Dialysis Effluent Research Articles

Predictors of encapsulated peritoneal sclerosis in patients undergoing peritoneal dialysis using neutral-pH dialysate.

Encapsulated peritoneal sclerosis (EPS) is a serious complication in patients undergoing peritoneal dialysis (PD). Neutral-pH dialysate is associated with less peritoneal damage and a lower incidence of EPS than conventional PD solution. However, monitoring for peritoneal damage and predicting EPS remain important during PD therapy. We measured the mesothelial cell area, dialysate-to-plasma ratio of creatinine after 4h, and concentrations of the potential biological markers effluent fibrin degradation products (eFDPs), cancer antigen-125, and interleukin-6 in the effluent dialysate from patients who had been undergoing PD therapy for > 5years in our hospital. These biomarkers were obtained from the drainage fluid of the final measurement of peritoneal equilibration testing before withdrawal from PD therapy. The concentrations of these potential biomarkers were measured in 39 patients who withdrew from PD therapy and were enrolled in the study. Three participants developed EPS after withdrawing PD. The dialysate-to-plasma ratio of creatinine, area of mesothelial cells, and interleukin-6 appearance rate in participants who developed EPS tended to be higher than those in patients who did not, but there were no significant differences. Significantly more eFDPs were in participants who developed EPS than in those who did not (138.5 ± 15.1 vs. 32.9 ± 7.4µg/mL, P = 0.002). There was no difference in the cancer antigen-125 appearance rate between the groups. A cut-off value of eFDPs ≥ 119.1µg/mL was optimal for predicting EPS (P = 0.006, specificity = 0.972, sensitivity = 1.000). This study shows that eFDPs may be a useful biological marker for predicting EPS in patients undergoing PD using neutral-pH dialysate.

Autotaxin concentrations in peritoneal dialysis effluent reflect peritoneal function.

Peritoneal equilibration test (PET) has been used to monitor peritoneal function. A more convenient marker would be useful in clinical situations including home medical care. Autotaxin is known to leak into the interstitium as vascular permeability increases during the progression of tissue fibrosis. Therefore, we hypothesized that autotaxin concentrations in peritoneal dialysis (PD) effluent might reflect peritoneal function. This study enrolled 45 patients undergoing PD from 2016 to 2021. Autotaxin concentrations measured in PD effluent were evaluated for their associations with markers obtained from PET. Mean age was 69 years, and 33 patients were men. Univariate and multivariate analyses revealed that autotaxin concentrations are associated with dialysate/plasma creatinine ratio, end/start dialysate glucose ratio, and the dip in the dialysate sodium concentration, a marker of ultrafiltration capacity, at baseline (all p < 0.05). Autotaxin concentrations in PD effluent might be an adjunct marker that reflects peritoneal function.

Improved Culture Positivity Rate after Modified Culture Technique of Dialysis Effluent Fluid in Peritoneal Dialysis-related Peritonitis Cases

Improved Culture Positivity Rate after Modified Culture Technique of Dialysis Effluent Fluid in Peritoneal Dialysis-related Peritonitis Cases

Pantoea peritonitis in peritoneal dialysis: a report of two cases and literature review

