Effects of Alanyl-Glutamine Treatment on the Peritoneal Dialysis Effluent Proteome Reveal Pathomechanism-Associated Molecular Signatures.

Peritoneal dialysis (PD) is a modality of renal replacement therapy in which the high volumes of available PD effluent (PDE) represents a rich source of biomarkers for monitoring disease and therapy. Although this information could help guide the management of PD patients, little is known about the potential of PDE to define pathomechanism-associated molecular signatures in PD.We therefore subjected PDE to a high-performance multiplex proteomic analysis after depletion of highly-abundant plasma proteins and enrichment of low-abundance proteins. A combination of label-free and isobaric labeling strategies was applied to PDE samples from PD patients (n = 20) treated in an open-label, randomized, two-period, cross-over clinical trial with standard PD fluid or with a novel PD fluid supplemented with alanyl-glutamine (AlaGln).With this workflow we identified 2506 unique proteins in the PDE proteome, greatly increasing coverage beyond the 171 previously-reported proteins. The proteins identified range from high abundance plasma proteins to low abundance cellular proteins, and are linked to larger numbers of biological processes and pathways, some of which are novel for PDE. Interestingly, proteins linked to membrane remodeling and fibrosis are overrepresented in PDE compared with plasma, whereas the proteins underrepresented in PDE suggest decreases in host defense, immune-competence and response to stress. Treatment with AlaGln-supplemented PD fluid is associated with reduced activity of membrane injury-associated mechanisms and with restoration of biological processes involved in stress responses and host defense.Our study represents the first application of the PDE proteome in a randomized controlled prospective clinical trial of PD. This novel proteomic workflow allowed detection of low abundance biomarkers to define pathomechanism-associated molecular signatures in PD and their alterations by a novel therapeutic intervention.

Exclusion of pregnancy in dialysis patients: diagnostic performance of human chorionic gonadotropin.

BACKGROUND: A positive pregnancy test in acute or chronically ill patients has implications for the use of potentially mutagenic or teratogenic products in urgent medical therapies such as the use of chemotherapies or therapies with immunosuppressants, for anesthesia, and for time-sensitive indications like urgent surgery or organ Transplantation. Despite a lack of evidence, it is currently believed that human chorionic gonadotropin serum concentrations are always elevated in female dialysis patients even without pregnancy. It is also believed that human chorionic gonadotropin cannot be used to confirm or exclude pregnancy. METHODS: Human chorionic gonadotropin was examined in female dialysis patients (18-50 years of age), and was classified as positive above 5 mlU/ml. In addition, fertility status was determined. For an enhanced index test, the cut-off of 5 mIU/ml was used for potentially fertile patients and 14 mIU/ml for infertile patients to calculate diagnostic test accuracy. The ideal cut-off for human chorionic gonadotropin was estimated using Liu's method with bootstrapped 95% confidence intervals. Predictors of human chorionic gonadotropin increase were analyzed using multivariable linear regression. RESULTS: Among 71 women, two (2.8%) were pregnant, 46 (64.8%) potentially fertile, and 23 (32.4%) infertile. We observed human chorionic gonadotropin concentrations > 5 mIU/ml in 10 patients, which had a sensitivity of 100% (95% confidence interval: 100 to 100), a specificity of 86% (95% confidence interval: 77 to 94), a positive predictive value of 17% (95% confidence interval: 8 to 25) and a negative predictive value of 100% (95% confidence interval: 100 to 100) for the diagnosis of pregnancy. Using a cut-off > 14 mIU/ml for infertile patients or the exclusion of infertile patients increased specificity to 93% or 98%, respectively. The ideal cut-off was 25 mIU/ml (95% confidence interval: 17 to 33). Pregnancy and potential fertility, but not age, were independent predictors of human chorionic gonadotropin. CONCLUSION: Human chorionic gonadotropin is elevated > 5mIU/ml in 14.5% of non-pregnant dialysis patients of child-bearing age. In potentially fertile women, this cut-off can be used to exclude pregnancy. In case of an unknown fertility status, the ideal human chorionic gonadotropin cut-off was 25 mIU/ml.

Markers of potassium homeostasis in salt losing tubulopathies- associations with hyperaldosteronism and hypomagnesemia.

