Correlation between subclinical hypothyroidism and renal function in patients with diabetes mellitus

Zhang, Lin; Yang, Gangyi; Su, Zhiyan; Jy, Yang

doi:10.1111/nep.12852

Cited by 7 publications

(3 citation statements)

References 18 publications

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“…Previous studies reported that both hypothyroidism and hyperthyroidism worsen kidney function directly by affecting renal blood flow, GFR, tubular function, electrolyte homeostasis, electrolyte pump functions, and kidney structure (e.g., decreased glomerular volume and area) and increasing peripheral vascular resistance [14][15][16], leading to higher serum CR concentrations and a lower eGFR. Several researchers also found an association of subclinical hypothyroidism with renal injury, such as macroalbuminuria in DM subjects [32][33][34][35]. Similarly, in our current study, the prevalence of these three kidney disorders was significantly different when all participants were grouped by the reference range of TSH, the distribution of which looked like a "U" shape.…”

Section: Discussionsupporting

confidence: 80%

Thyroid Parameters and Kidney Disorder in Type 2 Diabetes: Results from the METAL Study

Chen

Zhang

Wang

et al. 2020

Journal of Diabetes Research

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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.

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Section: Discussionsupporting

confidence: 80%

Thyroid Parameters and Kidney Disorder in Type 2 Diabetes: Results from the METAL Study

Chen

Zhang

Wang

et al. 2020

Journal of Diabetes Research

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“…Cr clearance (Ccr) and urinary albumin excretion rate (UAER) were calculated as previously. 50 All measurements were done in duplicate for n = 10 rats/group.…”

Section: Biochemical Analysismentioning

confidence: 99%

Salidroside protects against diabetes mellitus‐induced kidney injury and renal fibrosis by attenuating TGF‐β1 and Wnt1/3a/β‐catenin signalling

Shati

Alfaifi

2020

Clin Exp Pharma Physio

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This study evaluated if the nephroprotective effect of Salidroside in type 1 diabetes mellitus (T1DM) involves modulation of Wnt/β‐catenin signalling pathways. Control or Streptozotocin (STZ, 50 mg/kg, iv)‐induced T1DM adult male Wister rats were treated with the vehicle and Salidroside (100 mg/kg, orally) for 8 weeks daily. As compared to T1DM‐induced rats, Salidroside improved kidney structure, reduced urinary protein and albumin level, increased creatinine clearance, and suppressed renal fibrosis. It also decreased mRNA and protein levels of Wnt1, Wnt3, and TGF‐β1, phosphorylation of Smad‐3, total and nuclear levels of β‐catenin, and levels and activities of cleaved caspase‐3. Concomitantly, Salidroside significantly increased the levels of p‐β‐catenin (Ser33/37/Thr41) and suppressed protein levels of Axin‐2, fibronectin, and, mRNA and protein levels of collagen IIIa, the main targets of β‐catenin. In both control and T1DM rats, Salidroside significantly lowered fasting glucose levels and reduced renal levels of reactive oxygen species (ROS) p‐and GS3Kβ (Ser9) but significantly increased levels of SOD and GSH. In conclusion, Salidroside protected the kidney of rats against T1DM‐induced injury and fibrosis by activating GS3Kβ‐induced inhibition of Wnt1/Wnt3a β‐catenin. This was associated with hypoglycaemic and antioxidant effects.

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“…P rimary hypothyroidism is characterized by a high concentration of thyrotropin (TSH) concomitant with concentrations of thyroid hormones being low (overt) or within the reference range (subclinical). In conventional nongenetic observational studies, both overt and subclinical hypothyroidism are associated with increased plasma creatinine, decreased estimated glomerular filtration rate (eGFR), chronic kidney disease (CKD), and increased urinary albumin/creatinine ratio (UACR) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Overt hypothyroidism is most often an autoimmune disease in adults, (13) affecting predominantly middle-aged and older women.…”

Section: Introductionmentioning

confidence: 99%

Hypothyroidism and Kidney Function: A Mendelian Randomization Study

Ellervik

Mora

Ridker

et al. 2020

Thyroid

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Background: Uncertainty in the mechanism and directionality of observational associations between thyroid function and kidney function may be addressed by genetic analysis with an instrumental variable method termed bidirectional Mendelian randomization (MR). Methods: In the Women's Genome Health Study (WGHS), observational associations between thyroid measures and kidney function were evaluated. Genetic instruments for MR were from recent genome-wide association studies (GWAS) of hypothyroidism, thyrotropin (TSH), and free thyroxine (fT4) concentrations within the reference range, thyroid peroxidase antibodies (TPOAb), estimated glomerular filtration rate from creatinine (eGFR crea ), eGFR from cystatin C (eGFR cys ), and chronic kidney disease (CKD). In WGHS individual-level data, these instruments were used for bidirectional MR between thyroid (N = 3336) and kidney (N = 23,186) functions. To increase power, MR was also performed using GWAS summary statistics from the Chronic Kidney Disease Genetics Consortium (CKDGen) for eGFR crea (N = 567,460), eGFR cys (N = 24,063), CKD [N(total) = 480,698, N(cases) = 41,395], and urinary albumin/creatinine ratio (UACR/N = 54,450). Results: In the WGHS, hypothyroidism was observationally associated with decreased eGFR crea [beta (standard error, SE): -0.024 (0.009) ln(mL/min/1.73 m 2 ), p = 0.01]. By MR, hypothyroidism was associated with decreased eGFR crea in the WGHS [beta (SE): -0.007 (0.002) per doubled odds hypothyroidism, p = 1.7 • 10 -3 ] and in CKDGen [beta (SE): -0.004 (0.0005), p = 2.0 • 10 -22 ], and robust to sensitivity analysis. Hypothyroidism was also associated by MR with increased CKD in CKDGen (odds ratio, OR [confidence interval,

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Correlation between subclinical hypothyroidism and renal function in patients with diabetes mellitus

Abstract: These findings demonstrate an association of SCH with renal injury in diabetic patients.

Cited by 7 publications

References 18 publications

Thyroid Parameters and Kidney Disorder in Type 2 Diabetes: Results from the METAL Study

Thyroid Parameters and Kidney Disorder in Type 2 Diabetes: Results from the METAL Study

Salidroside protects against diabetes mellitus‐induced kidney injury and renal fibrosis by attenuating TGF‐β1 and Wnt1/3a/β‐catenin signalling

Hypothyroidism and Kidney Function: A Mendelian Randomization Study

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