Abstract
Objective Diabetic kidney disease is one of the most common microvascular complications of diabetes mellitus. We aimed to analyze the association of thyroid parameters with kidney disorders, especially in euthyroid participants. Methods The data were obtained from a cross-sectional study, the METAL study. Thyroid parameters, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), thyroxin (T4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb), of 4136 participants with type 2 diabetes were measured. Two structure parameters of thyroid homeostasis, including the sum activity of step-up deiodinases (SPINA-GD) and thyroid secretory capacity (SPINA-GT), and two pituitary thyrotropic function indices, including Jostel's TSH index (TSHI) and the thyrotroph thyroid hormone resistance index (TTSI), were also calculated. Kidney disorders were described according to the presence of reduced estimated glomerular filtration rate (eGFR) and/or higher urinary albumin to creatinine ratio (UACR). Results The prevalence of kidney disorders increased with decreasing FT3 or T3 and increasing FT4 or T4 quartile levels (all P < 0.05). After full adjustment, linear regression showed that UACR levels were negatively associated with FT3 and T3 (P < 0.001). In addition, eGFR was positively associated with FT3 and T3 and was negatively associated with TSH and FT4 levels and TgAb positivity (all P < 0.05). By using binary logistic regression, higher TSH and FT4 and lower FT3 and T3 were associated with kidney disorders (all P < 0.05). Similar results were seen in sensitivity analyses, which were performed in 3035 euthyroid diabetic participants; however, TSH was no longer related to them. The area under the receiver operating characteristic curve (AUROC) of lower FT3 for existing kidney disorder was greater than that for any other thyroid hormones (all P < 0.001). The cutoff value of FT3 for reduced eGFR was 4.39 pmol/L. Regarding thyroid homeostasis parameters, SPINA-GD was negatively associated with three statuses of kidney disorders, and TSHI and TTSI were positively associated with reduced eGFR (all P < 0.05). Conclusions Among patients with type 2 diabetes, elevated TSH and FT4 (or T4), lower FT3 (or T3), TgAb positivity, lower SPINA-GD, and higher TSHI and TTSI were associated with kidney disorders. The lower FT3, even within the normal range (<4.38 pmol/L), may be the factor most related to reduced eGFR compared with other thyroid hormones in diabetic patients.
Highlights
Diabetes mellitus (DM) and its complications have become highly prevalent and have gained increasing attention [1], especially in developing countries
Given that thyroid status was associated with kidney disease risk factors (UACR and estimated glomerular filtration rate (eGFR)), we evaluated the adjusted odds ratios (ORs) for the prevalence of kidney disorder status
We found that the area under the receiver operating characteristic curve (AUROC) for FT3 was 0.742 for reduced eGFR, 0.552 for higher urinary albumin to creatinine ratio (UACR), and 0.571 for higher UACR and/or reduced eGFR, which was higher than other thyroid parameters (Table 3)
Summary
Diabetes mellitus (DM) and its complications have become highly prevalent and have gained increasing attention [1], especially in developing countries. Chronic kidney disease (CKD) is defined by the sustained presence of reduced kidney function or damage, often resulting from diabetes mellitus (DM) and hypertension [3]. Diabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes mellitus and the leading cause of end-stage renal disease (ESRD) worldwide [7]. Reduced estimated glomerular filtration rate (eGFR) and higher urinary albumin to creatinine ratio (UACR) levels are two main markers of diabetic kidney status, quantifying renal function and serving as a proxy of renal damage severity, respectively [3, 9]
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