BACKGROUND: Renal loss of potassium (K+) and magnesium (Mg2+) in salt losing tubulopathies (SLT) leads to significantly reduced Quality of Life (QoL) and higher risks of cardiac arrhythmia. The normalization of K+ is currently the most widely accepted treatment target, however in even excellently designed RCTs the increase of K+ was only mild and rarely normalized. These findings question the role of K+ as the ideal marker of potassium homeostasis in SLT. Aim of this hypothesis-generating study was to define surrogate endpoints for future treatment trials in SLT in terms of their usefulness to determine QoL and important clinical outcomes. METHODS: Within this prospective cross-sectional study including 11 patients with SLTs we assessed the biochemical, clinical and cardiological parameters and their relationship with QoL (RAND SF-36). The primary hypothesis was that QoL would be more dependent of higher aldosterone concentration, assessed by the transtubular-potassium-gradient (TTKG). Correlations were evaluated using Pearson's correlation coefficient. RESULTS: Included patients were mainly female (82%, mean age 34 ± 12 years). Serum K+ and Mg2+ was 3.3 ± 0.6 mmol/l and 0.7 ± 0.1 mmol/l (mean ± SD). TTKG was 9.5/3.4-20.2 (median/range). While dimensions of mental health mostly correlated with serum Mg2+ (r = 0.68, p = 0.04) and K+ (r = 0.55, p = 0.08), better physical health was associated with lower aldosterone levels (r = -0.61, p = 0.06). TTKG was neither associated with aldosterone levels nor with QoL parameters. No relevant abnormalities were observed in neither 24 h-ECG nor echocardiography. CONCLUSIONS: Hyperaldosteronism, K+ and Mg2+ were the most important parameters of QoL. TTKG was no suitable marker for hyperaldosteronism or QoL. Future confirmatory studies in SLT should assess QoL as well as aldosterone, K+ and Mg2+.

A randomized controlled trial of alanyl-glutamine supplementation in peritoneal dialysis fluid to assess impact on biomarkers of peritoneal health.

In early clinical testing, acute addition of alanyl-glutamine (AlaGln) to glucose-based peritoneal dialysis (PD) fluids restored peritoneal cellular stress responses and leukocyte function. This study was designed to test the effect of extended treatment with AlaGln-supplemented PD fluid on biomarkers of peritoneal health. In a double-blinded, randomized crossover design, stable PD patients were treated with AlaGln (8 mM) or placebo added to PD fluid for eight weeks. As primary outcome measures, dialysate cancer-antigen 125 (CA-125) appearance rate and ex vivo stimulated interleukin-6 (IL-6) release were assessed in peritoneal equilibration tests. In 8 Austrian centers, 54 patients were screened, 50 randomized, and 41 included in the full analysis set. AlaGln supplementation significantly increased CA-125 appearance rate and ex vivo stimulated IL-6 release. AlaGln supplementation also reduced peritoneal protein loss, increased ex vivo stimulated tumor necrosis factor (TNF)-α release, and reduced systemic IL-8 levels. No adverse safety signals were observed. All 4 peritonitis episodes occurred during standard PD fluid treatment. A novel AlaGln-supplemented PD fluid improves biomarkers of peritoneal membrane integrity, immune competence, and systemic inflammation compared to unsupplemented PD fluid with neutral pH and low-glucose degradation. A phase 3 trial is needed to determine the impact of AlaGln supplementation on hard clinical outcomes.

Low-Sodium Versus Standard-Sodium Peritoneal Dialysis Solution in Hypertensive Patients: A Randomized Controlled Trial.

