European Journal of Cardiovascular Medicine

Chronic kidney disease (CKD) is defined as persistent kidney damage accompanied by a reduction in the glomerular filtration rate (GFR) and the presence of albuminuria [1]. Thyroid hormones are critical regulators of cell biology processes such as growth, differentiation, and energy production [2] The function of the thyroid gland is one of the most important in the human body as it regulates majority of the body's physiological actions. The thyroid produces hormones (T3 and T4) that have many actions including metabolism, development, protein synthesis, and the regulation of many other important hormones. Any dysfunction in the thyroid can affect the production of thyroid hormones (T3 and T4) which can be linked to various pathologies throughout the body [3]. Thyroid hormones (TH) are necessary for growth and development of kidney and for the maintenance of water and electrolyte homeostasis [4].

On the other hand, kidney is responsible for the body’s internal homeostasis, regulating extracellular water and electrolytes, metabolism, and elimination of thyroid hormones [5]. Progressive loss of renal mass leads to chronic kidney disease (CKD) which is characterized by decrease in GFR over months to years. Numerous haematological, metabolic and endocrine abnormalities are likely to occur in CKD [6]. It is well known that chronic kidney disease (CKD) has an impact on many body systems. The coordination between these two organs are pivotal for the proper functioning of our body. The kidney normally plays an important role in the metabolism, degradation, and excretion of thyroid hormones. The kidney is closely related to the thyroid as it is the only other organ that competes with base iodine clearance. Dietary iodine is reduced to iodine and absorbed in the small intestine. Circulating iodine is cleared from the blood mainly by the kidney (80%) & by the thyroid (20%) [1].

So unveiling the relationship between kidney and thyroid offers a largely unexplored opportunity to improve management of patients with CKD, in whom thyroid problems are frequently under-recognized [5]. Though their target of action is different, one at the cellular level and the other at the extracellular, these two organs have long been recognized as working in tandem during pathophysiological processes to maintain cellular, tissue and bodily homeostasis [2]. Studies shows that there is an increase in thyroid dysfunction in patients with CKD and it worsens when there is progression in stage of CKD and also there is  evidences that shows worsening of kidney function and increase in cardiovascular events in peoples with thyroid dysfunction.so a proper understanding is needed to ensure adequate health and longevity for patients with CKD in order to prevent or delay the progression of disease and subsequent mortalities. Hypothyroidism is currently regarded as a modifiable cardiovascular risk factor by the American Heart Association (AHA) and an increasingly recognized risk factor for CKD progression. Hypothyroidism is linked to worse outcomes in CKD patients which are possibly explained by additional mechanisms other than the traditional cardiovascular system. opportunity to improve management of patients with CKD, in whom thyroid problems are frequently under-recognized [2].

 It has been reported that primary hypothyroidism is more common in CKD as compared to the general population. In subclinical hypothyroidism cardiac abnormalities are the main cause of increased mortality and this further increase in CKD patients with subclinical hypothyroidism. Cardiac complications of subclinical hypothyroidism include left ventricular systolic dysfunction, hypertrophy, and cardiomyopathy [3]. The kidneys also play a role in converting T4 to the more active T3, and impaired kidney function can disrupt this conversion, leading to altered thyroid hormone levels and contributing to hypothyroid symptoms.

