Immediate-start peritoneal dialysis without break-in-period: an 18-year retrospective cohort study on patient survival.

Background: Immediate-start peritoneal dialysis (ISPD) is an effective renal replacement therapy that can prevent central venous catheterization due to its immediate initiation of peritoneal dialysis (PD) after catheter insertion without a break-in period. This study aimed to investigate the effect of ISPD on long-term patient survival. Methods: In this retrospective single-center cohort study, 178 consecutive patients who started PD from August 2005 to March 2023 were enrolled, from whom 144 patients with ISPD were analyzed. PD was initiated without a break-in period within 24 hours of catheter insertion using percutaneous needle-guidewire technique. The primary outcome was patient survival, estimated using the Kaplan-Meier method. A Cox proportional hazard regression model was used to identify factors independently associated with patient survival. Results: The median follow-up period was 4.00 years (interquartile range, 1.23‒5.75 years). The mean age of patients was 61.6 ± 13.6 years; 58 patients (40.3%) were male and 93 patients (64.6%) were diabetic. Overall patient survival rates at 1, 3, 5, and 10 years were 98.5%, 93.5%, 92.1%, and 65.6%, respectively. The technique survival rates at 1, 3, 5, and 10 years were 88.1%, 74.9%, 63.2%, and 40.2%, respectively. The peritonitis-free survival rates at 1, 3, 5, and 10 years were 92.3%, 76.0%, 59.4%, and 28.0%, respectively. In the multivariate analysis, diabetes was the only factor associated with patient survival and technique survival. Conclusion: Our study demonstrated that patient survival and technique survival rates were relatively high in ISPD patients who were catheterized using percutaneous needle-guidewire technique.

Comparison of Humoral Response between Third and Fourth Doses of COVID-19 Vaccine in Hemodialysis Patients.

Dialysis patients are more likely to die or become hospitalized from coronavirus disease 2019 (COVID-19). Currently, only a few studies have evaluated the efficacy of a fourth booster vaccination in hemodialysis (HD) patients and there is not enough evidence to recommend for or against a fourth booster vaccination. This study compared the humoral response and disease severity of patients on HD who received either three or four doses of COVID-19 vaccine. A total of 88 patients were enrolled. Humoral response to vaccination was measured by quantifying immunoglobulin G levels against the receptor binding domain of SARS-CoV-2 (anti-RBD IgG) at five different times and plaque reduction neutralization tests (PRNT) at two different times after vaccination over a period of 18 months. Antibody levels were measured at approximately two-month intervals after the first and second dose, then four months after the third dose, and then one to six months after the fourth dose of vaccine. PRNT was performed two months after the second and four months after the third dose of vaccine. We classified patients into four groups according to the number of vaccine doses and presence of COVID-19 infection. Severe infection was defined as hospital admission for greater than or equal to two weeks or death. There was no difference in antibody levels between naïve and infected patients except after a fourth vaccination, which was effective for increasing antibodies in infection-naïve patients. Age, sex, body mass index (BMI), dialysis vintage, and presence of diabetes mellitus (DM) did not show a significant correlation with antibody levels. Four patients who experienced severe COVID-19 disease tended to have lower antibody levels prior to infection. A fourth dose of SARS-CoV-2 vaccine significantly elevated antibodies in infection-naïve HD patients and may be beneficial for HD patients who have not been previously infected with SARS-CoV-2 for protection against severe infection.

Sphingolipids inhibit endosomal recycling of nutrient transporters by inactivating ARF6.

Endogenous sphingolipids (ceramide) and related synthetic molecules (FTY720, SH-BC-893) reduce nutrient access by decreasing cell surface expression of a subset of nutrient transporter proteins. Here, we report that these sphingolipids disrupt endocytic recycling by inactivating the small GTPase ARF6. Consistent with reported roles for ARF6 in maintaining the tubular recycling endosome, MICAL-L1-positive tubules were lost from sphingolipid-treated cells. We propose that ARF6 inactivation may occur downstream of PP2A activation since: (1) sphingolipids that fail to activate PP2A did not reduce ARF6-GTP levels; (2) a structurally unrelated PP2A activator disrupted tubular recycling endosome morphology and transporter localization; and (3) overexpression of a phosphomimetic mutant of the ARF6 GEF GRP1 prevented nutrient transporter loss. ARF6 inhibition alone was not toxic; however, the ARF6 inhibitors SecinH3 and NAV2729 dramatically enhanced the killing of cancer cells by SH-BC-893 without increasing toxicity to peripheral blood mononuclear cells, suggesting that ARF6 inactivation contributes to the anti-neoplastic actions of sphingolipids. Taken together, these studies provide mechanistic insight into how ceramide and sphingolipid-like molecules limit nutrient access and suppress tumor cell growth and survival.