BACKGROUND: Peritoneal dialysis (PD) solutions with reduced sodium content may have advantages for hypertensive patients; however, they have lower osmolarity and solvent drag, so the achieved Kt/Vurea may be lower. Furthermore, the increased transperitoneal membrane sodium gradient can influence sodium balance with consequences for blood pressure (BP) control. STUDY DESIGN: Prospective, randomized, double-blind clinical trial to prove the noninferiority of total weekly Kt/Vurea with low-sodium versus standard-sodium PD solution, with the lower confidence limit above the clinically accepted difference of -0.5. SETTING & PARTICIPANTS: Hypertensive patients (≥ 1 antihypertensive drug, including diuretics, or office systolic BP ≥ 130 mmHg) on continuous ambulatory PD therapy from 17 sites. INTERVENTION: 108 patients were randomly assigned (1:1) to 6-month treatments with either low-sodium (125 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 338-491 mOsm/L) or standard-sodium (134 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 356-509 mOsm/L) PD solution. OUTCOMES: Primary end point: weekly total Kt/Vurea; secondary outcomes: BP control, safety, and tolerability. MEASUREMENTS: Total Kt/Vurea was determined from 24-hour dialysate and urine collection; BP, by office measurement. RESULTS: Total Kt/Vurea after 12 weeks was 2.53 ± 0.89 in the low-sodium group (n = 40) and 2.97 ± 1.58 in the control group (n = 42). The noninferiority of total Kt/Vurea could not be confirmed. There was no difference for peritoneal Kt/Vurea (1.70 ± 0.38 with low sodium, 1.77 ± 0.44 with standard sodium), but there was a difference in renal Kt/Vurea (0.83 ± 0.80 with low sodium, 1.20 ± 1.54 with standard sodium). Mean daily sodium removal with dialysate at week 12 was 1.188 g higher in the low-sodium group (P < 0.001). BP changed marginally with standard-sodium solution, but decreased with low-sodium PD solution, resulting in less antihypertensive medication. LIMITATIONS: Broader variability of study population than anticipated, particularly regarding residual kidney function. CONCLUSIONS: The noninferiority of the low-sodium PD solution for total Kt/Vurea could not be proved; however, it showed beneficial clinical effects on sodium removal and BP.

Dynamic O-linked N-acetylglucosamine modification of proteins affects stress responses and survival of mesothelial cells exposed to peritoneal dialysis fluids.

The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. Viability was decreased by reducing O-GlcNAc levels by DON, which also led to suppressed expression of the cytoprotective heat shock protein 72. In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. Addition of alanyl-glutamine increased O-GlcNAcylation and partly counteracted its inhibition by DON, also leading to improved cell survival. Immunofluorescent analysis of clinical samples showed that the O-GlcNAc signal primarily originates from mesothelial cells. In conclusion, this study identified O-GlcNAcylation in mesothelial cells as a potentially important molecular mechanism after exposure to PDF. Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD.

Use of sodium thiosulphate in a multi-interventional setting for the treatment of calciphylaxis in dialysis patients.

BACKGROUND: Calciphylaxis is a life-threatening complication in patients with end-stage renal disease (ESRD). No established therapy exists so far. The aim of the present study was to determine the therapeutic response to a multi-interventional treatment regimen with consistent use of sodium thiosulphate (STS) in an Austrian cohort of calciphylaxis patients. METHODS: We retrospectively collected demographic, clinical and laboratory data on 27 calciphylaxis patients treated with STS at seven Austrian dialysis centres between June 2004 and November 2010. RESULTS: Twenty-seven dialysis patients (68 ± 12 years) were treated with STS for a median (25th, 75th percentile) of 96 (54, 133) days. Seven patients (26%) suffered from proximal-type, and 20 patients (74%) from distal-type calciphylaxis. Fourteen patients (52%) showed a complete remission, five patients (19%) a partial remission and eight patients (30%) progression that resulted in amputation in four patients. During a median follow-up of 101 (79, 273) days, 14 patients died (52%). Non-survivors were older (P = 0.04), showed higher CRP values (P = 0.04), presented more frequently with proximal-type calciphylaxis (P = 0.03), had a higher disease severity score at diagnosis (P = 0.01), were treated more often with antibiotics (P = 0.01) and cinacalcet (P = 0.03) and had a lower remission rate during treatment (P = 0.004) than did survivors. The use of antibiotics and cinacalcet, disease severity at diagnosis and remission rates were found to be significant survival predictors in logistic regression analysis. CONCLUSIONS: Calciphylaxis remains a serious complication with high mortality. Early and consistent therapy including STS may help to improve the disease outcome.

Comparative in vitro fungicidal activity of echinocandins against Candida albicans in peritoneal dialysis fluids.