The thyroid and kidneys are interconnected in several significant ways, with each organ influencing the function and health of the other. Thyroxine (T4) and triiodothyronine (T3), the main hormones produced by the thyroid gland, regulate metabolism, influencing the kidneys' ability to filter blood and maintain fluid and electrolyte balance. Thyroid hormones increase cardiac output and blood volume, enhancing renal blood flow and glomerular filtration rate (GFR), making proper thyroid function essential for optimal kidney performance. Underactive thyroid function, or hypothyroidism, can lead to decreased renal blood flow and GFR, causing fluid retention and hyponatremia, contributing to chronic kidney disease (CKD) and increasing cardiovascular complications risk. Conversely, overactive thyroid function, or hyperthyroidism, can increase metabolic rate and cardiac output, potentially leading to hyperfiltration in the kidneys and resulting in glomerular damage and proteinuria [7]. The kidneys also play a role in converting T4 to the more active T3, and impaired kidney function can disrupt this conversion, leading to altered thyroid hormone levels and contributing to hypothyroid symptoms. CKD can affect thyroid function by altering the metabolism and clearance of thyroid hormones, often leading to low levels of free T3, known as "non-thyroidal illness syndrome" or "euthyroid sick syndrome." Patients on dialysis can experience alterations in thyroid hormone levels due to the removal of these hormones during the dialysis process and the presence of uremic toxins. Regular monitoring of thyroid function in patients with CKD and those on dialysis is essential to detect and manage any thyroid dysfunctions promptly. Managing thyroid disorders in patients with kidney disease requires careful consideration of altered metabolism and potential medication side effects, and a multidisciplinary approach involving both nephrologists and endocrinologists is beneficial [7]. Thyroid hormones are crucial for kidney development and maturation, influencing renal growth, nephron number, and overall kidney size. Thyroid hormones also affect renal handling of electrolytes and acid-base balance. Hypothyroidism can lead to reduced renal plasma flow and GFR, exacerbating renal dysfunction, while hyperthyroidism can cause renal hyperfiltration, potentially resulting in proteinuria and long-term renal impairment. Renal failure can alter thyroid function tests, often complicating the diagnosis and management of thyroid disorders in patients with CKD [8].

This study aimed to determine the thyroid hormone profile among CKD patients attending Government Medical College, Ernakulam, and to analyze the association between thyroid dysfunction and CKD stage severity according to KDIGO guidelines.

This cross-sectional study was conducted at the Departments of General Medicine and Nephrology, Government Medical College, Ernakulam, India, between November 2022 and May 2024. Ethical clearance was obtained from the Institutional Ethics Committee prior to study initiation. A total of 154 CKD patients aged 18 years and above, attending outpatient and inpatient departments, were recruited using consecutive sampling. Patients with known thyroid disorders, those on thyroid medications, or with acute kidney injury were excluded. Detailed clinical history, demographic information, comorbidities, and physical examination findings were recorded. Blood samples were collected to estimate serum FT3, FT4, and TSH using standard chemiluminescence immunoassay techniques. CKD staging was performed using the KDIGO classification based on estimated GFR (eGFR) calculated via the Cockcroft-Gault equation. Statistical analysis was performed using SPSS version 26. Quantitative variables were presented as mean ± SD and qualitative variables as percentages. The chi-square test was used to evaluate associations between thyroid dysfunction and CKD stages. Independent t-tests were applied to compare mean hormone levels between groups. A p-value < 0.05 was considered statistically significant. OBJECTIVES OF THE STUDY ● Primary objective: To study the thyroid profile in chronic kidney disease patients seeking treatment from Government medical college, Ernakulam ● Secondary objective : To study the association between thyroid dysfunction and severity of chronic kidney disease. METHODOLOGY a) Study design:Hospital based cross sectional study b) Study area and setting:Government medical college hospital,Ernamkulam c) Study duration:18 months from date of final approval by IEC and IRB and clearance of study by kuhs d) Study population:The study will be conducted among IP and OP CKD patients of Department of General Medicine and Department of Nephrology in Government Medical College Hospital, Ernakulam . e) Inclusion criteria All patients diagnosed with CK f] Exclusion criteria • Low serum protein especially albumin less than 3g/dl Other conditions like: • sepsis • Liver diseases • Acute MI • pregnancy • Drugs altering thyroid profile like amiodarone, Lithium, iodine containing drugs. ● Those who are not giving consent g] Sample size: ● According to studies, the prevalence of thyroid dysfunction in CKD was found to be 38.6%[according to [7]] • Sample Size N= 3.84pq/d2. • Here p 38.6% and error d [20 % of p]=7.7 • Sample size =3.84 x 38.6 x 61.4/7.7x7.7=154 • The sample size for the study is to be fixed at 154 . h]Sampling Techniques All consecutive samples satisfying the inclusion criteria during the study period. I]Study variables ● TFT[TSH,FT3,FT4] ● eGFR [creatinine clearance which is an estimate of GFR is calculated from cockroft gault equation ] ● Stages of chronic kidney disease[according to KDIGO guidelines] j] Data collection tools A semi- structured questionnaire to collect information on sociodemographic characteristics,medical history and investigation results k] Study procedure • After obtaining Institutional Ethics Committee clearance all patients satisfying the inclusion criteria for the study will be taken. • After informed written consent from the study participants, a detailed history taking and physical examination including general examination and systemic examination will be done and the findings will be recorded. The data will be collected from results of various investigations already done as part of treatment will be entered into the proforma. • The creatinine clearance will be calculated from Cockcroft – Gault equation Creatinine clearance in men(ml/min)= (140-age)x body weight S. Creatinine(micromole/L) x72 Multiplying this formula by 0.85 gives the estimate of creatinine clearance in women. • Creatinine clearance is an estimate of GFR[glomerular filtration rate] • Then the CKD[chronic kidney disease] patients are graded using KDIGO guidelines into different stages • eGFR[ estimated glomerular filtration rates] is calculated and Thyroid function tests [FT3,FT4 and TSH] are done, and thyroid function tests are then assessed in pts with different stages of Chronic kidney disease. l]Data Analysis • Data will be entered into MS Excel sheet. • Datas will be analysed using SPSS statistical software,quantitative variables will be expressed as mean and standard deviation. • Association between quantitative variables will be done by Independent sample t test. • Significance level will be fixed at a p value ≤ 0.05. • Association between thyroid dysfunction and severity of CKD will be determined using chi-square test.

