Andreas Vychytil

Background: Peritoneal dialysis (PD) effluent of kidney failure patients represents an accessible liquid biopsy of the peritoneal cavity, yet the mechanisms determining its molecular composition remain poorly understood. We applied an integrative multi-omics approach to characterize the composition, transport dynamics, and molecular origin of the PD effluentome. Methods: Cell-free effluent, effluent cells, and plasma were collected from stable PD patients during standardized peritoneal equilibration tests in a randomized clinical trial. Targeted metabolomics, proteomics, and transcriptomic profiling were integrated with a reference human plasma proteome to investigate temporal molecular changes, peritoneal transport characteristics, and protein origin. Results: A total of 207 metabolites and 2970 proteins were identified in PD effluent. Metabolites exhibited distinct class-specific transport kinetics, with rapid equilibration of amino acids and biogenic amines, whereas lipids remained markedly underrepresented despite prolonged dwell times, indicating that transport is governed by physicochemical properties beyond molecular size alone. The effluent proteome underwent concordant alteration, with dwell time-dependent enrichment of pathways related to extracellular matrix organization, angiogenesis, coagulation, and tissue repair. Integrative analysis of the effluent proteome, effluent-cell transcriptome, and human plasma proteome resolved distinct plasma-associated, effluent cell-associated, resident peritoneal tissue-associated, and mixed-origin protein populations. Conclusions: This study establishes the first systems-level approach describing the composition, transport dynamics, and molecular origin of the PD effluentome. By transforming PD effluent into a biologically interpretable molecular readout of peritoneal membrane biology, this work provides a reference for the mechanistic interpretation of effluent-derived biomarkers and supports future therapeutic monitoring and precision medicine in PD.

Background/Objectives: Peritoneal dialysis (PD) is a renal replacement therapy for patients with kidney failure. Managing PD patients often involves addressing a complex interplay of comorbidities and complications, necessitating the use of multiple medications. This study aimed to systematically characterize commonly co-prescribed drugs in PD and to identify novel drug combinations that may target dysregulated molecular mechanisms associated with PD’s pathophysiology. Methods: We analyzed clinical records from 702 PD patients spanning 30 years, encompassing over 5500 prescription points. Using network-based modeling techniques, we assessed drug co-prescription patterns, clinical outcomes, and longitudinal treatment trends. To explore potential drug repurposing opportunities, we constructed a molecular network model of PD based on a consolidated transcriptomics dataset and integrated this with drug–target interaction information. Results: We found commonly prescribed drugs such as furosemide, sucroferric oxyhydroxide, calcitriol, darbepoetin alfa, and aluminum hydroxide to be integral components of PD patient management, prescribed in over 30% of PD patients. The molecular-network-based approach found combinations of drugs like theophylline, fluoxetine, celecoxib, and amitriptyline to possibly have synergistic effects and to target dysregulated molecules of PD-related pathomechanisms. Two further distinct categories of drugs emerged as particularly interesting in our study: selective serotonin reuptake inhibitors (SSRIs), which were found to modulate molecules implicated in peritoneal fibrosis, and vascular endothelial growth factor (VEGF) inhibitors, which exhibit anti-fibrotic properties that are potentially useful for PD. Conclusions: This comprehensive exploration of drug co-prescriptions in the context of PD-related pathomechanisms provides valuable insights for opening future therapeutic strategies and identifying new targets for drug repurposing.

Background: The global COVID-19 pandemic transformed healthcare services in ways that have impacted individual physical and psychological health. The substantial health challenges routinely faced by dialysis-dependent patients with advanced kidney disease have increased considerably during the ongoing COVID-19 pandemic but remain inadequately investigated. We therefore decided to analyze and compare the perspectives of dialysis patients on their own needs and challenges during the COVID-19 pandemic with those of their professional healthcare providers through interviews with both groups.Methods: Qualitative study of seven in-center hemodialysis patients, seven peritoneal dialysis patients, seven dialysis nurses, and seven physicians at the Medical University of Vienna between March 2020 and February 2021, involving content analysis of semi-structured interviews supported by a natural language processing technique.Results: Among the main themes emerging from interviews with patients were: (1) concerns about being a ‘high-risk patient’; (2) little fear of COVID-19 as a patient on hemodialysis; (3) questions about home dialysis as a better choice than in-center dialysis. Among the main themes brought up by physicians and nurses were: (1) anxiety, sadness, and loneliness of peritoneal dialysis patients; (2) negative impact of changes in clinical routine on patients’ well-being; (3) telehealth as a new modality of care.Conclusion: Preventive measures against COVID-19 (e.g., use of facemasks, distancing, isolation), the introduction of telemedicine, and an increase in home dialysis have led to communication barriers and reduced face-to-face and direct physical contact between healthcare providers and patients. Physicians did not perceive the full extent of patients’ psychological burdens. Selection/modification of dialysis modality should include analysis of the patient’s support network and proactive discussion between dialysis patients and their healthcare providers about implications of the ongoing COVID-19 epidemic. Modification of clinical routine care to increase frequency of psychological evaluation should be considered in anticipation of future surges of COVID-19 or currently unforeseen pandemics.

