Peritoneal Effluent Research Articles

Profiling cytokines in peritoneal effluent through a targeted multiplex cytokine panel provides novel insight into the localized proinflammatory processes in patients undergoing peritoneal dialysis.

The number of relevant markers indicating local intraperitoneal inflammation in patients undergoing peritoneal dialysis (PD) is limited. Therefore, this study aimed to evaluate the compatibility of peritoneal effluent (PE) for proteomic analysis and assess its potential utility in immunoprofiling studies. This pilot study included six PD patients from the Peritoneal Dialysis Center, Department of Nephrology, Transplantology, and Internal Medicine in Szczecin, Poland. All patients were clinically stable, with no signs of infections or malignancy at the time of study. PE samples were collected during routine surveillance visits at the Peritoneal Dialysis Center. Proteomic analysis of the samples was conducted using the Olink® (Olink Proteomics AB, Uppsala, Sweden) Target 48 Cytokine panel. PE samples were successfully analyzed, with 28 out of 45 proteins found within the limit of quantitation (LOQ) and 32 out of 45 proteins detected above the limit of detection (LOD). No significant interference from the matrix was observed in the assay. Biomarkers associated with low-grade inflammation showed varied levels, and the observed patterns were comparable across all patients. This study suggests that utilizing a cytokine panel with relative quantification is a promising method for PE immunoprofiling.

Intraperitoneal MASP-1 Levels are Associated with Peritoneal Solute Transport Rate in Peritoneal Dialysis Patients: A Retrospective Cohort Study.

A major limitation of long-term peritoneal dialysis (PD) is peritoneal membrane dysfunction characterized by faster peritoneal solute-transport rate (PSTR). This study aimed to identify efficient complement factors in peritoneal effluents of continuous ambulatory peritoneal dialysis (CAPD) patients that can predict the PSTR. A multiplex suspension protein array was used to screened related complement pathways in overnight peritoneal effluents among 58 CAPD patients. Then the related complement factors in lectin and classical pathways in effluents were analyzed using ELISA kits among another cohort of 129 CAPD patients. Logistic regression modeling was fitted to predict the PSTR of PD patients. The multiplex suspension protein array showed complement factors including C2, C4b, C5, C5a, Factor D, Factor I, and MBL were detected in effluents of CAPD patients, and the effluent C2 Appearance rate (Ar) and C4b Ar levels were significantly correlated with D/P Cr and D/D0 glucose. The levels of effluents MASP-1 Ar, M-Ficolin Ar, C2 Ar and C4b Ar, which belong to the lectin pathway were also positively correlated with D/P Cr according the ELISA results and these parameters were expressed higher in the high and high-average (H/HA) groups according to the PET results. Moreover, effluent Masp-1 was independently associated with increased PSTR and adverseevents relatedperitonealtransportfunction failure. This study suggested that the lectin pathway may be involvedin local complement activation and peritoneal injury of PD patients, intraperitoneal level of Masp-1 was an independent predictor of increased PSTR in PD patients.

Intraperitoneally Administered Vancomycin Results in Suboptimal Serum and Peritoneal Effluent Drug Levels in Patients with PD-related Peritonitis

Background Intraperitoneal vancomycin is commonly used to treat peritoneal dialysis (PD)-related peritonitis. Therapeutic drug level monitoring helps optimize the use of vancomycin in CKD patients. We studied whether sufficient serum levels were achieved in patients with PD-related peritonitis treated with the commonly used dose of vancomycin in patients with end stage renal disease. Materials and Methods All consecutive patients with PD-related peritonitis during 19 months were studied. Patients received IP Vancomycin 15 mg/kg Q96H and amikacin 2 mg/kg while awaiting culture reports. Vancomycin concentration in serum and dialysate was determined by a validated liquid chromatography-tandem mass spectrometry assay at 1, 12, 24, and 96 h. The primary outcome was the drug levels in serum and peritoneal fluid, and the secondary outcome was peritonitis treatment failure. Results A total of 45 episodes of PD-related peritonitis were treated, of which 41 fulfilled the inclusion criteria and were included in the PK analysis. Recommended serum vancomycin trough level of >15 mg/L was achieved in only two cases. Twenty-one episodes required catheter removal. Conclusion In patients with PD-related peritonitis, intermittent intraperitoneal administration of 15 mg/kg of vancomycin every 96 h does not achieve the recommended serum and dialysate levels of vancomycin. There is an urgent need for pharmacokinetic studies on commonly used IP antibiotics in the PD population to facilitate correct dose recommendations.

An investigation into the correlation between intraperitoneal teicoplanin concentrations and treatment outcomes in peritoneal dialysis-associated peritonitis.

