Deciphering the Role of Thyroid Hormones in Severe Non-ADPKD Chronic Kidney Disease
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 51
- 试验地点
- 1
研究概览
简要总结
This is a retrospective, observational, study evaluating circulating thyroid hormone profiles in patients with severe chronic kidney disease (CKD stages G4-G5, non-dialysis). The study includes one cohort of patients with non-ADPKD CKD and a second including a matched subset of patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) at the same CKD stage,.
For the non-ADPKD CKD group, serum and urine samples will be retrieved from the certified biobank of the Centro Daccò (Mario Negri IRCCS). For the ADPKD group, analyses will be performed exclusively using existing clinical and laboratory data available within the REORIENTED study database.
Laboratory measurements will be performed on stored biological samples from the non-ADPKD CKD group to assess thyroid hormones (rT3, fT3, tT3, fT4, tT4, and TSH). Clinical and laboratory data for both cohorts will be obtained from the respective study databases and linked within a predefined temporal window relative to sample collection (where applicable).
详细描述
Chronic kidney disease (CKD) is frequently associated with alterations in thyroid hormone homeostasis, commonly referred to as Non-Thyroidal Illness Syndrome (NTIS) or "low T3 syndrome" . This condition is typically characterized by reduced circulating levels of free triiodothyronine (fT3) in the presence of normal or slightly decreased Thyroid-Stimulating Hormone (TSH) and free thyroxine (fT4), and has been associated with inflammation, protein-energy wasting, and the severity of renal dysfunction.
While these hormonal changes are generally interpreted as an adaptive metabolic response to chronic illness, accumulating evidence suggests that alterations in thyroid hormone metabolism in CKD may reflect more complex pathophysiological mechanisms, including impaired peripheral deiodination, mitochondrial dysfunction, chronic inflammation, and altered availability of enzymatic cofactors.
In this context, reverse triiodothyronine (rT3), a thyroid hormone metabolite generated through peripheral deiodination of thyroxine (T4), has been proposed as a potential marker of altered thyroid hormone metabolism. Although rT3 is not routinely used in clinical practice, it may provide additional insights into the balance between activating and inactivating pathways of thyroid hormone metabolism, particularly when interpreted in combination with fT3 (e.g., rT3/fT3 ratio).
Recent findings from the REORIENTED study conducted in a well-characterized cohort of patients with autosomal dominant polycystic kidney disease (ADPKD), identified a distinct thyroid hormone profile characterized by increased rT3 levels, reduced fT3 concentrations, and a significant association between both fT3 and rT3 levels and renal function, measured as estimated glomerular filtration rate (eGFR). These relationships were particularly strong in patients with moderate to severe kidney dysfunction, who exhibit an increased rT3/fT3 ratio compared to patients with normal to mild decrease in eGFR, probably due to an increased conversion of T4 into rT3 at the expense of the production of fT3.
These observations raise the hypothesis that ADPKD may be associated with disease-specific alterations in thyroid hormone profile, potentially reflecting unique features of cystic kidney disease. However, it remains unclear whether this hormonal pattern is specific to ADPKD or rather represents a general feature of advanced CKD, independent of the etiology.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non-ADPKD CKD
- •CKD stage G4, included in the ADAPT study
- •Availability of stored serum and urine samples in the biobank suitable for thyroid hormone analysis
- •Availability of relevant clinical and laboratory data within a predefined time window from sample collection
- •Signed informed consent for storage and future research use of biological samples and clinical data
- •ADPKD CKD
- •CKD stage G4, included in the REORIENTED study
- •Availability of complete thyroid hormone profile and relevant clinical data
排除标准
- •(applied to both groups as far as possible)
- •Known history of thyroid disease (hypothyroidism, hyperthyroidism, thyroiditis, or thyroid cancer)
- •Treatment with thyroid hormone replacement or antithyroid drugs
- •Use of medications known to interfere with thyroid function (e.g., amiodarone, lithium, interferon)
- •Systemic corticosteroid or immunosuppressive therapy at the time of sampling (if data available)
- •Dialysis treatment or history of kidney transplantation at the time of sampling
- •Acute illness, infection, or hospitalization close to the time of sample collection (if identifiable)