BackgroundPantoea spp., a non-encapsulated, non-spore-forming Gram-negative rod bacterium that belongs to the Erwiniaceae family, can be found as a colonizer in humans, plants, and the environment, such as water and soil. Although it has the pathogenic potential to cause disease in humans, patients infected with this pathogen generally experience favorable outcomes. In this article, we present two cases of peritoneal dialysis (PD)-associated peritonitis caused by Pantoea spp. along with literature review.Case presentationThe first case is a 66-year-old male patient with end-stage kidney disease (ESKD) on PD, admitted for P. dispersa peritonitis. He presented with abdominal pain and cloudy dialysis effluent, responding well to intraperitoneal vancomycin and cefepime. Antibiotics were deescalated to ceftazidime monotherapy on the basis of antibiotic susceptibility testing. Despite initial recovery with a 3-week course of antibiotics, he developed recurrent peritonitis with P. dispersa, necessitating PD catheter removal and transition to hemodialysis. The second case is a 42-year-old male patient with ESKD on PD who was admitted after 6 days of bloody PD fluid without trauma or associated symptoms. With elevated PD fluid cell counts and positive PD fluid culture showing Streptococcus mitis and P. agglomerans, he was empirically treated for PD-associated peritonitis with intraperitoneal vancomycin and cefepime. Due to a suboptimal response in repeat PD fluid cell counts at day 5, the PD catheter was removed, and he was switched to hemodialysis, followed by a 3-week course of intravenous ceftriaxone.ConclusionsWe described two unique cases of Pantoea peritonitis in PD, recurrent P. dispersa peritonitis and refractory P. agglomerans peritonitis, both of which resulted in PD catheter removal. Our cases indicate the formation of bacterial biofilm as a potential reason for recurrence of infection and underscores the importance of vigilant monitoring and need for PD catheter removal in Pantoea peritonitis.

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.

Rare skin color changes in an acute pancreatitis patient undergoing maintenance hemodialysis

BackgroundSkin conditions are common in patients on maintenance hemodialysis and those with pancreatitis. However, there is a lack of research on dermatological issues in patients who have both hemodialysis and pancreatitis concurrently.Case presentationA 62-year-old male patient with a 4-year history of maintenance hemodialysis (MHD) presented with pain and was diagnosed with acute pancreatitis and gallbladder stones. Markedly elevated blood amylase, creatine kinase, and myoglobin were noted, alongside a purplish-red skin discoloration. Treatment included inhibition of digestive fluid secretion, anti-infection measures, blood purification, fasting, rehydration, and symptomatic care. Notably, continuous renal replacement therapy (CRRT) combined with hemoperfusion (HP) was employed. The patient’s dialysis effluent initially appeared red. Upon examination of the patient’s peripheral blood smear, red blood cell debris was not observed. The dialysis effluent (on Day 0) was analyzed, revealing no hemoglobin (0 g/L) but an elevated myoglobin concentration of 80.4 U/L. After the therapeutic intervention, the indicators, including the blood amylase, C-reactive protein, total bilirubin, creatine kinase, and myoglobin were improved. The patient experienced resolution of sternal and upper abdominal pain within two days. After four consecutive days of CRRT and HP treatment, the skin color returned to normal, alongside improved clarity of the dialysis effluent. Subsequently, the patient’s method of blood purification was reverted to conventional hemodialysis. On the eighth day of hospitalization, the patient resumed normal diet and was discharged.ConclusionsIn the case of the current patient with acute pancreatitis undergoing MHD, it is noteworthy to report the observation of a unique purplish-red skin discoloration. This phenomenon may be attributable to inflammation resulting from acute pancreatitis, and the retention of myoglobin within the body.

Peritoneal-dialysis-associated peritonitis due to Staphylococcus sciuri: a case report and literature review

BackgroundPeritoneal-dialysis-associated peritonitis is a serious complication of peritoneal dialysis; prevention and treatment are crucial to reduce patient morbidity and mortality. Staphylococcus sciuri is an organism that, although present in several animal species, rarely causes disease in humans, particularly in patients undergoing peritoneal dialysis.Case presentationA 54-year-old man with end-stage kidney disease on continuous ambulatory peritoneal dialysis was admitted to the emergency department with nausea, vomiting, slight abdominal distention, and cloudy peritoneal dialysis effluent. Relevant medical history included occupational exposure to different animal species. The white blood cell count in the peritoneal dialysis fluid sample was 11,200 cells/mm3 with 90% polymorphonuclear cells. Peritoneal-dialysis-associated peritonitis was diagnosed. Empirical antibiotic treatment was started according to the International Society for Peritoneal Dialysis guidelines. Staphylococcus sciuri was identified in the peritoneal dialysis effluent culture by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The treatment was modified on the basis of the sensitivity results. Medical cure was established on the basis of the negative result of the dialysate culture and absence of alterations in the cell count with differential after the end of treatment. The patient was instructed to be careful when administering peritoneal dialysis, especially in the care involved in being in contact with animals.ConclusionsThis article highlights the importance of Staphylococcus sciuri as a significant pathogen due to its virulence and antibiotic resistance, especially in patients undergoing peritoneal dialysis. Prevention strategies as well as timely diagnosis and treatment compliance according to the International Society for Peritoneal Dialysis are essential for successful outcomes.

