We investigated the effectiveness of the transforming growth factor beta-1 (TGF-β) receptor inhibitor GW788388 on the epithelial to mesenchymal transition (EMT) using human peritoneal mesothelial cells (HPMCs) and examined the effectiveness of GW788388 on the peritoneal membrane using a peritoneal fibrosis mouse model. HPMCs were treated with TGF-β with or without GW788388. Animal experiments were conducted on male C57/BL6 mice. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. GW788388 was administered by once-daily oral gavage. The morphological change, cell migration, and invasion resulted from TGF-β treatment, but these changes were attenuated by cotreatment with GW788388. TGF-β-treated HPMCs decreased the level of the epithelial cell marker and increased the levels of the mesenchymal cell markers. Cotreatment with GW788388 reversed these changes. Phosphorylated Smad2 and Smad3 protein levels were stimulated with TGF-β and the change was attenuated by cotreatment with GW788388. For the peritoneal fibrosis mice, thickness and collagen deposition of parietal peritoneum was increased, but this change was attenuated by cotreatment with GW788388. GW788388, an orally available potent TGF-β receptor type 1 inhibitor, effectively attenuated TGF-β-induced EMT in HPMCs. Cotreatment with GW788388 improved peritoneal thickness and fibrosis, and recovered peritoneal membrane function in a peritoneal fibrosis mouse model.

We investigated the effect of SB525334 (TGF-β receptor type 1 (TβRI) inhibitor) on the epithelial to mesenchymal transition (EMT) signaling pathway in human peritoneal mesothelial cells (HPMCs) and a peritoneal fibrosis mouse model. In vitro experiments were performed using HPMCs. HPMCs were treated with TGF-β1 and/or SB525334. In vivo experiments were conducted with male C57/BL6 mice. The 0.1% chlorhexidine gluconate (CG) was intraperitoneally injected with or without SB52534 administration by oral gavage. Mice were euthanized after 28 days. EMT using TGF-β1-treated HPMCs included morphological changes, cell migration and invasion, EMT markers and collagen synthesis. These pathological changes were reversed by co-treatment with SB525334. CG injection was associated with an increase in peritoneal fibrosis and thickness, which functionally resulted in an increase in the glucose absorption via peritoneum. Co-treatment with SB525334 attenuated these changes. The levels of EMT protein markers and immunohistochemical staining for fibrosis showed similar trends. Immunofluorescence staining for EMT markers showed induction of transformed cells with both epithelial and mesenchymal cell markers, which decreased upon co-treatment with SB525334. SB525334 effectively attenuated the TGF-β1-induced EMT in HPMCs. Cotreatment with SB525334 improved peritoneal thickness and fibrosis and recovered peritoneal membrane function in a peritoneal fibrosis mouse model.

Background: Our study aimed to evaluate the differences in hemoglobin variability among patients undergoing hemodialysis (HD) treated with three types of erythropoiesis-stimulating agents (ESAs) and the association between hemoglobin variability and clinical outcomes. Methods: In this study, data from the 6th and 7th HD quality assessments were used, comprising 48,726 patients in South Korea. ESAs are categorized into short-acting (epoetin alfa/beta/delta, requiring more frequent administration), intermediate-acting (darbepoetin alfa), and long-acting agents (methoxy polyethylene glycol-epoetin beta, requiring extended dosing intervals), each with distinct pharmacokinetic properties and dosing schedules. Based on use of ESA types, participants were divided into the following groups: Short, Intermediate, and Long. Hemoglobin levels were measured monthly over a 6-month assessment period. Hemoglobin variability was defined as the residual standard deviation derived from a within-subject linear regression model with six hemoglobin values for each patient. Results: The Short, Intermediate, and Long groups comprised 36,420, 10,514, and 1792 patients, respectively. The hemoglobin variability (mean [95% confidence interval]) was 0.60 (0.60–0.60), 0.68 (0.67–0.68), and 0.64 (0.62–0.65) g/dL in the Short, Intermediate, and Long groups, respectively. Multivariate and subgroup analyses revealed that the hemoglobin variability was lower in the Short group than in the other two groups. Cox regression did not show a significant association between an increase in hemoglobin variability and all-cause mortality or cardiovascular events in univariate and multivariate analyses. Conclusions: Our cohort study found that the use of short-acting ESAs showed the lowest hemoglobin variability, whereas the use of intermediate-acting ESAs showed the highest variability. In the context of South Korea’s healthcare system, where frequent hemoglobin monitoring and strict ranges are emphasized, short-acting ESAs combined with regular laboratory follow-up appeared to support more stable hemoglobin levels.