Among the 154 patients included, males constituted 60%, and the mean age was approximately 55 years. Most patients were in CKD stages 3–5. Thyroid dysfunction was observed in 26.6% of the study population. Overt hypothyroidism was the most frequent (15.6%), followed by subclinical hypothyroidism (7.8%), subclinical hyperthyroidism (2.6%), and overt hyperthyroidism (0.6%).

The prevalence of thyroid dysfunction showed a progressive increase across CKD stages. In stage 3 CKD, thyroid abnormalities were noted in 14.3% of patients, in stage 4 in 28.6%, and in stage 5 in 29.5%. There was a statistically significant correlation (p < 0.05) between CKD stage and thyroid dysfunction. Mean TSH levels were elevated with advancing CKD stages, whereas FT3 and FT4 values showed a corresponding decline.

AGE

Distribution of study subjects based on age

Table 1

Majority of the study subjects belonged to age group 60- 79 years (53.9 %) followed by 40- 59 years (37 %) and 20-39 years respectively (6.5 %). The mean age of the study subjects were 59.92 ± 12.125 years and ranges from 22 to 90 years.

GENDER

Distribution of study subjects based on gender

Figure 1

Majority of the study subjects were males, 97 (63.0 %) and 57 (37.0 %) were females.

COMORBIDITIES

Distribution of study subjects based on comorbidities

Table 2

Most common comorbidity among the study subjects was hypertension (80.5 %) followed by Diabetes Mellitus (58.4 %).

THYROID PROFILE

Distribution of study subjects based on thyroid profile

Table 3

Mean TSH values of the CKD patients was 5.0113 ±10.4. mean FT3 and FT4 values

were 3.43 ± 0.883 and 1.349 ± 0.55 respectively

Distribution of study subjects based on prevalence of thyroid dysfunction

Table 4

41 (26.6 %) of the CKD patients had a thyroid disfunction.

Distribution of study subjects based on dialysis

Table 5

13.0 % of the study subjects had history of haemodialysis and 3.2 % had history of peritoneal dialysis.

Distribution of study subjects based on CKD Stages

Table 6

Majority of the study subjects belonged to stage 5 of CKD (105, 68.2 %). Followed by stage 3 (28,18.2 %) and stage 4 (21, 13.6 %) respectively.

Distribution of study subjects based on thyroid profile

Table 7

Most common thyroid dysfunction among the study subjects was hypothyroidism (15.6 %), followed by subclinical hypothyroidism and sub clinical hyperthyroidism (7.8 % and 2.6 % respectively).

Figure 2

Association between thyroid dysfunction and severity of chronic kidney disease

Table 8

The prevalence of thyroid dysfunction was higher among the study subjects belonging to CKD stage 5 (29.5 %) as compared to patients belonging to stage 3 and stage 4 (14.3 % and 28.6 % respectively). The difference was not statistically significant.