Comparison of hemodialysis urea clearance using spent dialysate and Kt/Vurea equations.

Dialysis adequacy is traditionally calculated from pre- and post-hemodialysis session serum urea concentrations and expressed as the urea reduction ratio, or Kt/Vurea. However, with increasing hemodiafiltration usage, we wished to determine whether there were any differences between standard Kt/Vurea equations and directly measured spent dialysate urea clearance. Urea clearance was measured from collected effluent dialysate and compared with various other methods of Kt/Vurea calculation, including change in total body urea from measuring pre- and post-total body water with bioimpedance and the Watson equation, by standard Kt/V equations, and online clearance measurements using effective ionic dialysance (OLC). We compared urea clearance in 41 patients, 56.1% male, mean age 69.3 ± 12.6 years with 87.8% treated by hemodiafiltration. Reduction in total body urea was greater when estimating changes in total body urea, compared to measured dialysate losses of 58.4% (48.5-67.6) vs 71.6% (62.1-78), p < 0.01. Sessional urea clearance (Kt/Vurea) was greater using the online Solute-Solver program compared to OLC, median 1.45(1.13-1.75) vs 1.2 (0.93-1.4), and 2nd generation Kt/V equations1.3 (1.02-1.66), p < 0.01, but not different from estimated total body urea clearance 1.36 (1.15-1.73) and dialysate clearance 1.36 (1.07-1.76). The mean bias compared to the Solute-Solver program was greatest with OLC (-0.25), compared to second-generation equations (-0.02), estimated total body clearance (-0.02) and measured dialysate clearance (-0.01). This study demonstrated that the result from equations estimating urea clearance indirectly from pre- and postblood samples from hemo- and hemodiafiltration treatments was highly correlated with direct measurements of dialysate urea clearance.

Cystatin C and Kidney Function Recovery in Patients Requiring Continuous Kidney Replacement Therapy for Acute Kidney Injury.

Plasma cystatin C is a reliable marker to estimate kidney function; however, it is unknown whether this remains true in patients receiving continuous kidney replacement therapy (CKRT). Herein, we tested the hypothesis that lower concentrations of plasma cystatin C during the first three days of CKRT would predict kidney function recovery. We performed a retrospective observational study of 72 patients from a 126-patient, single-center CKRT study. We studied two a priori defined cohorts of patients without advanced CKD who had acute kidney injury requiring CKRT (AKI-CKRT): 1) with early kidney function recovery defined as liberation from KRT within seven days of CKRT initiation versus 2) with delayed kidney function recovery defined as receipt of KRT for >21 days or death while on KRT. Subsequent analysis included patients with advanced CKD and intermediate kidney function recovery (liberation between 8 and 21 days). Cystatin C was then measured on stored plasma, urine, and dialysis effluent collected prior to CKRT initiation and on days 1, 2, and 3 of CKRT. Plasma cystatin C was significantly lower in patients with early kidney function recovery in comparison to patients with delayed kidney function recovery on days 1 (1.79 vs. 2.39mg/L), 2 (1.91 vs. 2.38mg/L) and 3 (2.04 vs. 2.67mg/L) of CKRT. Sieving coefficient and CKRT clearance of cystatin C were similar for patients with early and delayed kidney function recovery. The lowest plasma cystatin C concentration on days 1-3 of CKRT predicted early kidney function recovery with an area under the receiver operating curve of 0.77 (P = 0.002), positive likelihood ratio of 5.60 for plasma cystatin C <1.30mg/L, and negative likelihood ratio of 0.17 for plasma cystatin C ≥1.88mg/L. Lower plasma cystatin C concentrations during the first three days of CKRT are associated with early kidney function recovery.

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.