Peritoneal dialysis-associated peritonitis (PDAP) is a frequent complication of peritoneal dialysis. The guidelines from the International Society for Peritoneal Dialysis (ISPD) suggest administering teicoplanin through the peritoneal route to treat PDAP, but do not specify the ideal concentration for peritoneal dialysis effluent (PDE). Patients meeting the trial criteria for PDAP in our hospital between July 2022 and December 2023 were enrolled. Data on PDE white blood cell count, PDE neutrophil percentage, clinical symptoms, CRP, and PCT were gathered pre- and post-treatment. Incidences of adverse drug reaction (ADR) and case numbers during treatment were recorded. Subsequently, patients were categorized into cured and uncured groups for evaluating the relationship between PDE teicoplanin concentration and treatment effectiveness. The self-control study results on teicoplanin efficacy indicated intraperitoneal teicoplanin administration achieved an efficacy rate of 88.9% and an ADR incidence of 5.5% in treating PDAP patients. There was no observed correlation between teicoplanin blood concentration and PDE concentration. PDE teicoplanin concentrations on days 1, 3, 5, and 7 post-dosing were higher inthe cured group, with a significant contrast in PDE concentration on day 5 between the 18.98 ± 2.43mg/L of the cured group and the 12.07 ± 2.68mg/L of the uncured group. ROC curve revealed a higher likelihood of cure in patients when PDE teicoplanin concentration exceeded 15.138mg/L on day 5 post-dosing. Univariate and multifactorial studies identified 24-h urine volume and the number of daily abdominal dialysis sessions as influential factors in PDE teicoplanin concentration on day 5. A positive correlation was found between 24-h urine volume and PDE teicoplanin concentration, with PDAP patients having urine volume over 537mL showing significantly higher drug concentrations. Conversely, the number of daily PDAP sessions was negatively correlated with PDE teicoplanin concentrations, indicating that patients with 1∼3 daily PDAP sessions had notably higher PDE teicoplanin concentrations compared to those with 4∼6 sessions. Therefore, PDAP patients who use intraperitoneal teicoplanin could effectively control infection by monitoring the PDE teicoplanin concentration (>15.138mg/L) on day 5 after dosing.

Peritoneal dialysis-associated peritonitis caused by Tsukamurella inchonensis: a case report and literature review

BackgroundPeritoneal dialysis (PD)-associated peritonitis is a serious complication that can lead to PD discontinuation and mortality. Tsukamurella species are uncommon opportunistic pathogens that can cause peritonitis, often necessitating catheter removal.Case presentationA 46-year-old woman with a 1.5-year history of PD presented with fever and lower abdominal pain, along with cloudy peritoneal effluent showing an elevated cell count. Empiric antibiotic therapy with ciprofloxacin, cefazolin, and ceftazidime was started for PD-associated peritonitis. The peritoneal effluent culture yielded a gram-positive rod with weak acid-fast staining. A rebound in the cell count necessitated a switch of antibiotics to meropenem and vancomycin. This led to improvement, and the treatment was switched to oral levofloxacin on day 30 and the patient was discharged on day 35. Subsequently, 16S rRNA gene sequencing confirmed the isolate as Tsukamurella inchonensis.ConclusionThis case highlights the challenges in identifying and treating Tsukamurella peritonitis. Successful treatment without catheter removal in this case suggests that early detection and appropriate antibiotics may enable catheter salvage in this rare infection. However, further research is needed to establish optimal treatment strategies.

Steady-state pharmacokinetics of lamivudine in end-stage kidney failure persons with detectable and undetectable HIV-1 RNA in peritoneal dialysis effluent

BackgroundRenally adjusted lamivudine dosages are effective. However, some of the kidney failure patients managed with lamivudine-containing regimens are failing to suppress HIV in peritoneal dialysis (CAPD) effluent. The steady-state lamivudine pharmacokinetics among these patients was evaluated.MethodsThis overnight open-label pharmacokinetic study enrolled participants living with HIV and managed with CAPD. Lamivudine levels in blood serum and CAPD effluent samples were quantified using liquid chromatography coupled with a mass spectrometer. Pharmacokinetic measures were obtained through non-compartmental analysis.ResultsTwenty-eight participants were recruited with a median antiretroviral (ARV) drug duration of 8 (IQR,4.5–10.5) years and a CAPD duration of 13.3 (IQR,3.3–31.9) months. 14.3% (4/28) had detectable unsuppressed HIV-1 viral load in CAPD effluents. The majority (78,6%,22/28) of participants received a 50 mg dose, while 10.7% (3/28), and another 10.7% (3/28) received 75 mg and 300 mg dosages, respectively. Among those treated with 75 and 300 mg, 66.7% (2/3) and 33.3% (1/3) had detectable HIV-VL in CAPD, respectively. The peritoneal membrane characteristics and CAPD system strengths were variable across the entire study population. Lamivudine exposure was increased in blood serum (50 mg-AUC0-24 h, 651.3 ng/mL; 75 mg-AUC0-24 h, 677.84 ng/mL; 300 mg-AUC0-24 h, 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC0-24 h, 384.91 ng/mL; 75 mg-AUC0-24 h, 383.24 ng/mL; 300 mg-AUC0-24 h, 2001.60 ng/mL) among the entire study population. The Cmax (50 mg, 41.5 ng/mL; 75 mg, 53.2 ng/mL; 300 mg, 199.1 ng/mL) and Cmin (50 mg, 17.8 ng/mL; 75 mg, 16.4 ng/mL; 300 mg, 76.4 ng/mL) measured in serum were within the therapeutic levels.ConclusionsSteady-state lamivudine pharmacokinetic measures were variable among the entire study population. However, the total lamivudine exposure was within the therapeutic levels.