Anti-SARS-CoV-2 vaccination of dialysis patients has been proven to be safe and effective to reduce COVID-19-related morbidity and mortality. However, data on the durability of anti-SARS-CoV-2 antibodies post-vaccination in peritoneal dialysis (PD) patients are scarce. In this prospective single-center cohort study we measured anti-SARS-CoV-2 RBD antibodies 3 and 6 months after the 3rd dose of the mRNA-1273 vaccine in 27 adult PD patients and recorded breakthrough infections. Furthermore, in a mixed model analysis, we analyzed potential factors influencing the humoral response following vaccination. Anti-SARS-CoV-2 RBD antibody levels declined from 21,424 BAU/mL at 1 month to 8397 BAU/mL at 3 months and to 5120 BAU/mL at 6 months after the 3rd dose, but remained higher than pre-3rd dose levels (212 BAU/mL). Eight patients (29.6%) were infected with SARS-CoV-2 within six months from the 3rd dose during the Omicron wave. Previous high antibody levels, high glomerular filtration rate (GFR) and low Davies Comorbidity Score were associated with higher anti-SARS-CoV-2 antibody levels after the booster. In conclusion, PD patients exhibited a robust and durable humoral response after a third dose of the mRNA-1273 vaccine. A high GFR and low comorbidity as well as previous high antibody levels predicted a better humoral response to vaccination.

ZUSAMMENFASSUNG: Im Jahr 2022 wurden die neuen Leitlinien der International Society for Peritoneal Dialysis (ISPD) zur Diagnostik, Prophylaxe und Therapie der Peritonitis publiziert. Die maximal tolerierbare Peritonitisrate pro Zentrum wurde auf 0,4 Episoden/ Jahr herabgesenkt, wobei weniger als 15 % der Peritonitisfälle kulturnegativ sein sollten. Es wird empfohlen, auch die Peritonitisfälle, die vor Beginn der Peritonealdialyse (PD) auftreten, separat zu analysieren. Eine antibiotische Prophylaxe wird vor Katheterimplantation sowie vor Kolonoskopien und invasiven gynäkologischen Prozeduren empfohlen. Besondere hygienische Maßnahmen sind erforderlich, wenn Haustiere vorhanden sind. Anstelle einer Kombinationstherapie kann zur Abdeckung des gramnegativen und grampositiven Keimspektrums auch eine Monotherapie mit einem Cephalosporin der 4. Generation verwendet werden. Bei Wahl eines Aminoglykosids wird eine additive Therapie mit N-Azetylcystein zur Verhinderung der Ototoxizität empfohlen. Sollte 48 h nach Therapiebeginn keine Besserung eintreten, müssen weitere diagnostische Maßnahmen wie etwa die Abnahme neuerlicher Kulturen und Computertomografie des Abdomens durchgeführt werden.

In dialysis patients the humoral response to anti-SARS-CoV-2 vaccines is attenuated and rapidly declines over time. However, data on the persistence of the immune response in peritoneal dialysis (PD) patients are scarce, particularly after a third (booster) dose with mRNA-1273 vaccine. In this prospective cohort study, we report anti-SARS-CoV-2 antibody levels in PD patients before and after the third dose of mRNA-1273 vaccine. Six months after the second dose, anti-SARS-CoV-2 antibodies were detected in all patients (n = 34). However, within this time period antibodies substantially declined in 31 of 34 patients (4.5-fold, median = 192 BAU/mL, p = 1.27 × 10^–9) and increased in three patients. In accordance with government regulations, a third dose of mRNA-1273 vaccine (50 μg) was given to 27 PD patients 6 months after the second dose which induced a significant increase of anti-SARS-CoV-2 antibody titers (58.6-fold, median = 19405 BAU/mL, p = 1.24 × 10^–29). A mixed model analysis showed that a lower Davies Comorbidity Score and a higher GFR were associated with higher antibody titers (p = 0.03 and p = 0.02). The most common adverse events after the third dose were pain at the injection site (77.8%) and fatigue (51.9%). No hospitalizations were reported. In conclusion, 6 months after the second dose of mRNA-1273 vaccine, anti-SARS-CoV-2 antibodies substantially decreased in PD patients, whereas a well-tolerated third dose induced a robust humoral response. Our data suggest that the administration of a booster dose within a shorter interval than 6 months should be considered in PD patients in order to maintain high anti-SARS-CoV-2 antibody levels and assure protection from severe COVID-19 disease.

New recommendations on evaluation of peritoneal membrane function suggest ruling out catheter dysfunction when evaluating patients with low ultrafiltration capacity. We introduce the use of a combination of parameters obtained from the cycler software PD Link with HomeChoicePro (Baxter International Inc., Illinois, United States) cyclers for predicting catheter dysfunction in automated peritoneal dialysis patients (APD). Out of 117 patients treated at the Medical University of Vienna between 2015 and 2021, we retrospectively identified all patients with verified catheter dysfunction (n = 14) and compared them to controls without clinical evidence of mechanical catheter problems and a recent X-ray confirming PD catheter tip in the rectovesical/rectouterine space (n = 19). All patients had a coiled single-cuff PD catheter, performed tidal PD, and received neutral pH bicarbonate/lactate-buffered PD fluids with low-glucose degradation products on APD. Icodextrin-containing PD fluids were used for daytime dwells. We retrieved cycler data for seven days each and tested parameters' predictive capability of catheter dysfunction. Total number of alarms/week > 7 as single predictive parameter of catheter dislocation identified 85.7% (sensitivity) of patients with dislocated catheter, whereas 31.6% (1-specificity) of control patients were false positive. A combination of parameters (number of alarms/week > 7, total drain time > 22 min, ultrafiltration of last fill < 150 mL) where at least two of three parameters appeared identified the same proportion of patients with catheter dislocation, but was more accurate in identifying controls (21.1% false positive). In contrast to yearly PET measurements, an easily applicable combination of daily cycler readout parameters, also available in new APD systems connected to remote monitoring platforms shows potential for diagnosis of catheter dysfunction during routine follow-up.