Relationship between Subclinical Hypothyroidism and Uremic Pruritis in Hemodialysis Patients.

BACKGROUND AND AIM: Uremic pruritus (UP) is one of the most distressing symptoms in hemodialysis (HD) patients. Subclinical hypothyroidism (SCH) is a biochemical condition with high prevalence in HD patients. The present multicentric study aimed to assess the relationship between UP and SCH in HD patients. METHODS: The present cross-sectional study included 328 HD patients. All patients were submitted to careful history through clinical examination and standard laboratory assessment. Pruritis was evaluated using the pruritis visual analog scale (VAS). Patients were diagnosed with SCH if they had TSH levels above the upper limit of the normal reference range in association with normal free thyroxine (FT4) levels. RESULTS: Among the studied patients, there were 196 patients (59.8 %) with UP. Comparison between patients with UP and patients without revealed that patients in the former group had significantly longer HD duration (median (IQR): 47.5 (27.0-72.5) versus 36.0 (23.0-50.5) months, p < 0.001) and lower Kt/v (median (IQR): 1.4 (1.09-1.7) versus 1.54 (1.12-1.91), p = 0.009). Moreover, they had significantly higher ferritin (median (IQR): 653.0 (526.0-800.0) versus 628.0 (470.8- 716.0) ng/mL), hsCRP (median (IQR): 12.0 (8.0-14.0) versus 8.0 (6.0-9.0) mg/dL, p < 0.001) and TSH levels (median (IQR): 4.34 (1.98-5.2) versus 3.34 (1.9-4.85) µIU/ml) with a significantly higher frequency of SCH (45.9 % versus 28.8 %, p = 0.002). Logistic regression analysis identified hemodialysis duration (OR (95%) CI): 1.02 (1.009-1.028), p < 0.001), ferritin levels (OR (95% CI): 1.002 (1.001-1.003), p < 0.001), and SCH (OR (95% CI): 0.54 (0.32-0.89), p = 0.016) as significant predictors of UP. CONCLUSION: The present study suggested a possible link between SCH and the development of UP in HD patients.

Relation between erythropoietin resistance and metabolic syndrome in hemodialysis patients: A multicentric propensity score matched analysis.

Erythropoietin (EPO) resistance is frequently reported in hemodialysis (HD) patients. Metabolic syndrome (MetS) is a common biochemical condition that comprises central obesity, dyslipidemia, hypertension, and hyperglycemia. The present study aimed to assess the relation between MetS and EPO resistance in HD patients. The present multicentric study included 150 patients with EPO resistance and 150 patients without EPO resistance. Short-acting EPO resistance was diagnosed if the erythropoietin resistance index is ≥1.0 IU/kg/gHb. Comparison between patients with EPO resistance and patients without resistance revealed that the former group had significantly higher body mass index, lower hemoglobin levels, lower albumin levels, higher ferritin levels, and higher high-sensitivity C-reactive protein (hsCRP) levels. In addition, patients in the EPO resistance group had significantly higher frequency of MetS (75.3% vs 38.0%, p < 0.001) and higher number of MetS components (2.7 ± 1.3 vs 1.8 ± 1.6, p < 0.001). Multivariate logistic regression analysis identified lower albumin levels (OR (95% CI): 0.072 (0.016-0.313), p < 0.001), higher ferritin levels (OR (95% CI): 1.05 (1.033-1.066), p< 0.001), higher hsCRP levels (OR (95% CI): 1.041 (1.007-1.077), p = 0.018), and MetS (OR (95% CI): 36.68 (2.893-465.05), p = 0.005) as predictors of EPO resistance in the studied patients. The present study identified MetS as a predictor of EPO resistance in HD patients. Other predictors include serum ferritin, hsCRP, and albumin levels.

Antidiabetic Potential of Novel 1,3,5-Trisubstituted-2-Thioxoimidazloidin-4-One Analogues: Insights into α-Glucosidase, α-Amylase, and Antioxidant Activities.

As the ninth leading cause of death globally, diabetes mellitus (DM) is considered to be the worst chronic metabolic disease requiring an enormous need for healthcare with over 578 million expected cases by 2023. Several recent findings have demonstrated that mediating the activity of carbohydrate-hydrolyzing enzymes, including α-amylase and α-glucosidase, could be a potential strategy for managing the development of DM. In the presented study, a novel set of 1,3,5-trisubstituted-2-thioxoimidazolidin-4-ones was designed, synthesized, and characterized. The antidiabetic activity of the synthesized compounds was explored by assessing their inhibitory activity toward α-amylase and α-glucosidase enzymes. The results demonstrated that this class of compounds exhibits considerable inhibitory activity toward both α-amylase and α-glucosidase enzymes. Among the synthesized compounds, compound 5a demonstrated the most inhibitory activity with IC50 of 5.08 and µg/mL and 0.21 µg/mL toward α-glucosidase and α-amylase activities, respectively, as compared to the drug Acarbose (IC50 = 5.76 µg/mL and 0.39 µg/mL, respectively). To gain insights into the antidiabetic potential of compound 5a, we assessed the cytotoxic and antioxidant activities. Our findings indicated that compound 5a displays considerable cytotoxicity toward WI-38 cells with an IC50 of 88.54 µg/mL, as compared to the drug Celecoxib (IC50 = 93.05 µg/mL). Further, compound 5a exhibited a high scavenging activity toward 2,2-Diphenyl1-picrylhydrazyl (DPPH) free radicals (IC50 = 51.75 µg/mL) and showed a low potential to produce ROS as indicated by the monitoring of the generated H2O2 (132.4 pg/mL), as compared to Trolox (IC50 = 58.09 µg/mL) and Celecoxib (171.6 pg/mL). Finally, we performed extensive molecular modeling studies to affirm the binding affinity of this class of compounds to the binding pocket of α-amylase and α-glucosidase enzymes. Collectively, our findings indicate that this class of compounds, particularly compound 5a, could be utilized as a lead structure for the development of novel compounds with potential antidiabetic and antioxidant activities.