Severe respiratory acidosis contributing to refractory hyperkalemia: a case series of COVID-19 patients with renal failure

Introduction: Respiratory acidosis (RA) is not known to cause severe hyperkalemia. However, an exception to this general rule was observed in three patients with severe COVID-19 complicated with renal failure in our center. Objectives: The current study investigated the explanation for hyperkalemia refractory to renal replacement therapy in patients with severe COVID-19 with hypercarbia and renal failure in a tertiary care center. Patients and Methods: In this study, we present a case series of three patients with severe COVID-19 with hypercarbia and dialysis-requiring renal failure who developed persistent hyperkalemia refractory to renal replacement therapy. We studied various causes of persistent hyperkalemia, such as acid‒base disorder, a high turnover state, exogenous administration, rhabdomyolysis, and hypoaldosteronism. Results: All three patients initially presented with episodes of severe hyperkalemia, which were ameliorated after RA was corrected. All of these patients had worsening pulmonary function, after which the hyperkalemia could not be corrected, corresponding to persistent RA. The evidence that there was a contribution of RA to hyperkalemia was further strengthened by the observations of patient 1, in whom the hyperkalemia was only corrected after changing ventilator settings and who was unresponsive to dialysis. We studied the dialysate effluent in patient 3, and the results showed satisfactory removal of potassium with no improvement in the high serum potassium levels. Another interesting finding was that although the dialysate sodium concentration was greater than the serum sodium concentration, there was a decrease in the serum sodium concentration, indicating a reduced movement of sodium into the extracellular space. Conclusion: In our study, metabolic acidosis alone could not explain the high serum potassium levels. Moreover, hyperkalemia was corrected after RA was corrected, indicating that the latter might have been the predominant cause of hyperkalemia in these scenarios. The presence of renal failure and low serum bicarbonate levels might have been the factors contributing to decreased Na+-K+-ATPase activity in the setting of RA, which contributed to severe hyperkalemia in all three patients.

Calcium mass balance in adults during single hemodialysis and hemodiafiltration treatments using lower calcium dialysate concentrations.

Debate continues as to the optimum hemodialysis (HD) dialysate calcium concentration. Although current guidelines advocate 1.25-1.5 mmol/L, some investigators have suggested these may cause calcium gains. As such we investigated whether using dialysate calcium of 1.25 mmol/L risked calcium gains, and whether there were differences between hemodiafiltration and high flux HD. We continuously collect an aliquot of effluent dialysate during dialysis sessions, and calculated dialysis calcium mass balance by the difference between the amount of calcium delivered as fresh dialysate and that lost in effluent dialysate. We studied 106 stable outpatients, 64% male, mean age 64.4 ± 16.2 years, median dialysis vintage 32 (22-60) months. Most sessions (69%) used a 1.0 mmol/L calcium dialysate, with a median sessional loss of 13.7 (11.5-17.1) mmol, whereas using 1.25 mmol/L the median loss was 7.4 (4.9-10.1) mmol, but with 6.9% had a positive balance (p = 0.031 vs dialysate calcium 1.0 mmol/L). Most patients (85.8%) were treated by hemodiafiltration, but there was no difference in sessional losses (11.7 (8.4-15.8) vs 13.5 (8.1-16.8)) with high flux HD. Dialysis sessional calcium balance was associated with the use of lower dialysate calcium concentration (β -19.5, 95% confidence limits (95%CL) -27.7 to -11.3, p < 0.001), and sessional duration (β 0.07 (95% CL) 0.03-012, p = 0.002). Ideally, the choice of dialysate calcium should be individualized, but clinicians should be aware, that even when using a dialysate calcium of 1.25 mmol/L, some patients are at risk of a calcium gain during hemodiafiltration and high-flux hemodialysis.

Peritoneal dialysis-associated peritonitis, caused by superior mesenteric artery thrombosis with intestinal necrosis: a case report.

