Background: This study aims to compare the effects of short- and intermediate-acting erythropoiesis-stimulating agents (ESAs) on hemoglobin (Hb) variability in patients undergoing maintenance hemodialysis. Methods: This retrospective cohort study included 119 patients who were classified into two groups based on ESA type: short-acting ESA (epoetin alfa/beta [EPO], n=48) and intermediate-acting ESA (darbepoetin alfa [DPO], n=71). Hb levels were measured 11 times at 4-week intervals from ESA therapy initiation to 40 weeks of follow-up. This study used established metrics from previous research, including standard deviation (SD), coefficient of variation (CV), and residual SD, to quantify Hb variability. Results: Over the 40-week study period with 4-week measurement intervals, mean Hb levels were comparable between the two ESA groups. In the EPO and DPO groups, SD was 0.67±0.19 g/dL and 0.69±0.22 g/dL, respectively (p=0.516), CV was 0.06±0.02 and 0.07±0.02, respectively (p=0.480), and residual SD was 0.73±0.21 g/dL and 0.76±0.26 g/dL, respectively (p=0.463). No significant differences in Hb variability were observed between the groups over 40 weeks using SD, CV, and residual SD. Conclusion This retrospective cohort study showed comparable mean Hb levels and Hb variability indices between groups. With respect to Hb variability, the findings reveal no clear basis for prioritizing either short-acting or intermediate-acting ESA.

This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

Glucagon-like peptide 1 receptor agonists (GLP-1RA) significantly reduce the risk of cardiovascular disease. However, whether GLP-1RA improves clinically important renal outcomes is still unclear. In cardiovascular outcome trials of GLP-1RA, renal outcomes have been evaluated as secondary outcomes; however, their benefits have not been clarified, except for the effect of reducing albuminuria. Recently, the FLOW trial evaluated the renal benefits of GLP-1RA as a primary outcome in patients with diabetes and chronic kidney disease and showed a significant renoprotective effect. In this review, we discuss the renoprotective effects of GLP-1RA, summarize recently published research results, and describe the known mechanism of renal benefit and outlook.

Glucagon-like peptide 1 receptor agonists (GLP-1RA) significantly reduce the risk of cardiovascular disease. However, whether GLP-1RA improves clinically important renal outcomes is still unclear. In cardiovascular outcome trials of GLP-1RA, renal outcomes have been evaluated as secondary outcomes; however, their benefits have not been clarified, except for the effect of reducing albuminuria. Recently, the FLOW trial evaluated the renal benefits of GLP-1RA as a primary outcome in patients with diabetes and chronic kidney disease and showed a significant renoprotective effect. In this review, we discuss the renoprotective effects of GLP-1RA, summarize recently published research results, and describe the known mechanism of renal benefit and outlook.

Glucagon-like peptide 1 receptor agonists (GLP-1RA) significantly reduce the risk of cardiovascular disease. However, whether GLP-1RA improves clinically important renal outcomes is still unclear. In cardiovascular outcome trials of GLP-1RA, renal outcomes have been evaluated as secondary outcomes; however, their benefits have not been clarified, except for the effect of reducing albuminuria. Recently, the FLOW trial evaluated the renal benefits of GLP-1RA as a primary outcome in patients with diabetes and chronic kidney disease and showed a significant renoprotective effect. In this review, we discuss the renoprotective effects of GLP-1RA, summarize recently published research results, and describe the known mechanism of renal benefit and outlook.

Glucagon-like peptide 1 receptor agonists (GLP-1RA) significantly reduce the risk of cardiovascular disease. However, whether GLP-1RA improves clinically important renal outcomes is still unclear. In cardiovascular outcome trials of GLP-1RA, renal outcomes have been evaluated as secondary outcomes; however, their benefits have not been clarified, except for the effect of reducing albuminuria. Recently, the FLOW trial evaluated the renal benefits of GLP-1RA as a primary outcome in patients with diabetes and chronic kidney disease and showed a significant renoprotective effect. In this review, we discuss the renoprotective effects of GLP-1RA, summarize recently published research results, and describe the known mechanism of renal benefit and outlook.