Bacterial classification based on metagenomic analysis in peritoneal dialysis effluent of patients with chronic kidney disease.

End-stage kidney disease (ESKD) is the final stage of chronic kidney disease (CKD), in which long-term damage has been caused to the kidneys to the extent that they are no longer able to filter the blood of waste and extra fluid. Peritoneal dialysis (PD) is one of the treatments that remove waste products from the blood through the peritoneum which can improve the quality of life for patients with ESKD. However, PD-associated peritonitis is an important complication that contributes to the mortality of patients, and the detection of bacterial pathogens is associated with a high culture-negative rate. The present study aimed to apply a metagenomic approach for the bacterial identification in the PD effluent (PDE) of patients with CKD based on 16S ribosomal DNA sequencing. As a result of this investigation, five major bacteria species, namely Escherichia coli, Phyllobacterium myrsinacearum, Streptococcus gallolyticus, Staphylococcus epidermidis and Shewanella algae, were observed in PDE samples. Taken together, the findings of the present study have suggested that this metagenomic approach could provide a greater potential for bacterial taxonomic identification compared with traditional culture methods, suggesting that this is a practical and culture-independent alternative approach that will offer a novel preventative infectious strategy in patients with CDK.

The prevalence of HIV resistance mutations and their influence on the shedding of HIV-1 into peritoneal dialysis effluent.

HIV drug resistance mutations (HIVDRMs) are important determinants of therapeutic effects and outcomes even in end-stage kidney failure (ESKF) people living with HIV (PLWHIV). This study evaluated the prevalence of HIVDRMs and their effect on the shedding of HIV-1 into peritoneal dialysis (PD) effluents. This cross-sectional study of PLWHIV and having ESKF and managed with antiretroviral therapy (ART) and PD,collected enrolled patients' demographic information, clinical and laboratory data, and sequenced HIV-1 RNA in unsuppressed plasma and PD effluent samples. HIV viral load and HIVDRMs were determined using qualitative polymerase chain reaction (qPCR) and Stanford University HIVDRM Database, respectively. There were 60 participants recruited with a median age of 43.0 (interquartilerange [IQR], 38.0-47) years and were predominantly on abacavir (88.3%), lamivudine (98.3%), and efavirenz (70%) for a median duration of 8 (IQR, 5-11) years. Among participants with detectable HIV-1 in PD effluents, the prevalence of HIVDRMs was 62.5% (5/8) compared to 7.7% (4/52) among those with undetectable HIV-1 (p = 0.001) with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations predominating. On Spearman's correlation analysis, high plasma HIV levels(ρ = 0.649, p < 0.001), T-cell CD4 count (ρ = -0370, p < 0.004), serum creatinine (ρ = -0.396, p < 0.002), and white blood cell count (ρ = -0.294, p < 0.023) levels were significant factors correlated with the detection of HIV-1 in PD effluents. Moreover, HIVDRMs presence (ρ = 0.504, p < 0.001) particularly NNRTI resistance (ρ = 0.504, p < 0.001)were also significantly correlated with detection of HIV-1 in PD effluents. The presence of HIVDRMs, high plasma HIV viral load, and T-cell CD4 count were correlated with HIV-1 shedding into PD effluents.

#578 Calcium-channel blockers chyloperitoneum: an underrated complication in peritoneal dialysis