Peritoneal dialysis (PD)-associated peritonitis is a common complication of PD. Enteric peritonitis is defined as peritonitis arising from an intestinal or intra-abdominal organ source. The delay in the diagnosis or treatment of enteric peritonitis has been reported to increase mortality. Therefore, the early consideration of enteric peritonitis, particularly in cases of culture-negative peritonitis, is imperative. A 67-year-old Japanese man who had been undergoing PD for 3years, was admitted to our hospital with a diagnosis of PD-associated peritonitis. A month previously, he experienced a bleeding gastric ulcer, which led to severe anemia (hemoglobin 6.3mg/dL), followed by thrombocytosis. On admission, peritoneal fluid analysis showed a high white blood cell count (WBC: 8,570 /µL), with neutrophils predominating (74.5%). Cultures of both his dialysis effluent and blood were negative. After admission, the WBC count of the dialysis effluent gradually decreased alongside antibiotic therapy, but the patient's abdominal pain did not improve. After 4days, enhanced computed tomography showed superior mesenteric artery (SMA) thrombosis and intestinal necrosis. Therefore, emergency intestinal resection and PD catheter removal were performed, and then antithrombosis therapy was initiated. Because the patient's abdominal pain was improved and platelet count and D-dimer concentration were reduced by these treatments, he was discharged from the hospital after 47days. Thus, we report a rare case of culture-negative PD-associated peritonitis, which was caused by SMA thrombosis and intestinal necrosis. It is likely that combination of severe calcification of SMA and prolonged thrombocytosis secondary to the severe anemia contributed to the thrombosis.

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.

#3017 Renal-friendly lamivudine dosages are unlikely to contribute to HIV-1 shedding into PD effluents—an open label non-randomized pharmacokinetics study

Abstract Background and Aims Renally 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. Method This 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 spectrometry. Pharmacokinetic measures were obtained through non-compartmental analysis. Results Twenty-eight participants were recruited with a median ARV duration of 8 (IQR, 4.5-10.5) years and a CAPD duration of 13.3 (IQR, 3.3-31.9) months. The majority, 78.6% (22/20) of participants received a 50 mg dose and 25% (1/4) had a detectable HIV viral load (HIV-VL) in CAPD, 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, 50% (2/4) and 25% (1/4) 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 hours, 651.3 ng/mL; 75 mg-AUC0-24 hours, 677.84 ng/mL; 300 mg-AUC0-24 hours, 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC0-24 hours, 384.91 ng/mL; 75 mg-AUC0-24 hours, 383.24 ng/mL; 300 mg-AUC0-24 hours, 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. Conclusion Steady-state lamivudine pharmacokinetic measures were variable among the entire study population; however, the total lamivudine exposure was within the therapeutic levels.

#3064 Adequacy of urea and middle molecules clearance with online hemodiafiltration (HDF) for dialysate flow rates of 300 vs 500 ml/min

