Integração tireoide, inflamação e sarcopenia na Doença Renal Crônica

Abstract

Thyroid dysfunction is common in chronic kidney disease (CKD) and tends to worsen with declining glomerular filtration rate (GFR), being modulated by factors such as proteinuria, malnutrition, and inflammation. In patients undergoing hemodialysis (HD), these disturbances amplify alterations in the thyroid–nutrition–muscle axis, which are associated with increased cardiovascular risk and mortality, despite the limited integrated evidence available addressing these mechanisms in this population. In this cross-sectional study, we investigated the association between thyroid function and CKD progression across different stages, analyzing its relationship with proteinuria and GFR in stages 3 and 4, as well as its interrelationships with nutritional status, inflammation, and sarcopenia in HD patients, in addition to developing a predictive model for identifying the risk of sarcopenia. The first article assessed the correlation between thyroid function and proteinuria in CKD stages 3 and 4. A total of 150 patients were included, 64 (42.6%) in stage 3 and 86 (59.3%) in stage 4, with a median age of 68 years (IQR 61–76). Median thyroid stimulating hormone (TSH), free T4 (FT4), and urinary protein-creatinine ratio (PCR) were 2.9 IU/mL (IQR 1.89–4.04), 1.26 ng/dL (IQR 1.10–1.41), and 315.5 mg/g (IQR 108.3–830), respectively. Proteinuria was detected in 91 patients (60.6%). There was a positive correlation between PCR and TSH (r = 0.23; p = 0.003) and a negative correlation between PCR and FT4 (r = –0.17; p = 0.03), suggesting that urinary protein loss may affect thyroid hormone metabolism. However, no significant differences in thyroid function were found between stages 3 and 4. The second article investigated the relationship among thyroid function, nutritional status, sarcopenia, and inflammation in 101 HD patients and 33 controls. The median age was higher in HD patients compared to controls (58 vs. 48 years, respectively). Thyroid autoimmunity was less prevalent in HD (6.9%) than in controls (18.1%). Compared with controls, HD patients exhibited higher TSH, C-reactive protein, interleukin-6, tumor necrosis factor α, and leptin levels, and lower FT3, FT4, albumin, and Geriatric Nutritional Risk Index (GNRI) values (p < 0.05), with no difference in BMI. Handgrip strength, skeletal muscle mass, and skeletal muscle mass index were significantly lower in HD patients. Sarcopenia was more frequent in HD patients (48.5% probable; 26.7% confirmed) than in controls (18.1% and 6%). Within the HD group, sarcopenic individuals showed significantly lower FT3 levels. A penalized regression model (Elastic Net) identified four independent predictors of sarcopenia: FT3, TSH, GNRI and dialysis status. Each 1 mIU/L increase in TSH raised the probability of sarcopenia by 6.6% (OR ≈ 1.07), while each 1 pg/mL increase in FT3 reduced the risk by 18% (OR ≈ 0.82). GNRI had a modest protective effect, and HD status increased the odds by 47% (OR ≈ 1.47). In summary, HD patients exhibit thyroid dysfunction, heightened inflammation, and poor nutritional status conditions closely associated with sarcopenia. FT3, TSH, GNRI and being on HD emerge as integrated risk markers for sarcopenia, underscoring the need for a multidimensional clinical approach targeting the thyroid–nutrition–muscle axis.