Abstract Background and Aims Bacterial peritonitis is the most feared complication for peritoneal dialysis (PD) patients. Together with abdominal pain and elevated white cell count in peritoneal effluent, the presence of a cloudy peritoneal effluent represents the main diagnostic criteria. The appearance of this last sign, even in an asymptomatic patient, always represents cause for concern and raises suspicion of an already subclinical peritonitis but can also represent other causes. Among acellular aetiologies for a cloudy peritoneal effluent, there is the presence of triglycerides, usually above 200 mg/dl, called chyloperitoneum, secondary to pancreatitis or concomitant calcium- channel blockers (CCBs) therapy. Most of dialysis patients are affected by hypertension. Considering the frequent necessity of limiting dosage of angiotensin 2 receptors blockers (ARB) and ACE inhibitors (ACE-I) for the risk of hyperkalaemia, CCBs frequently represent one of the most common prescribed antihypertensive drugs. Usually well tolerated and with limited adverse effects, literature demonstrates how they can induce, for not fully understood reasons (research supposed a role for the lipophilicity of these drugs, an impaired lymphatic absorption, an increased lympho-vascular dilatation or lymphatic hydrostatic pression) the presence of triglycerides in peritoneal effluent to levels causing chyloperitoneum. Frequently reported as anecdotical cases, especially in Asian studies, only limited information are available about influence of drug dosage or other concomitant therapies but is evident a higher frequency with lercanidipine assumption. Method We evaluated all patients undergoing peritoneal dialysis in our Centre in 2023. Chyloperitoneum (Fig. 1) diagnosis was obtained in cases of cloudy peritoneal effluent in asymptomatic patients with normal inflammatory indexes, normal white cell count on peritoneal effluent and negative cultural samples on peritoneal effluent associated with complete remission after fast peritoneal washes and reduction or discontinuation of CCBs. Results 16 patients underwent PD in our Centre during 2023: 4 automated (APD) and 12 ambulatory (CAPD). All of them were affected by hypertension and 10 of 16 (2 APD and 8 CAPD) were already in chronic therapy with CCBs (5 with lercanidipine, 4 with lacidipine and 1 with barnidipine), all at maximum accepted dosage. 4 patients presented during 2023 one or more episodes of cloudy peritoneal effluent without any sign or symptom of infection. All these patients were in CAPD and in therapy with lercanidipine and underwent to full remission after fast peritoneal washes; for 2 of them was necessary to discontinue CCBs therapy while for the other 2 dose reduction was fair. In 1 patient was recently associated oral anticoagulant therapy and in another 1 was recently associated dual antiplatelet therapy. None of these patients presented more episodes and all of them are still in PD. Among the other 8 patients in CCBs therapy without episodes of chyloperitoneum, only 1 was already in therapy with single antiplatelet therapy and none of them with double one or with oral anticoagulant. Conclusion cloudy peritoneal effluent is always cause for concern for Nephrologists since that it could represent, event without any other sign or symptom of infection, an already subclinical bacterial peritonitis. Most of dialysis patients are also affected by hypertension. Since usage of ARB and ACE-I is limited by risk of hyperkalaemia, CCBs represents one of the most prescribed antihypertensive drugs. For PD patients, however, the risk of chyloperitoneum must be considered since, even if it can be easily corrected, it could also affect therapy and patient management. Described in literature as only an anecdotical complication, our study shows that the incidence could be much higher and appears to be linked a specific molecule, lercanidipine, taken at higher dosage and to CAPD. Concomitant therapies as dual antiplatelet or oral anticoagulant therapy could represent a stimulating factor but other studies, with more numerous patients, are needed for further considerations.

#1814 Infection associated pancreatitis in peritoneal dialysis, a case report

Abstract Background and Aims Peritoneal dialysis (PD) patients seem to have a higher incidence of acute alithiasic pancreatitis. Though rare and with some suggested triggers described in the literature, this is still a poorly understood and potentially life-threatening complication. We present a 60 years old woman concluding antimicrobial therapy with an icodextrin night-dwell regimen for peritonitis presenting with epigastric pain. This work reviews our approach to cloudy effluent from non-infectious causes during an infection while managing acute pancreatitis in the PD setting. We report diagnostic difficulties and treatment considerations with a positive outcome. Method We present a 60 years old woman on PD for one year presenting to the emergency room in November of 2023 with severe epigastric pain, nausea and emesis. She suffered from stage 5 chronic kidney disease due to autosomal dominant polycystic kidney disease and had disease complications as anemia and secondary hyperthyroidism controlled within targets. She was on automated PD (APD) with glucose based solutions. She was on the 17th of 21 days antibiogram guided treatment (ceftazidime) for a Enterobacter ludwigii PD-related peritonitis with good clinical evolution and peritoneal effluent (PE) leukocyte count per μl from 1258 to 91 in 5 days. In the previous 3 months she had had 2 other infectious episodes. A bacteremic urinary tract infection to E. coli associated with peritonitis treated with antibiogram guided therapy (ceftazidime) followed by C. difficile colitis treated with oral vancomycin. During each infection period she transitioned from APD to continuous ambulatory peritoneal dialysis with an icodextrin night dwell. On admission she presented with normal vital signs, no fever, and abdominal distention with severe epigastric tenderness to palpation without muscular guarding. Her dwell exchange showed blood-tinged cloudy PE. She had hemoglobin of 11.3 g/dl, otherwise normal blood cell counts, and raised amylase (213 UI/l) and lipase (1467 UI/l). There was no elevation of transaminases, cholestatic enzymes, C-reactive protein or procalcitonin and lipidemia or hyperbilirubinemia were normal. PE cell count showed 213/μl leukocytes and 202/μl erythrocytes. Abdominal ultrasound showed no evidence of an obstructive cause. She was admitted in the surgical care unit for a conservative and watchful approach. Results On presentation we accounted for the peritonitis still under treatment, acute pancreatitis, drug therapy and recently introduced icodextrin solution. The acute alithiasic pancreatitis diagnosis was established but there was still a possible causative role of icodextrin or infection and refractory peritonitis could also not be promptly excluded. The literature suggests icodextrin and other drugs as causes for acute pancreatitis in some patients but also mentions the possibility of cloudy or hemorrhagic effluent due to abdominal inflammation processes. Considering the clinical stability, the multiple possible contributing causative agents and the differential diagnosis of refractory peritonitis we closely monitored PE cell count evolution keeping the icodextrin dwell and ceftazidime prescriptions and collected samples for bacterial and fungal culture. The cultures were negative and stability of leukocyte count and mononuclear cell predominance (Fig. 1) helped us exclude the peritonitis hypothesis and attribute the PE changes to the pancreatitis process. Conclusion Inpatient monitoring and identifying all possible causes are essential to ensure good outcomes in PD patients suffering from acute pancreatitis. Full anamnesis, physical examination and close attention to laboratory findings were key in allowing adequate antibiotic therapy and resolution of the abdominal inflammatory process at hand while maintaining an adequate PD prescription.