Abstract Background and Aims Trial cross design to determine non-inferiority in the adequacy of urea and middle molecules (B2 microglobulin, myoglobin and prolactin) clearance with 300 ml/min vs 500 ml/min of dialysate flow rate Method We have evaluated 2542 online HDF sessions (over 3 × 3 months trial cross design) in 50 patients in online HDF with sessions three times a week lasting 4 hours each. The online data from the DDM module of the Nikkiso DBB-EXA monitor were crossed, measuring urea in the dialysate effluent every 20 seconds by absorptiometry with UV light with age, sex, dialyzer, DM, BMI. In the laboratory, urea and B2 microglobulin, prolactin and mioglobin were measured at 300 and 500 ml/min, calculating the reduction rates of these toxins. We analyzed the data of 50 patients, in 25 patients, the first 3 months involved a dialysate flow rate 300 ml/min, followed by subsequent three months at 500 ml/min and vice versa for the remaining patients. They used the same dialyzer during the 3 × 3 months of the study as well as card programming. To study whether the change in dialysate flow influenced the effectiveness of dialysis, “generalized models with repeated measurements over time correcting the temporal autocorrelation with the covariance matrix AR1” were used the following parameters: kt/v, eKt/V and URR Results 23 men, 27 women, average age 70 years Kt/V.- The variables that are related to the Kt/v values throughout the sessions are: The effect of dialysate Flow 500 ml is statistically non-significant and positive (beta = 0.01, 95% CI (−0.06, 0.08),p0.707 The effective gender (female) is statistically significant and positive (beta = 0.26, 95% CI (0.15, 0.38) p &amp;lt; 0.001 The effect of DM is statistically non-significant and negative (beta = −0.1, 95% CI (−0.22, 0.01) p = 0.081 The effect of period 2 is statistically non-significant and negative (beta = −0.02, 95% CI (−0.08, 0.03) p = 0.37 eKt/V.- The effect of dialysate Flow 500 ml is statistically non-significant and positive (beta = 0.05, 95% CI (−0.02, 0.12),p0.138 The effect gender (female) is statistically significant and positive (beta = 0.22, 95% CI (0.11, 0.33) p &amp;lt; 0.001 The effect of DM is statistically non-significant and negative (beta = −0.10, 95% CI (−0.20, 0.01) p = 0.082 The effect of period 2 is statistically non-significant and negative (beta = −2.44e.03, 95% CI (−0.06, 0.05) p = 0.930 URR.- The effect of dialysate Flow 500 ml is statistically non-significant and positive (beta=1.19, 95% CI (−0.22, 2.60),p0.098 The effect of gender (female) is statistically significant and positive (beta=5.52, 95% CI (3.48, 7.56) p &amp;lt; 0.001 Didn´t found significant difference between mean of RRb2 microglobulin, RRProlactin and RRMioglobin with dialysate flow 300 vs 500 ml/min Conclusion Urea and B2 microglobulin, myoglobin and prolactin depuration is adequate at both dialysate flow rate 500 ml/min and 300 ml/min in the evaluated patients.

Does online high-volume hemodiafiltration offer greater efficiency and sustainability compared with high-flux hemodialysis? A detailed simulation analysis anchored in real-world data.

Recent findings, including the CONVINCE (comparison of high-dose HDF with high-flux HD) study report, suggest the superiority of high-volume hemodiafiltration (HDF) over high-flux hemodialysis (HD) in improving patients' outcomes. Despite positive patient outcomes, concerns have arisen about the potential negative environmental impact of high-volume HDF, as it may lead to increased water and dialysis fluid consumption and higher waste production. In this manuscript, we address the environmental impact of high-volume HDF, focusing on three key factors: water treatment consumption, dialysis fluid consumption, and solute efficiency markers of HD and HDF. By optimizing HDF prescription through adjustments in operational capabilities, while keeping a high blood flow (i.e.,>350ml/min) such as reducing the QD/QB ratio to 1.2 rather than 1.4 or 1.5 and incorporating automated ultrafiltration and substitution control, we demonstrate that HDF delivers a higher dialysis dose for small- and middle-molecule uremic compounds with the same dialysis fluid consumption, and at equal dialysis doses dialysis fluid consumption is reduced. This finding is supported by real-world data from 26031 patients who underwent high-volume postdilution HDF at a reduced dialysis flow (430mL/min) and achieved an effective OCMKt/V of 1.70 (where "OCM" stands for online clearance measurement, "K" represents effective dialysis clearance and "V" denotes total body water measured by multifrequency bioimpedance). In addition, simulation modeling calculations, using blood extraction coefficient, dialysate saturation coefficient and solute clearances with urea (small molecular weight) and β2-microglobulin (middle molecular weight), consistently show the superiority of postdilution HDF to HD. This holds true even with a significant reduction in dialysis flow down to 430mL/min, reflecting QD/QB ratio of 1.2. Postdilution HDF generates high ultrafiltrate flow (up to 35% of blood flow), delivering saturated ultrafiltrate to the lower solute concentration containing effluent dialysate, thus enhancing solute clearance which opens the way to reduce the dialysis flow. In conclusion, our analysis, combining simulation and real-world data, suggests that postdilution HDF could be a more environmentally friendly treatment option compared with conventional HD. Additionally, automated user-friendly functions that minimize dialysis fluid use can further strengthen this environmental benefit while enhancing efficiency.

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.