The peritoneal dialysis (PD)-associated peritonitis caused by fungi is a relatively rare, but very serious disease. PD fluids (PDFs) affect inhibitory efficacy on the microorganisms' growth, which may compromise the affectivity of some antimicrobials. The purpose of this study was to investigate in vitro the fungicidal effectiveness of echinocandins in diverse PDFs. The fungicidal efficacy of caspofungin (CAS), anidulafungin (ANA), micafungin (MYC) against five clinical isolates of Candida albicans was studied in the different PDFs using time-kill curves. As control substance amphotericin B was used. Echinocandins showed slower and reduced killing of C. albicans in PDFs when compared with the time-kill curves in control bouillon. At concentration of 8 × minimal inhibitory concentration (MIC) the greatest reduction in the growth of C. albicans was seen by ANA in lactate-buffered Nutrineal PD4(®) with 1.1% amino acid (2.33 ± 0.52 log10 CFU ml(-1) ), and by CAS and MYC in lactate-buffered Dianeal PD4(®) with 1.36% glucose (2.36 ± 0.89 log10 CFU ml(-1) and 2.36 ± 0.99 log10 CFU ml(-1) respectively). Using high concentration of 128 × MIC echinocandins achieved fungicidal effect in all PDFs. PDFs may significantly impair the activities of echinocandins, but fungicidal activity of drugs can be achieved at high concentration of 128 × MIC.

[Peritoneal dialysis from the beginnings up to today: which developments of the last decades were important?]. / Peritonealdialyse gestern und heute: welche Entwicklungen und Erkenntnisse waren in den letzten Jahrzehnten bedeutend?

During the past years new developments in peritoneal dialysis (PD) technique have resulted in continuous improvement of patient outcome. The importance of salt and fluid balance, residual renal function and peritoneal glucose load are of increasing interest, whereas small solute clearances have lost importance. In patients with high peritoneal transport rates automated PD (APD) is indicated. However, APD can also be chosen as initial PD treatment since recent studies show comparable or even better survival as compared to continuous ambulatory PD patients. Alternative PD solutions improve peritoneal ultrafiltration (icodextrin), reduce peritoneal glucose load (amino acid solution, icodextrin) and protect the peritoneal membrane (solutions with low concentration of glucose degradation products). Infection risk can be reduced when using antibiotic creams, but resistances should be considered. Ongoing studies will clarify if non-antibiotic agents, e.g. medihoney, are effective in preventing PD-associated infections. Due to these improvements PD and hemodialysis have become equivalent treatments.

Challenges to dialysis treatment during the COVID-19 pandemic: a qualitative study of patients' and experts' perspectives.

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.

Durable Anti-SARS-CoV-2 Antibody Response after mRNA-1273 Booster in Peritoneal Dialysis Patients during the Omicron Wave.

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.

Plasma and intraperitoneal pharmacokinetics of ceftazidime/avibactam in peritoneal dialysis patients.

OBJECTIVES: Peritonitis is a serious complication in patients undergoing automated peritoneal dialysis (APD) that increases morbidity and frequently disqualifies patients from the peritoneal dialysis programme. Ceftazidime/avibactam (CAZ/AVI) is a potential treatment option for APD patients with peritonitis caused by resistant Gram-negative bacteria, but limited data exist on systemic and target-site pharmacokinetics (PK) in patients undergoing APD. This study set out to investigate the PK of CAZ/AVI in plasma and peritoneal dialysate (PDS) of patients undergoing APD. METHODS: A prospective, open-label PK study was conducted on eight patients undergoing APD. CAZ/AVI was administered as a single intravenous dose of 2 g/0.5 g over 120 minutes. APD cycles were initiated 15 hours after the study drug administration. Dense PDS and plasma sampling was performed for 24 hours after the start of administration. PK parameters were analysed with population PK modelling. Probability of target attainment (PTA) was simulated for different CAZ/AVI doses. RESULTS: PK profiles of both drugs in plasma and PDS were similar, indicating that the two drugs are well suited for a fixed-dose combination. A two-compartment model best described the PK of both drugs. A single dose of 2 g/0.5 g CAZ/AVI led to concentrations that far exceeded the PK/PD targets of both drugs. In the Monte Carlo simulations, even the lowest dose (750/190 mg CAZ/AVI) achieved a PTA of >90% for MICs up to 8 mg/L (The European Committee on Antimicrobial Susceptibility Testing epidemiological cut-off value for Pseudomonas aeruginosa) in plasma and PDS. DISCUSSION: On the basis of PTA simulations, a dose of 750/190 mg CAZ/AVI would be sufficient to treat plasma and peritoneal fluid infections in patients undergoing APD.