#1262 Risk factors of peritoneal dialysis associated peritonitis caused by gram-negative bacteria: a single-center retrospective study over 16 years

Abstract Background and Aims To analyse the clinical characteristics, pathogen distribution, and treatment outcomes of peritoneal dialysis associated peritonitis (PDAP) caused by gram-negative bacteria, and explore the risk factors for the occurrence and treatment failure of gram-negative bacterial peritonitis. Method We performed a single-center retrospective study included 544 PD patients who underwent regular follow-up between January 1, 2007, and December 31, 2022. After excluding culture-negative peritonitis, fungal peritonitis, and tuberculous peritonitis, based on the pathogens, all episodes were divided into the gram-negative peritonitis group (GNP) and the non-gram-negative peritonitis group (non-GNP). Demographic characteristics, laboratory examinations, pathogenic bacteria, and treatment outcomes were collected and compared between the two groups of peritonitis. Results Over the course of 16 years, 297 episodes of peritonitis occurred in 179 patients. Although the overall incidence of peritonitis is showing a year-on-year downward trend, the incidence of GNP has not changed significantly. However, the percentage of GNP cases among all peritonitis cases is on the rise. After excluding episodes of culture-negative peritonitis, fungal peritonitis, and tuberculous peritonitis, a total of 226 cases of peritonitis were included in the study. Among them, females accounted for 50.0%, with an average age of 63.04 ± 11.58 years and a median PD duration of 42 (21, 73) months. Escherichia coli was the main pathogen responsible for gram-negative bacterial peritonitis in our center (37/80, 46.3%), followed by Klebsiella pneumoniae (9/80, 11.3%). The GNP group had significantly higher white blood cell counts in peritoneal effluent on day 0, day 3, and day 5 after peritonitis onset compared to the non-GNP group (p &amp;lt; 0.001 for all). In terms of treatment outcomes, the GNP group had significantly higher rates of developing refractory peritonitis, treatment failure, and peritonitis-associated death compared to the non-GNP group (p &amp;lt; 0.001 for all). Multivariate logistic regression analysis revealed that enteric infection was an independent risk factor for GNP occurrence (OR = 6.315, 95% CI 3.364-11.854, p &amp;lt; 0.001). White blood cell counts on day 3 of peritoneal effluent (OR = 2.666, 95% CI 1.099-6.469, p = 0.030) and post-PDAP blood white blood cell counts (OR = 1.389, 95% CI 1.060-1.820, p = 0.017) were independent risk factors for treatment failure in GNP. Conclusion Over the past 16 years, the incidence rate of GNP in our center has shown no significant decrease, and the proportion of GNP cases has been increasing year by year. Escherichia coli is the main pathogen responsible for GNP in our center. GNP cases are more difficult to treat and have a poorer prognosis compared to non-GNP cases. Therefore, it is important to strengthen preventive measures for peritoneal dialysis patients, reduce the risk of enteric infection, and actively treat patients who have already developed gram-negative bacterial peritonitis to avoid adverse outcomes.

#996 Validation of peritoneal NGAL as a biomarker for peritonitis: a comparison between laboratory-base method and rapid stick test

Abstract Background and Aims Neutrophil gelatinase-associated lipocalin (NGAL) is a protein involved in iron homeostasis, inflammation, and fibrosis. Initially discovered in human granulocytes, NGAL is found in various tissues. In renal contexts, NGAL's small size (23-25 kDa) and positive charge aid glomerular filtration and absorption in the proximal tubule. Notably, elevated NGAL levels were identified in peritoneal fluids during peritonitis in 2009, establishing it as a biomarker for early Peritoneal Dialysis (PD)-associated peritonitis diagnosis for values more than 100 μg/L. While our medical centre currently relies on the lab-based NGAL assay (NGALlab), advancements introduce the NGAL dipstick test (NGALds), offering a rapid and semi-quantitative colorimetric assessment. This study compares NGALds with NGALlab in clinical practice, assessing NGALds's potential for early peritonitis detection in PD patients' peritoneal fluid. Method This study involves a validation of diagnostic accuracy conducted through a retrospective analysis of parallel samples obtained from peritoneal effluents. Samples were collected from both healthy patients during routine analysis and from cases with suspected or confirmed peritonitis. Both NGALlab and NGALds analyses were conducted on each sample. The analysis aimed to evaluate the performance of the new NGALds by comparing it with the established NGALlab. Peritoneal NGALlab quantification employed the standard BioPorto test (BioPorto Diagnostics, Hellerup, Denmark), utilizing a particle-enhanced turbidimetric immunoassay. The novel NGALds is a rapid semi-quantitative assay that measures NGAL levels in biological fluids through colourimetric test strips, utilizing an antibody sandwich lateral flow dipstick test. NGAL values were categorized into colour-coded levels: 25 μg/L, 50 μg/L, 100 μg/L, 150 μg/L, 300 μg/L, and 600 μg/L. Statistical analyses were performed using SPSS Statistics 26.0 software. Spearman rank correlation coefficients (Rs) assessed categorical groups of NGAL values for peritoneal NGALds and NGALlab tests. A graphic comparison of these two tests was presented through a Bland-Altman plot Results Out of 301 peritoneal effluent samples, 156 were diagnosed with suspected peritonitis by ISPD Criteria. As Table 1 showed, NGALds showed a strong correlation with NGALlab categories (Rs = 0.876, P = 10−96), successfully diagnosing 96% (150 out of 156) peritonitis cases. Discrepancies between NGALlab and NGALds, visualized in the Bland-Altman plot (Fig. 1), were most notable when NGAL values exceeded the 600 μg/L threshold. However, this difference doesn't impact clinical significance, as high NGAL values remain diagnostically for peritonitis with both methods. Conclusion In conclusion, our study underscores a significant correlation between NGAL values measured by the laboratory method (NGALlab) and the NGAL dipstick test (NGALds). Importantly, NGALds exhibited a strong capability, correctly identifying 96% of peritonitis cases determined by NGALlab. Beyond statistical correlation, the NGAL dipstick emerges as a valid alternative for swift evaluation in patients presenting symptoms suggestive of peritonitis. Its ease of use, rapidity, and semi-quantitative colorimetric assessment make NGALds a patient-friendly tool. This user-friendly characteristic holds immense potential for streamlined clinical workflows, allowing for prompt and efficient peritonitis diagnosis.

