Objective. We investigated the effect of roxadustat on factors associated with renal fibrosis and efficacy. Methods. Sixty patients meeting the inclusion criteria between January 2021 and October 2021 were equally distributed into observation (roxadustat) group and control (Erythropoietin) group. Then, the expression of serum hypoxia-inducible factor 1-alpha (HIF-1α), transforming growth factor-β (TGF-β1), vascular endothelial growth factor (VEGF), fibronectin (FN), and collagen Ⅳ (C-IV) was compared at different time points (baseline, 2-week follow-up, and 4-week follow-up). The improvement degree of hemoglobin (Hb) and the change level of iron parameters and hepcidin were also compared between the two groups. Results. In the roxadustat group, the expression of HIF-1α at 2 weeks was significantly higher than the baseline and approached the baseline value at 4 weeks. At 4 weeks, TGF-β1 and FN expression was significantly lower than baseline. In addition, the improvement of Hb in the roxadustat group was significantly higher than that in the control group at 4 weeks, and the change of ferritin, transferrin, and hepcidin indexes from baseline was better than in the control group. Conclusion. After giving roxadustat, it can change the expression of HIF-1α, TGF-β1, and FN. Its efficacy is superior to EPO, which is worthy of clinical application.
Background The impact of metabolically healthy obesity (MHO) on kidney dysfunction remains debatable. Moreover, few studies have focused on the early stages of kidney dysfunction indicated by hyperfiltration and mildly reduced eGFR. Thus, we aimed to investigate the association between the MHO and early kidney dysfunction, which is represented by hyperfiltration and mildly reduced estimated glomerular filtration rate (eGFR), and to further explore whether serum uric acid affects this association. Methods This cross-sectional study enrolled 1188 residents aged ≥ 40 years old from Yonghong Communities. Metabolically healthy phenotypes were categorized based on Adult Treatment Panel III criteria. Obesity was defined as body mass index (BMI) ≥ 25 kg/m2. Mildly reduced eGFR was defined as being in the range 60 < eGFR ≤ 90 ml/min/1.73m2. Hyperfiltration was defined as eGFR > 95th percentile after adjusting for sex, age, weight, and height. Results Overall, MHO accounted for 12.8% of total participants and 24.6% of obese participants. Compared to metabolically healthy non-obesity (MHNO), MHO was significantly associated with an increased risk of mildly reduced eGFR (odds ratio [OR] = 1.85, 95% confidence interval [CI] 1.13–3.01) and hyperfiltration (OR = 2.28, 95% CI 1.03–5.09). However, upon further adjusting for uric acid, the association between the MHO phenotype and mildly reduced eGFR was reduced to null. Compared with MHNO/non-hyperuricemia, MHO/non-hyperuricemia was associated with an increased risk of mildly reduced eGFR (OR = 2.04, 95% CI 1.17–3.58), whereas MHO/hyperuricemia was associated with an observably increased risk (OR = 3.07, 95% CI 1.34–7.01). Conclusions MHO was associated with an increased risk of early kidney dysfunction, and the serum uric acid partially mediated this association. Further prospective studies are warranted to clarify the causality.
Diabetic nephropathy (DN) is one of the most common complications of diabetes. Gradual loss of podocytes is a sign of DN and pyroptosis mechanistically correlates with podocyte injury in DN; however, the mechanism(s) involved remain unknown. Here we reveal that TRIM29 is overexpressed in high glucose (HG)‐treated murine podocytes cells and that TRIM29 silencing significantly inhibits podocyte damage due to HG treatment, as evidenced by lower desmin expression and greater nephrin expression. Additionally, flow cytometry analysis showed that TRIM29 silencing significantly inhibited HG treatment‐induced pyroptosis, which was confirmed by immunoblotting for NLRP3, active Caspase‐1, GSDMD‐N, and phosphorylated NF‐κB‐p65. Conversely, overexpression of TRIM29 could trigger pyroptosis that was attenuated by NF‐κB inhibition, indicating that TRIM29 promotes pyroptosis through the NF‐κB pathway. Mechanistic studies revealed that TRIM29 interacts with IκBα to mediate its ubiquitination‐dependent degradation, which in turn leads to NF‐κB activation. Taken together, our data demonstrate that TRIM29 can promote podocyte pyroptosis by activating the NF‐κB/NLRP3 pathway. Thus, TRIM29 represents a potentially novel therapeutic target that may also be clinically relevant in the management of DN.
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