Pharmacokinetics of intraperitoneal and intravenous fosfomycin in automated peritoneal dialysis patients without peritonitis.

Blood and dialysate concentrations of fosfomycin were determined after intravenous and intraperitoneal application of 4 mg/liter in patients undergoing automated peritoneal dialysis. Maximum serum concentrations after intravenous (287.75 ± 86.34 mg/liter) and intraperitoneal (205.78 ± 66.78 mg/liter) administration were comparable. Ratios of intraperitoneal to systemic exposure were 1.12 (intraperitoneal administration) and 0.22 (intravenous administration), indicating good systemic exposure after intraperitoneal application but limited penetration of fosfomycin into the peritoneal fluid after the intravenous dose.

Rapid T-cell-based immunodiagnosis of tuberculous peritonitis in a peritoneal dialysis patient.

Tuberculous peritonitis is a rare complication during peritoneal dialysis (PD). This report presents the case of a patient with clinical signs and symptoms indicative of bacterial peritonitis, but without culture growth of conventional bacteria or fungi. Cytokine flow cytometry after overnight stimulation of cells from peripheral blood and the peritoneal dialysate with Mycobacterium tuberculosis (MTB)-specific antigens revealed a 40-fold increase in MTB-specific CD4 + T cells expressing interferon-γ (IFN-γ) in peritoneal fluid compared with blood, which was indicative of active tuberculosis (TB). The presence of TB was later confirmed by polymerase chain reaction and growth of MTB in culture of the dialysate. The case illustrates the usefulness of MTB-specific immunodiagnosis for the rapid identification of peritoneal TB in PD patients.

Humoral Response to mRNA-1273 SARS-CoV-2 Vaccine in Peritoneal Dialysis Patients: Is Boostering After Six Months Adequate?

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.

Assessing mechanical catheter dysfunction in automated tidal peritoneal dialysis using cycler software: a case control, proof-of-concept study.

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.

SARS-CoV-2 IgG spike protein antibody response in mRNA-1273 Moderna® vaccinated patients on maintenance immunoapheresis - a cohort study.

Background: The SARS-CoV-2 pandemic increased mortality and morbidity among immunocompromised populations. Vaccination is the most important preventive measure, however, its effectiveness among patients depending on maintenance immunoglobulin G (IgG) apheresis to control autoimmune disease activity is unknown. We aimed to examine the humoral immune response after mRNA-1273 Moderna® vaccination in immunoapheresis patients. Methods: We prospectively monitored SARS-CoV-2 IgG spike (S) protein antibody levels before and after each IgG (exposure) or lipid (LDL) apheresis (controls) over 12 weeks and once after 24 weeks. Primary outcome was the difference of change of SARS-CoV-2 IgG S antibody levels from vaccination until week 12, secondary outcome was the difference of change of SARS-CoV-2 IgG S antibody levels by apheresis treatments across groups. Results: We included 6 IgG and 18 LDL apheresis patients. After 12 weeks the median SARS-CoV-2 IgG S antibody level was 115 (IQR: 0.74, 258) in the IgG and 1216 (IQR: 788, 2178) in the LDL group (p=0.03). Median SARS-CoV-2 IgG S antibody reduction by apheresis was 76.4 vs. 23.7% in the IgG and LDL group (p=0.04). The average post- vs. pre-treatment SARS-CoV-2 IgG S antibody rebound in the IgG group vs. the LDL group was 46.1 and 6.44%/week from prior until week 12 visit. Conclusions: IgG apheresis patients had lower SARS-CoV-2 IgG S antibody levels compared to LDL apheresis patients, but recovered appropriately between treatment sessions. We believe that IgG apheresis itself probably has less effect on maintaining the immune response compared to concomitant immunosuppressive drugs. Immunization is recommended independent of apheresis treatment.

Managing Hospitalized Peritoneal Dialysis Patients: Ten Practical Points for Non-Nephrologists.

Although nephrologists are responsible for the long-term care of dialysis patients, physicians from all disciplines will potentially be involved in the management of patients with kidney failure, including patients on peritoneal dialysis, the major home-based form of kidney-replacement therapy. This review aims to fill knowledge gaps of non-experts in peritoneal dialysis and to highlight key management aspects of in-hospital care of patients on peritoneal dialysis, with a focus on acute scenarios to facilitate prompt decision-making. The clinical pearls provided should enable non-nephrologists to avoid common pitfalls in the initial assessment of peritoneal dialysis-related complications and guide their decision regarding when to refer their patients to a specialist, resulting in improved multidisciplinary patient care.

