Berns JS. The renal manifestations of thyroid disease. J Am Soc Nephrol 2012;23:22-6.  Back to cited text no. 18
    
19.
Gopinath B, Harris DC, Wall JR, Kifley A, Mitchell P. Relationship between thyroid dysfunction and chronic kidney disease in community-dwelling older adults. Maturitas 2013;75:159-64.  Back to cited text no. 19
    
20.
Asvold BO, Bjøro T, Vatten LJ. Association of thyroid function with estimated glomerular filtration rate in a population-based study: The HUNT study. Eur J Endocrinol 2011;164:101-5.  Back to cited text no. 20
    
21.
Zhang Y, Chang Y, Ryu S, Cho J, Lee WY, Rhee EJ, et al. Thyroid hormone levels and incident chronic kidney disease in euthyroid individuals: The Kangbuk Samsung Health Study. Int J Epidemiol 2014;43:1624-32.  Back to cited text no. 21
    
22.
Meuwese CL, Gussekloo J, de Craen AJ, Dekker FW, den Elzen WP. Thyroid status and renal function in older persons in the general population. J Clin Endocrinol Metab 2014;99:2689-96.  Back to cited text no. 22
    
23.
Tanaka Y, Furusyo N, Kato Y, Ueyama T, Yamasaki S, Ikezaki H, et al. Correlation between thyroid stimulating hormone and renal function in Euthyroid Residents of Japan: Results from the Kyushu and Okinawa Population Study (KOPS). J Atheroscler Thromb 2018;25:335-43.  Back to cited text no. 23
    
24.
Schairer B, Jungreithmayr V, Schuster M, Reiter T, Herkner H, Gessl A, et al. Effect of thyroid hormones on kidney function in patients after kidney transplantation. Sci Rep 2020;10:2156.  Back to cited text no. 24
    
25.
Zhang Y, Wang Y, Tao XJ, Li Q, Li FF, Lee KO, et al. Relationship between thyroid function and kidney function in patients with type 2 diabetes. Int J Endocrinol 2018;2018:1871530.  Back to cited text no. 25
    
26.
Meuwese CL, van Diepen M, Cappola AR, Sarnak MJ, Shlipak MG, Bauer DC, et al. Low thyroid function is not associated with an accelerated deterioration in renal function. Nephrol Dial Transplant 2019;34:650-9.  Back to cited text no. 26
    
27.
Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis 2014;63:713-35.  Back to cited text no. 27
    
28.
Khandelwal D, Tandon N. Overt and subclinical hypothyroidism: Who to treat and how. Drugs 2012;72:17-33.  Back to cited text no. 28
    
29.
Pasqualetti G, Tognini S, Polini A, Caraccio N, Monzani F. Is subclinical hypothyroidism a cardiovascular risk factor in the elderly? J Clin Endocrinol Metab 2013;98:2256-66.  Back to cited text no. 29
    
30.
Napoli R, Guardasole V, Zarra E, D'Anna C, De Sena A, Lupoli GA, et al. Impaired endothelial- and nonendothelial-mediated vasodilation in patients with acute or chronic hypothyroidism. Clin Endocrinol (Oxf) 2010;72:107-11.  Back to cited text no. 30
    
31.
Ajayi AF, Akhigbe RE, Ajayi LO. Activation of cardiac TNF-α in altered thyroid state-induced cardiometabolic disorder. J Cardiovasc Dis Res 2017;8:151-6.  Back to cited text no. 31
    
32.
Ajayi AF, Akhigbe RE, Ajayi LO. Hypothalamic-pituitary-ovarian Axis in Thyroid Dysfunction. West Indian Med J 2013;62:835-8.  Back to cited text no. 32
    
33.
Krassas GE, Pontikides N, Kaltsas T, Papadopoulou P, Paunkovic J, Paunkovic N, et al. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf) 1999;50:655-9.  Back to cited text no. 33
    
34.
Ajayi AF, Akhigbe RE. Implication of altered thyroid state on liver function. Thyroid Res Pract 2012;9:84-7.  Back to cited text no. 34
  [Full text]  
35.
Soylu A, Taskale MG, Ciltas A, Kalayci M, Kumbasar AB. Intrahepatic cholestasis in subclinical and overt hyperthyroidism: Two case reports. J Med Case Rep 2008;2:116.  Back to cited text no. 35
    
36.
Ajayi AF, Adelakun AA, Akhigbe RE. Gastric mucosa damage and impairment of secondary immune response in dysthyroidism is associated with TNF-α expression. Int J Biol Med Res 2017;8:6063-9.  Back to cited text no. 36
    
37.
Ajayi AF, Akhigbe RE, Ajayi LO, Adeleye GS, Adebayo-Gege GI. Serum and gastric tissue electrolyte levels in carbimazole-treated and levothyroxine-treated male New Zealand white rabbits. World J Pharm Pharm Sci 2018;7:142-55.  Back to cited text no. 37
    
38.
Ajayi AF, Akhigbe RE, Ajayi LO. Influence of thyroid dysfunction on Urea/Creatinine ratio: Possible role of TNF-α and IL-6. Int J Med Biomed Res 2018;7:94-102.  Back to cited text no. 38
    
39.
Ajayi AF, Akhigbe RE, Ajayi LO. Lipid peroxidation and enzymatic antioxidant activities in the kidneys of experimental dysthyroid rabbits: An assessment of renal redox state. Int J Infect Trop Dis 2019;5:16-23.  Back to cited text no. 39
    
40.
Vargas F, Moreno JM, Rodríguez-Gómez I, Wangensteen R, Osuna A, Alvarez-Guerra M, et al. Vascular and renal function in experimental thyroid disorders. Eur J Endocrinol 2006;154:197-212.  Back to cited text no. 40
    
41.
Elgadi A, Verbovszki P, Marcus C, Berg UB. Long-term effects of primary hypothyroidism on renal function in children. J Pediatr 2008;152:860-4.  Back to cited text no. 41
    
42.
Hemmelgarn BR, Zhang J, Manns BJ, Tonelli M, Larsen E, Ghali WA, et al. Progression of kidney dysfunction in the community-dwelling elderly. Kidney Int 2006;69:2155-61.  Back to cited text no. 42
    
43.
Waring AC, Arnold AM, Newman AB, Bùzková P, Hirsch C, Cappola AR. Longitudinal changes in thyroid function in the oldest old and survival: The cardiovascular health study all-stars study. J Clin Endocrinol Metab 2012;97:3944-50.  Back to cited text no. 43
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
   Abstract
  Introduction
   Materials and Me...
  Results
  Discussion
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed292    
    Printed8    
    Emailed0    
    PDF Downloaded37    
    Comments [Add]    

Recommend this journal