#766 A prognostic model (BLEND35) with internal validation for treatment failure in patients with peritoneal dialysis-associated peritonitis

Abstract Background and Aims Globally, peritoneal dialysis (PD)-associated peritonitis (PDAP) is a common and severe complication in PD. Early identification of high risk PDAP helps to prevent adverse outcomes. Currently, there is no recognized predictive tool for treatment failure of PDAP. Therefore, this study aimed to develop and validate a prediction model for treatment failure in patients with PDAP. Method We retrospectively collected 313 PDAP episodes occurred between January 2007 and August 2023, from real-world clinical practice in a tertiary center in Beijing, North China. The candidate predictors including patient characteristics, latest laboratory tests before PDAP, laboratory tests at PDAP onset and the causative organisms in peritoneal effluent. The prognostic model was developed from a multivariable logistic regression model with predictors selected using the stepwise backward regression. The C-statistic and the calibration curve plot were used to assess the discrimination and calibration of the prediction model. A bootstrap with 100 resampling was also performed as internal validation to further determine the robustness of the model. Results Among 313 PDAP episodes, 63 was reported treatment failure. The final model included 7 variables and was termed BLEND35 (sex, PD duration, platelet-to-lymphocyte ratio before PDAP, Gram-negative peritonitis, blood white cell counts at PDAP onset, dialysate white blood cell counts on day 3 and day 5). The C-statistic of the model was 0.936 (95% CI 0.897–0.974), revealing great discrimination. Calibration plot indicated that the model-predicted probabilities correlated well with the actual observed frequencies (Hosmer-Lemeshow test, P = 0.1223; Brier score = 0.064). Decision-curve analysis also revealed a positive net benefit. Conclusion The BLEND35 model will help to identify those with most high risk of treatment failure of PDAP and contribute to personalize and precise treatment. However, external validation is required before future application.

#758 NGAL dipstick for peritonitis: bridging the gap between rapid assessment and clinical efficiency in peritoneal dialysis

Abstract Background and Aims Neutrophil gelatinase-associated lipocalin (NGAL) is a versatile protein known for its multifunctional roles, extending beyond its conventional use as a biomarker. It actively participates in crucial biological processes such as inflammation, proliferation, and migration. This study seeks to evaluate NGALds, a recently developed dipstick test, in comparison to the established laboratory method (NGALlab) for the early detection of peritonitis related to peritoneal dialysis (PD). The focus of the investigation lies in analyzing peritoneal fluid to develop a rapid and effective diagnostic tool, aiming to enhance the management of peritonitis. Method A retrospective analysis was undertaken to validate diagnostic accuracy, utilizing parallel samples obtained from peritoneal effluents. Samples were obtained from both PD stable patients undergoing routine analysis and from PD patients with suspected or confirmed peritonitis. The assessment of NGALds involved a direct comparison with the established NGALlab. Peritoneal NGALlab quantification was conducted using the BioPorto test, employing a particle-enhanced turbidimetric immunoassay. The NGALds, a rapid semi-quantitative assay, utilized colorimetric test strips and an antibody sandwich lateral flow dipstick test. The greatest value of NGAL detected by dipstick is 600 μg/L. Statistical analyses, including Spearman rank correlation coefficients (Rs), were performed with SPSS Statistics 26.0 software. Additionally, ROC analysis was carried out using white cell count and percentage of Neutrophils in peritoneal fluids as the gold standard. Results Among the 301 peritoneal effluent samples analyzed, 156 were diagnosed with suspected peritonitis using NGALlab and ISPD criteria. Each sample underwent analyses with both NGALlab and NGALds. As depicted in Fig. 1, NGALds exhibited a robust correlation with NGALlab categories (Rs = 0.876, P &amp;lt; 0.001), accurately identifying 96% (150 out of 156) of peritonitis cases. Discrepancies between NGALlab and NGALds were most evident when NGAL values exceeded the 600 μg/L threshold. Nevertheless, these variations did not impact clinical significance, as both methods consistently diagnosed elevated NGAL values indicative of peritonitis. After ROC analysis, which yielded an AUC of 0.82 (p &amp;lt; 0.001) (Fig. 2), the Youden Index was employed to identify a threshold value of 100 μg/L for the diagnosis of suspected peritonitis. Importantly, the application of this threshold to NGALds demonstrated a positive predictive value of 0.64 and a negative predictive value of 0.87. Conclusion In conclusion, our study reinforces the significant correlation between NGAL values obtained through the laboratory standard (NGALlab) and the novel NGAL dipstick test (NGALds). Notably, NGALds exhibited high efficacy, accurately identifying 96% of peritonitis cases diagnosed by NGALlab. This robust performance positions the NGAL dipstick as a valuable and accessible alternative for rapid assessment in patients exhibiting symptoms indicative of peritonitis. The user-friendly attributes of NGALds not only make it a practical diagnostic tool but also a patient-centric one. Furthermore, the high negative predictive value provides confidence in considering NGALds as a frontline diagnostic tool for suspected peritonitis. The ease of use and prompt results open a promising avenue for improving clinical workflows, offering an opportunity for expedited and efficient peritonitis diagnosis. For instance, NGALds could find utility in centres where NGAL is unavailable in the laboratory or at the patient's home.