Background: Although erythropoiesis-stimulating agent (ESA) therapy is fundamental for correcting anemia, excessive ESA administration is associated with increased risks. This study aimed to investigate the impact of the erythropoietin resistance index (ERI) on clinical outcomes in a population-based cohort of hemodialysis (HD) patients. Methods: This retrospective study analyzed datasets from patients who underwent periodic HD quality assessments and their claims data. Overall, we included 35,913 patients. Participants were divided into quartiles based on the ERI during the 6-month assessment period: Q1, Q2, Q3, and Q4 groups. Results: The 5-year survival rates were 68.8% (Q1), 67.8% (Q2), 66.9% (Q3), and 60.2% (Q4) (p < 0.001). Multivariable analysis showed the same trends as the univariable analysis. Additionally, a spline curve using the multivariable model indicated that the increased ERI was linked to all-cause mortality. However, cardiovascular events were not associated with ERI quartiles in Cox regression analyses. Subgroup analysis revealed that in most subgroups, the all-cause mortality was significantly higher in those with a high ERI than in those with a low ERI. Further analysis using the balanced cohort, which attenuated baseline characteristic differences, confirmed that the high mortality in those with a high ERI was maintained. Conclusions: Our population-based cohort study reveals an association between the ERI and all-cause mortality in HD patients.

Background: There are few studies investigating the relationship between phosphate level variability and clinical prognosis in hemodialysis (HD) patients. This study aimed to evaluate the impact of phosphate variability on clinical outcomes in maintenance HD patients using a population-based cohort. Methods: We analyzed data from 55,225 patients who underwent periodic HD quality assessments and claims review. Phosphate variability was assessed using the residual standard deviation (SD) from a within-subject linear regression model based on six phosphate measurements per patient. Participants were categorized into quartiles based on phosphate variability. A balanced cohort was created using generalized boosted models for relevant covariates. Results: After weighting, the residual phosphate SDs were 0.35 ± 0.00 mg/dL (Q1), 0.57 ± 0.00 mg/dL (Q2), 0.79 ± 0.00 mg/dL (Q3), and 1.22 ± 0.00 mg/dL (Q4). The mean follow-up duration across all quartiles was 50 ± 0.2 months. Multivariable Cox regression analysis revealed that patients in the Q4 group had a significantly higher hazard ratio (HR) for all-cause mortality and dementia compared with the Q1 group. Among all quartiles, Q1 showed the lowest HR for dementia. These trends were consistent with those observed in spline curve analyses. However, no significant association was found between phosphate variability and cardiovascular events. Conclusions: High phosphate variability was associated with increased risk of all-cause mortality and dementia in maintenance HD patients.

Background: Although the risk of serious bleeding following peritoneal dialysis catheter insertion is low, pericannular bleeding can increase the risk of catheter-related infections and reduce catheter survival. We aimed to analyze the risk factors for bleeding complications during peritoneal dialysis catheter insertion and assess whether temporary preemptive hemodialysis before catheterization can reduce bleeding and improve catheter survival. Methods: We retrospectively analyzed bleeding complications and catheter survival in patients who underwent temporary hemodialysis prior to peritoneal dialysis catheter insertion. Cox regression analysis was performed to determine the risk factors for bleeding complications and catheter survival. Results: Among 336 patients, 216 and 120 comprised the non-hemodialysis and hemodialysis groups, respectively. No significant association was found between temporary hemodialysis and bleeding (hazard ratio: 1.6, 95% confidence interval: 0.87–2.95, p < 0.134). Multivariate analysis revealed an inverse association of platelet count (hazard ratio: 0.99, 95% confidence interval: 0.99–0.99, p < 0.048) and hemoglobin level (hazard ratio: 0.78, 95% confidence interval: 0.61–0.99, p < 0.04) with bleeding. A positive association was observed between international normalized ratio (hazard ratio: 2.24, 95% confidence interval: 1.19–4.19, p < 0.012) and bleeding. Conversely, temporary hemodialysis was not associated with catheter survival (hazard ratio: 1.64, 95% confidence interval: 0.63–4.25, p < 0.308). Conclusions: Temporary hemodialysis before peritoneal dialysis catheter insertion did not significantly affect bleeding risk in patients with a high risk of uremic bleeding.