Antibody Response and Safety After mRNA-1273 SARS-CoV-2 Vaccination in Peritoneal Dialysis Patients - the Vienna Cohort.

Background: Dialysis patients are at high risk for a severe clinical course after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Safety and early immune responses after mRNA-based vaccination have been reported mostly in patients on hemodialysis (HD), whereas reports of peritoneal dialysis (PD) patients remain rare. Methods: In this retrospective observational study, 39 PD patients had received two doses of the mRNA-1273 Moderna® vaccine. We analyzed SARS-CoV-2 Spike (S) antibody titers 4 weeks after each dose of mRNA-1273 and report local and systemic side effects in PD patients that occurred within one week after each mRNA-1273 dose. Using a quantile regression model we examined factors that might influence SARS-CoV-2 S antibody levels in PD patients. Results: Four weeks after the first dose of mRNA-1273 vaccine 33 of 39 (84.6%) PD patients seroconverted and presented with 6.62 U/mL (median; IQR 1.57-22.5) anti-SARS-CoV-2 S antibody titers. After the second dose, 38 of 39 (97.4%) PD patients developed anti-SARS-CoV-2 S antibodies and titers increased significantly (median 968 U/mL; IQR 422.5-2500). Pain at the injection site was the most common local adverse event (AE) (71%). Systemic AEs occurring after the first dose were mostly fatigue (33%) and headache (20%). No severe systemic AEs were reported after the first injection. After the second dose the incidence and the severity of the systemic AEs increased. The most common systemic AEs were: fatigue (40.5%), headache (22.5%), joint pain (20%), myalgia (17.5%) and fever (13%). Lower Davies Comorbidity Score (p=0.04) and shorter dialysis vintage (p=0.017) were associated with higher antibody titers after the first dose. Patients with higher antibody titers after the first dose tended to have higher antibody titers after the second dose (p=1.53x10-05). Conclusions: Peritoneal dialysis patients in this cohort had a high seroconversion rate of 97.4%, showed high antibody titers after full vaccination and tolerated the anti-SARS-CoV-2 mRNA-1273 vaccine well without serious adverse events.

Microstructural comparative analysis of calcification patterns in calciphylaxis versus arteriolosclerotic ulcer of Martorell.

BACKGROUND: Calciphylaxis and the arteriolosclerotic ulcer of Martorell (ASUM) represent two entities of cutaneous calcific arteriolopathies. Their differential diagnosis can be challenging, given similarities in their clinical and histological presentation. Calcification patterns have been proposed as a possible discriminative histological criterion, however, a systematic microstructural comparative analysis is lacking. OBJECTIVES: The study aimed at a systematic comparative microstructural analysis of the calcification patterns in calciphylaxis versus ASUM. MATERIALS & METHODS: Skin biopsies of patients with leg ulcers due to calciphylaxis (20) and ASUM (69) diagnosed at three European wound care centres (Vienna, Bern, Zurich) were included. The extent of calcification, arteriolar calcification pattern and presence of extra-arteriolar calcification were assessed. RESULTS: All calciphylaxis and most ASUM patients (77%) presented with arteriolar calcification. Although the mean number of calcified vessels and the proportion of calcified area were significantly higher in calciphylaxis specimens (p = 0.003 and p = 0.0171), there was no significant difference in the pattern of arteriolar calcification (p = 0.177). Interestingly, extra-arteriolar calcification was detected in the majority of both calciphylaxis (93.3%) and ASUM samples (85.2%, p = 0.639). Notably, Alizarin Red S staining was superior to H&E for the detection of calcifications of both entities (p = 0.014 and p < 0.0001), and to von Kossa staining for ASUM samples (p = 0.0001). However, no differences could be observed between cases with uraemic and non-uraemic calciphylaxis or ulcerations located on the upper and lower leg. CONCLUSION: Our results indicate that extra-arteriolar calcification is not only present in calciphylaxis, but can also be detected in ASUM suggesting a lack of specificity for this finding. However, more specific calcification stains, such as Alizarin Red S, should be used in suspected cases, as calcifications may be overlooked using conventional H&E staining.