Exploring the Role of Cell-Free Nucleic Acids and Peritoneal Dialysis: A Narrative Review.

Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation. This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice.

Extracellular Vesicles of Patients on Peritoneal Dialysis Inhibit the TGF-β- and PDGF-B-Mediated Fibrotic Processes.

Among patients on peritoneal dialysis (PD), 50-80% will develop peritoneal fibrosis, and 0.5-4.4% will develop life-threatening encapsulating peritoneal sclerosis (EPS). Here, we investigated the role of extracellular vesicles (EVs) on the TGF-β- and PDGF-B-driven processes of peritoneal fibrosis. EVs were isolated from the peritoneal dialysis effluent (PDE) of children receiving continuous ambulatory PD. The impact of PDE-EVs on the epithelial-mesenchymal transition (EMT) and collagen production of the peritoneal mesothelial cells and fibroblasts were investigated in vitro and in vivo in the chlorhexidine digluconate (CG)-induced mice model of peritoneal fibrosis. PDE-EVs showed spherical morphology in the 100 nm size range, and their spectral features, CD63, and annexin positivity were characteristic of EVs. PDE-EVs penetrated into the peritoneal mesothelial cells and fibroblasts and reduced their PDE- or PDGF-B-induced proliferation. Furthermore, PDE-EVs inhibited the PDE- or TGF-β-induced EMT and collagen production of the investigated cell types. PDE-EVs contributed to the mesothelial layer integrity and decreased the submesothelial thickening of CG-treated mice. We demonstrated that PDE-EVs significantly inhibit the PDGF-B- or TGF-β-induced fibrotic processes in vitro and in vivo, suggesting that EVs may contribute to new therapeutic strategies to treat peritoneal fibrosis and other fibroproliferative diseases.

Expression and significance of SIRT6 in human peritoneal dialysis effluents and peritoneal mesothelial cells

Sirtuin 6 (SIRT6) can inhibit the fibrosis of many organs. However, the relationship between SIRT6 and peritoneal fibrosis (PF) in peritoneal dialysis (PD) remains unclear. We collected 110 PD patients with a duration of PD for more than 3 months and studied the influence of PD duration and history of peritonitis on SIRT6 levels in PD effluents (PDEs). We also analyzed the relationship between SIRT6 levels in PDEs and transforming growth factor beta 1 (TGF-β1), IL-6, PD duration, peritoneal function, PD ultrafiltration (UF), and glucose exposure. We extracted human peritoneal mesothelial cells (HPMCs) from PDEs and measured the protein and gene expression levels of SIRT6, E-cadherin, vimentin, and TGF-β1 in these cells. Based on the clinical results, we used human peritoneal mesothelial cells lines (HMrSV5) to observe the changes in SIRT6 levels and mesothelial-to-mesenchymal transition (MMT) after intervention with PD fluid. By overexpressing and knocking down SIRT6 expression, we investigated the effect of SIRT6 expression on E-cadherin, vimentin, and TGF-β1 expression to elucidate the role of SIRT6 in mesothelial-to-epithelial transition in PMCs. Results: (1) With the extension of PD duration, the influence of infection on SIRT6 levels in PDEs increased. Patients with the PD duration of more than 5 years and a history of peritonitis had the lowest SIRT6 levels. (2) SIRT6 levels in PDEs were negatively correlated with PD duration, total glucose exposure, TGF-β1, IL-6 levels, and the dialysate-to-plasma ratio of creatinine (Cr4hD/P), but positively correlated with UF. This indicates that SIRT6 has a protective effect on the peritoneum. (3) The short-term group (PD ≤ 1 year) had higher SIRT6 and E-cadherin gene and protein levels than the mid-term group (1 year < PD ≤ 5 years) and long-term group (PD > 5 years) in PMCs, while vimentin and TGF-β1 levels were lower in the mid-term group and long-term group. Patients with a history of peritonitis had lower SIRT6 and E-cadherin levels than those without such a history. (4) After 4.25% PD fluid intervention for HPMCs, longer intervention time resulted in lower SIRT6 levels. (5) Overexpressing SIRT6 can lead to increased E-cadherin expression and decreased vimentin and TGF-β1 expression in HPMCs. Knocking down SIRT6 expression resulted in decreased E-cadherin expression and increased vimentin and TGF-β1 expression in HPMCs. This indicates that SIRT6 expression can inhibit MMT in HPMCs, alleviate PF associated with PD, and have a protective effect on the peritoneum.

