Dialysate White Blood Cell Change after Initial Antibiotic Treatment Represented the Patterns of Response in Peritoneal Dialysis-Related Peritonitis

Background. Patients with peritoneal dialysis-related peritonitis usually have different responses to initial antibiotic treatment. This study aimed to explore the patterns of response by using the changes of dialysate white blood cell count on the first five days of the initial antibiotic treatment. Materials and Methods. A retrospective cohort study was conducted. All peritoneal dialysis-related peritonitis episodes from January 2014 to December 2015 were reviewed. We categorized the patterns of antibiotic response into 3 groups: early response, delayed response, and failure group. The changes of dialysate white blood cell count for each pattern were determined by multilevel regression analysis. Results. There were 644 episodes in 455 patients: 378 (58.7%) of early response, 122 (18.9%) of delayed response, and 144 (22.3%) of failure episodes. The patterns of early, delayed, and failure groups were represented by the average rate reduction per day of dialysate WBC of 68.4%, 34.0%, and 14.2%, respectively (p value < 0.001 for all comparisons). Conclusion. Three patterns, which were categorized by types of responses, have variable rates of WBC declining. Clinicians should focus on the delayed response and failure patterns in order to make a decision whether to continue medical therapies or to aggressively remove the peritoneal catheter

Multiple extracellular vesicle types in peritoneal dialysis effluent are prominent and contain known biomarkers

Peritoneal dialysis inevitability results in activation of inflammatory processes and its efficiency is highly variable between patients. An improved method to isolate biomarkers and study pathophysiological mechanisms in peritoneal dialysis effluent (PDE) is expected to be of much benefit for the development of this treatment approach and help with patient management. Extracellular vesicles (EVs) are released as part of normal cellular processes. Their proteome is expected to reflect both type and health of their cell of origin. Although there is a significant interest in using EVs for "liquid biopsies", little is reported of their presence or composition in plentiful dialysis waste fluids, including peritoneal dialysis effluent (PDE). Here we determined the presence of EVs in PDE and subsequently characterized their proteome. EVs were first isolated from PDE using differential centrifugation, then a further enrichment using size exclusion chromatography (SEC) was performed. The presence of EVs was demonstrated using transmission electron microscopy, and their particle counts were investigated using nanoparticle tracking analysis and dynamic light scattering. Using tandem mass spectrometry, marker proteins from three types of EVs i.e. apoptotic bodies, ectosomes, and exosomes were identified. The proteomic results demonstrated that the isolation of EVs by differential centrifugation helped enrich for over 2,000 proteins normally masked by abundant proteins in PDE such as albumin and SEC markedly further improved the isolation of low abundant proteins. Gene ontology analysis of all identified proteins showed the marked enrichment of exosome and membrane-associated proteins. Over 3,700 proteins were identified in total, including many proteins with known roles in peritoneal pathophysiology. This study demonstrated the prominence of EVs in PDE and their potential value as a source of biomarkers for peritoneal dialysis patients

Durability of Humoral and Cellular Immunity after an Extended Primary Series with Heterologous Inactivated SARS-CoV-2 Prime-Boost and ChAdOx1 nCoV-19 in Dialysis Patients (ICON3)

The durability of a three-dose extended primary series of COVID-19 vaccine in dialysis patients remains unknown. Here, we assessed dynamic changes in SARS-CoV-2-specific humoral and cell-mediated immunity at baseline, 3 months, and 6 months after the extended primary series in 29 hemodialyzed (HD), 28 peritoneal dialyzed (PD) patients, and 14 healthy controls. Participants received two doses of inactivated SARS-CoV-2 vaccine followed by a dose of ChAdOx1 nCoV-19 vaccine. At 6 months, median anti-RBD IgG titers (IQR) significantly declined from baseline in the HD (1741 (1136–3083) BAU/mL vs. 373 (188–607) BAU/mL) and PD (1093 (617–1911) BAU/mL vs. 180 (126–320) BAU/mL) groups, as did the mean percent inhibition of neutralizing antibodies (HD: 96% vs. 81%; PD: 95% vs. 73%) (all p < 0.01). Age and post-vaccination serological response intensity were predictors of early humoral seroprotection loss. In contrast, cell-mediated immunity remained unchanged. In conclusion, humoral immunity declined substantially in dialysis patients, while cell-mediated immunity remained stable 6 months after the extended heterologous primary series of two inactivated SARS-CoV-2/ChAdOx1 nCoV-19 vaccine. A booster dose could be considered in dialysis patients 3 months after this unique regimen, particularly in the elderly or those with a modest initial humoral response

Apoptotic body, ectosome, and exosome vesicle markers identified in low-density membrane pellets.