Insulin resistance is prevalent in chronic kidney disease and may accelerate the progression of chronic kidney disease. This study aimed to investigate whether insulin resistance is associated with the development of incident chronic kidney disease in a population with normal renal function. Methods: A total of 3,331 participants from a community-based cohort with normal renal function were prospectively analyzed. We determined the relationship of insulin resistance indices with the incident chronic kidney disease using the Cox proportional hazard model and Kaplan-Meier survival analysis. Results: During a mean follow-up of 11.03 ± 4.22 years, incident chronic kidney disease occurred in 414 participants (12.4%). The high homeostasis model assessment-insulin resistance level group had an increased risk of incident chronic kidney disease (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.13–1.74; p = 0.002) compared to the normal group after adjustment for age, sex, history of hypertension, body mass index, total cholesterol, alcohol drinking status, smoking status, and baseline estimated glomerular filtration rate. The risk of incident chronic kidney disease also increased with the lower quantitative insulin sensitivity check index level (HR, 0.62; 95% CI, 0.41–0.92; p = 0.02) and higher leptin-adiponectin ratio level (HR, 1.23; 95% CI, 1.06–1.42; p = 0.006). Conclusion: Higher insulin resistance indices are associated with the incidence of chronic kidney disease. Our data suggest that increased insulin resistance may be involved in the development of incident chronic kidney disease in a population with normal renal function.

Sepsis-associated acute kidney injury (SA-AKI) is a prominent sepsis complication, often resulting in adverse clinical outcomes. Hyperbaric oxygen therapy (HBOT), known for its anti-inflammatory characteristics, antioxidant effects, and ability to deliver high oxygen tension to hypo-perfused tissues, offers potential benefits for SA-AKI. This study investigated whether HBOT improved renal injury in sepsis and elucidated its underlying mechanisms. Methods: A lipopolysaccharide (LPS)-induced endotoxemia model was established using 8-week-old C57BL/6 mice. Thirty minutes post-LPS administration, a group of mice underwent HBOT at a 2.5 atmospheric pressure absolute with 100% oxygen for 60 minutes. After 24 hours, all mice were euthanized for measurements. Results: Our results demonstrated that HBOT effectively mitigated renal tubular cell apoptosis. Additionally, HBOT significantly reduced phosphorylated p53 proteins and cytochrome C levels, suggesting that HBOT may attenuate renal apoptosis by impeding p53 activation and cytochrome C release. Notably, HBOT preserved manganese-dependent levels of superoxide dismutase, an antioxidant enzyme, compared to the LPS group. Furthermore, transforming growth factor beta (TGF-β)/Smad4 and alpha smooth muscle actin expressions were significantly reduced in the LPS + HBOT group. Conclusion: An early single session of HBOT exhibited renoprotective effects in LPS-induced endotoxemia mice models by suppressing p53 activation and cytochrome C levels to mitigate apoptosis. The observed TGF-β decrease, downstream Smad expression reduction, and antioxidant capacity preservation following HBOT may contribute to these effects.

Fabry disease (FD) is an X-linked lysosomal disorder caused by α-galactosidase A enzyme activity deficiency. Although glycosphingolipid analogs have been identified in the plasma or urine of patients with FD, there is a limited understanding of altered metabolomics profiles beyond the globotriaosylceramide accumulation in FD. Methods: Metabolomics study was performed for monitoring of biomarker and altered metabolism related with disease progression in serum and urine from male α-galactosidase A knockout mice and age-matched wild-type mice at 20 and 40 weeks. Profiling analysis for metabolites, including organic acids, amino acids, fatty acids, kynurenine pathway metabolites, and nucleosides in the serum and urine was performed using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry combined with star symbol patterns and partial least squares discriminant analysis (PLS-DA). Results: A total of 27 and 23 metabolites from the serum and urine of FD mice were distinguished from those of wild-type mice, respectively, based on p-value (<0.05) and variable importance in projection scores (>1.0) of PLS-DA. In the serum, metabolites of the glutathione, glutathione disulfide, citrulline, and kynurenine pathways that are related to oxidative stress, nitric oxide biosynthesis, and inflammation were increased, whereas those involved in pyruvate and tyrosine metabolism and the tricarboxylic acid cycle were altered in the 20- and 40-week-old urine of FD model mice. Conclusion: Altered metabolic signatures associated with disease progression by oxidative stress, inflammation, nitric oxide biosynthesis, and immune regulation in the early and late stages of FD.