SPHK1/S1P/S1PR pathway promotes the progression of peritoneal fibrosis by mesothelial-mesenchymal transition.

Long-term exposure to non-physiologically compatible dialysate inevitably leads to peritoneal fibrosis (PF) in patients undergoing peritoneal dialysis (PD), and there is no effective prevention or treatment for PF. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid produced after catalysis by sphingosine kinase (SPHK) 1/2 and activates signals through the S1P receptor (S1PR) via autocrine or paracrine. However, the role of SPHK1/S1P/S1PR signaling has never been elucidated in PF. In our research, we investigated S1P levels in peritoneal effluents and demonstrated the role of SPHK1/S1P/S1PR pathway in peritoneal fibrosis. It was found that S1P levels in peritoneal effluents were positively correlated with D/P Cr (r = 0.724, p < .001) and negatively correlated with 4 h ultrafiltration volume (r = -0.457, p < .001). S1PR1 and S1PR3 on peritoneal cells were increased after high glucose exposure invivo and invitro. Fingolimod was applied to suppress S1P/S1PR pathway. Fingolimod restored mouse peritoneal function by reducing interstitial hyperplasia, maintaining ultrafiltration volume, reducing peritoneal transport solute rate, and mitigating the protein expression changes of fibronectin, vimentin, α-SMA, and E-cadherin induced by PD and S1P. Fingolimod preserved the morphology of the human peritoneal mesothelial cells, MeT-5A, and moderated the mesothelial-mesenchymal transition (MMT) process. We further delineated that SPHK1 was elevated in peritoneal cells after high glucose exposure and suppression of SPHK1 in MeT-5A cells reduced S1P release. Overexpression of SPHK1 in MeT-5A cells increased S1P levels in the supernatant and fostered the MMT process. PF-543 treatment, targeting SPHK1, alleviated deterioration of mouse peritoneal function. In conclusion, S1P levels in peritoneal effluent were correlated with the deterioration of peritoneal function. SPHK1/S1P/S1PR pathway played an important role in PF.

Hemoperitoneum Related with Peritoneal Dialysis in A Female Adolescent: it is Not as Frightening as it Seems

Although hemoperitoneum is a benign and common complication of chronic peritoneal dialysis the apperance of the effluent will be devastating for the patients. In women of reproductive age group gynecological causes are the common etiological factors. A 17 years old girl who had been on automated peritoneal dialysis for six months was admitted because of bloody effluent lasting for two days. At admission she described mild abdominal pain; physical examination was unremarkable and bleeding time and coagulation profile was normal. Abdominal ultrasound revealed hemorrhagic cysts on left ovary. Peritoneal effluent was cleared by using rapid exchanges with room temperature dialysate. Hemoperitoneum is a well recognized complication of peritoneal dialysis in women of reproductive age.Abdominal ultrasound is the first, easily applicable and reliable diagnostic modality in order to detect underlying causes of hemoperitoneum. Performing rapid exchanges with cold-room temperature dialysate is the mainstay of treatment.

Validation of peritoneal neutrophil gelatinase-associated lipocalin as a biomarker for peritonitis: A comparison between laboratory-base method and rapid stick test

ABSTRACT Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a multifunctional protein with roles beyond biomarker status, influencing critical processes. This study aimed to assess dipstick test for NGAL (NGALds), a novel dipstick test, against the established laboratory-based NGAL (NGALlab) method for early peritonitis detection, focusing on peritoneal fluid analysis to provide a rapid and cost-effective diagnostic tool for peritonitis management. Methods: Conducted at San Bortolo Hospital, Italy, this retrospective study collected samples from suspected or confirmed peritonitis cases between May 1, 2021, and December 31, 2021. Samples included peritoneal dialysate effluents (PDE) and underwent white blood cell counts, NGALds, NGALlab, and effluent culture. Results: The study analyzed 27 peritonitis cases, involving 133 PDE samples from 22 patients. NGALds exhibited a strong correlation (Rs = 0.732, P &lt; 0.05) with NGALlab, particularly for medium to high-risk peritonitis cases, with a 98% accuracy rate. Conclusion: NGALds effectively aligns with NGALlab for peritonitis diagnosis, offering a valuable diagnostic tool, particularly suitable for point-of-care and resource-limited healthcare settings. Further research should investigate its correlation with neutrophil levels in PDE, solidifying NGALds as an accessible and efficient resource for peritonitis management.