|Year : 2022 | Volume
| 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
Ayodele Ademola Adelakun1, Roland Eghoghosoa Akhigbe2, Lydia Oluwatoyin Ajayi3, Ayodeji Folorunsho Ajayi2
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 Submission||28-Mar-2022|
|Date of Acceptance||19-Apr-2022|
|Date of Web Publication||01-Jul-2022|
Dr. Ayodeji Folorunsho Ajayi
Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo-state
Source of Support: None, Conflict of Interest: None
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 2023 May 29];10:29-33. Available from: https://www.njecbonline.org/text.asp?2022/10/1/29/349559
| Introduction|| |
Chronic kidney disease (CKD) is a significant health concern that affects about 8%–16% of the global population. The prevalence varies across the globe. It has been reported to affect about 13.1% of Americans, 10.8% of Chinese,, 6.4% in Italy, and 12.4%–19% in the Democratic Republic of Congo. Although, just like in every other country, the reported prevalence varies in Nigeria with community, Odubanjo et al. 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. Although positive family history, hypertension, and diabetes are established risk factors for CKD,, 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. THs modify GFR via its effects on cardiac output and renal blood flow. The hormones also exert a direct impact on kidneys by altering GFR, tubular secretory and reabsorptive functions, and electrolyte balance.,, Hypothyroidism has been reported to cause raised serum creatinine levels following a significant decline in GFR.,,, Low THs, even within the clinically normal range, has been associated with decreased GFR., Hyperthyroidism may also play a role in the development and progression of CKD. Zhang et al. 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.,,,,, On the other hand, Meuwese et al., 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|| |
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 (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.
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. Subjects were also classified into different stages of CKD based on their eGFR using the NKF Classification Criteria.
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|| |
[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.
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|
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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|
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[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|
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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|
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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.
| Discussion|| |
Although animal and human studies have shown a strong association between altered thyroid states and cardiovascular risk factors,,, reproductive dysfunction,, hepatic injury,, and gastric mucosal injury,, the reports on the association between dysthyroidism and renal dysfunction are contradicting.,,,,,,,,, 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. 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, 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,,,, 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., 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. 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. 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. Hypothyroidism has been implicated in reducing renal blood flow,, 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.,
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 and alteration of THs. 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
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]