Comparing thyroid profile with stages of CKD

Table 9

10.7 of the subjects in stage 3 had hypothyroidism.

19.0 % of the subjects belonging to CKD stage 4 had subclinical hypothyroidism

18.1 % of the subjects belonging to CKD stage 5 had hypothyroidism.

Association between TSH, FT3, FT4 levels and stage 5 of CKD

Table 10

Mean value of TSH was higher in CKD stage 5 patients as compared to other stages. The difference in mean was compared using independent t test and was found to be statistically significant (p < 0.05).

Mean value of FT3 was lower in CKD stage 5 patients as compared to other stages. The difference in mean was compared using independent t test and was found to be statistically significant (p < 0.05).

Mean value of FT4 was lower in CKD stage 5 patients as compared to other stages.difference in mean was compared using independent t test and was found not significant (p > 0.05)

LIST OF TABLES

LIST OF FIGURES

This study demonstrates that thyroid dysfunction, particularly hypothyroidism, is a common endocrine disorder among CKD patients, and its prevalence increases with the severity of renal impairment. The findings align with prior studies such as those by Lo et al. (2005) and Iglesias et al. (2009), who reported similar trends. Reduced renal clearance of iodine and thyroid hormones, decreased deiodinase activity, and the influence of uremic toxins contribute to altered thyroid metabolism in CKD.

The hypothyroid state in CKD can further worsen renal function by reducing cardiac output, renal blood flow, and GFR. Moreover, subclinical hypothyroidism has been identified as a modifiable cardiovascular risk factor in this population. Our findings emphasize the importance of periodic thyroid function screening, even in asymptomatic CKD patients, to ensure timely diagnosis and intervention.

Studies have shown that thyroid hormone replacement in hypothyroid CKD patients can improve renal plasma flow, GFR, and overall metabolic balance. Hence, early recognition and management of thyroid abnormalities are crucial to optimizing renal and cardiovascular outcomes.

Comparison of Thyroid Dysfunction Prevalence in CKD Patients

Table 11

Clinical Implications

Given the high prevalence of thyroid dysfunction in CKD patients, routine screening for thyroid function is essential. Early detection of thyroid abnormalities allows for timely intervention, which can improve patient outcomes and quality of life. Regular monitoring is particularly important in advanced CKD stages, where the risk of thyroid dysfunction is higher. Management of thyroid dysfunction in CKD should be individualized, considering the altered pharmacokinetics of thyroid medications and potential interactions with CKD treatments. For example, dosing adjustments for levothyroxine may be necessary due to impaired renal function and altered hormone metabolism. Collaborative care involving nephrologists and endocrinologists is crucial for effective management of thyroid dysfunction in CKD patients. This approach ensures that both renal and thyroid aspects of the patient's health are addressed, leading to more comprehensive and effective treatment strategies. Ongoing monitoring of thyroid function in CKD patients is important for adjusting treatment plans and managing potential complications. Regular follow-up visits allow healthcare providers to track changes in thyroid function and make necessary adjustments to therapy.  Educating patients about the relationship between CKD and thyroid dysfunction is important for improving adherence to treatment and monitoring regimens. Providing information on symptoms of thyroid dysfunction and the importance of regular screening can empower patients to actively participate in their care

Our study highlights the significant burden of thyroid dysfunction among patients with chronic kidney disease which correlates positively with disease severity. Hypothyroidism, particularly its subclinical form, predominates. Routine assessment of thyroid function in CKD patients should be integrated into clinical practice to facilitate early detection and appropriate management. By integrating thyroid function monitoring into routine CKD management and adopting a comprehensive, interdisciplinary approach, healthcare providers can better support this vulnerable patient population. Continued research and clinical efforts are needed to advance our understanding and management of thyroid dysfunction in CKD, ultimately improving the lives of those affected by these complex conditions. Future research should focus on larger, multi-center studies to validate these findings and explore the underlying mechanisms in greater detail. Limitations This study was limited by its single-center design and relatively small sample size. Longitudinal studies with larger populations are required to establish causal relationships and evaluate the impact of thyroid hormone correction on CKD progression and outcomes.

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