<p>Apoptotic body, ectosome, and exosome vesicle markers identified in low-density membrane pellets.</p

Transmission electron micrograph photos of 110,000 x g_ave pellet after size exclusion chromatography (SEC) (A-E) and without SEC (F).

<p>SEC pooled fraction 1–5 showed only grid background (A). SEC pooled fraction 6–10, vesicles (arrowhead) were in very high number and easily identified (B, D). Some other elongated membrane fragments (#) and unidentified large round particles (*) of approximately 250–500 nm were also observed in this fraction albeit very infrequent (E). SEC pooled fraction 11–30, small round particles less than 30 nm without visible membranes were observed under high background level (C). Low-density membrane pellet from non-SEC method had prominent background protein aggregates and other non-vesicle membrane particles mixed with vesicles (F).</p

Gene ontology cell component analysis of proteins enriched by SEC.

<p>The protein list from the pooled low-density membrane pellet sample further purified by SEC compared with the protein list from the same sample without performing SEC showed a significant enrichment of membrane and vesicle terms, especially exosome. The analysis was performed using Gorilla.</p

Patient demographic data.

<p>Patient demographic data.</p

Proteins related to peritoneal membrane injury, fibrosis, and ultrafiltration found in low-density membrane pellet samples.

<p>Proteins related to peritoneal membrane injury, fibrosis, and ultrafiltration found in low-density membrane pellet samples.</p

Particle size analysis.

<p>Particle size distribution was analyzed by nanoparticle tracking analysis (solid line) compared with dynamic light scattering analysis (dashed line).</p

Intraperitoneal cefepime monotherapy versus combination therapy of cefazolin plus ceftazidime for empirical treatment of CAPD-associated peritonitis: A multicenter, open-label, noninferiority, randomized, controlled trial

Rationale & Objective: Compared to combination therapy, intraperitoneal (IP) cefepime monotherapy for continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis may provide potential benefits in lowering staff burden, shortening time-consuming antibiotic preparation, and reducing bag contamination risk. This study sought to evaluate whether cefepime monotherapy is noninferior to combination regimens. Study Design: Multicenter, open-label, noninferiority, randomized, controlled trial. Setting & Participants: Adult incident peritoneal dialysis (PD) patients with CAPD-associated peritonitis in 8 PD centers in Thailand. Interventions: Random assignment to either IP monotherapy of cefepime, 1 g/d, or IP combination of cefazolin and ceftazidime, 1 g/d, both given as continuous dosing. Outcomes: Primary end point: resolution of peritonitis at day 10 (primary treatment response). Secondary outcomes: initial response (day 5), complete cure (relapse/recurrence-free response 28 days after treatment completion), relapsing/recurrent peritonitis, and death from any cause. Noninferiority would be confirmed for the primary outcome if the lower margin of the 1-sided 95% CI was not less than −10% for difference in the primary response rate. A 2-sided 90% CI was used to demonstrate the upper or lower border of the 1-sided 95% CI. Results: There were 144 eligible patients with CAPD-associated peritonitis, of whom 70 and 74 patients were in the monotherapy and combination-therapy groups, respectively. Baseline demographic and clinical characteristics were not different between the groups. The primary response was 82.6% in the monotherapy group and 81.1% in the combination-therapy group (treatment difference, 1.5%; 90% CI, −9.1% to 12.1%; P = 0.04). There was no significant difference in the monotherapy group compared with the combination-therapy group in terms of initial response rate (65.7% vs 60.8%; treatment difference, 4.9%; 95% CI, −10.8% to 20.6%; P = 0.5) and complete cure rate (80.0% vs 80.6%; treatment difference, −0.6%; 95% CI, −13.9% to 12.8%; P = 0.7). Relapsing and recurrent peritonitis occurred in 4.6% and 4.6% of the monotherapy group and 4.2% and 5.6% of the combination-therapy group (P = 0.9 and P = 0.8, respectively). There was nominally higher all-cause mortality in the monotherapy group (7.1% vs 2.7%; treatment difference, 4.4%; 95% CI, −2.6% to 11.5%), but this difference was not statistically significant (P = 0.2). Limitation: Not double blind. Conclusions: IP cefepime monotherapy was noninferior to conventional combination therapy for resolution of CAPD-associated peritonitis at day 10 and may be a reasonable alternative first-line treatment. Funding: This study is supported by The Kidney Foundation of Thailand (R5879), Thailand; Rachadaphiseksompotch Fund (RA56/006) and Rachadaphicseksompotch Endorsement Fund (CU-GRS_61_06_30_01), Chulalongkorn University, Thailand; National Research Council of Thailand (156/2560), Thailand; and Thailand Research Foundation (IRG5780017), Thailand. Trial Registration: Registered at ClinicalTrials.gov with study number NCT02872038