Improving Solute Clearances by Hemodialysis

Lee, Seolhyun; Sirich, Tammy L.; Meyer, Timothy W.

doi:10.1159/000524512

Cited by 4 publications

(3 citation statements)

References 98 publications

(135 reference statements)

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“…CLHD is the clearance rate of dialysis, BFR is the blood flow rate, DFR is the dialysate flow rate, and KoA is the product of the mass transfer coefficient and membrane surface area of Dialyzers used in clinical studies. The KoA was estimated to be 188 mL/min ( Lee et al, 2022 ). BFR, DFR, and the duration of dialysis were adjusted according to the parameter settings of the clinical study.…”

Section: Methodsmentioning

confidence: 99%

Physiologically based pharmacokinetic-pharmacodynamic evaluation of meropenem in CKD and hemodialysis individuals

et al. 2023

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Objective: Chronic kidney disease (CKD) has significant effects on renal clearance of drugs. The application of antibiotics in CKD patients to achieve the desired therapeutic effect is challenging. This study aims to determine meropenem plasma exposure in the CKD population and further investigate optimal dosing regimens.Methods: A healthy adult PBPK model was established using the meropenem’s physicochemical parameters, pharmacokinetic parameters, and available clinical data, and it was scaled to the populations with CKD and dialysis. The differences between the predicted concentration, Cmax, and AUClast predicted and observed model values were assessed by mean relative deviations (MRD) and geometric mean fold errors (GMFE) values and plotting the goodness of fit plot to evaluate the model’s performance. Finally, dose recommendations for CKD and hemodialysis populations were performed by Monte Carlo simulations.Results: The PBPK models of meropenem in healthy, CKD, and hemodialysis populations were successfully established. The MRD values of the predicted concentration and the GMFE values of Cmax and AUClast were within 0.5–2.0-fold of the observed data. The simulation results of the PBPK model showed the increase in meropenem exposure with declining kidney function in CKD populations. The dosing regimen of meropenem needs to be further adjusted according to the renal function of CKD patients. In patients receiving hemodialysis, since meropenem declined more rapidly during the on-dialysis session than the off-dialysis session, pharmacodynamic evaluations were performed for two periods separately, and respective optimal dosing regimens were determined.Conclusion: The established PBPK model successfully predicted meropenem pharmacokinetics in patients with CKD and hemodialysis and could further be used to optimize dosing recommendations, providing a reference for personalized clinical medication.

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Section: Methodsmentioning

confidence: 99%

Physiologically based pharmacokinetic-pharmacodynamic evaluation of meropenem in CKD and hemodialysis individuals

et al. 2023

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“…The dissociation does not occur until the concentration of the unbound fraction decreases, a process that unfolds gradually due to its dialysis over the course of the session. Despite the rapid dissociation capacity of albumin [ 79 ], the equilibrium is eventually restored as the bound fraction is gradually released. However, the passage of toxins from the tissue compartment to the blood is very slow and constitutes the most limiting factor.…”

Section: Pbut Clearance Strategiesmentioning

confidence: 99%

Displacing the Burden: A Review of Protein-Bound Uremic Toxin Clearance Strategies in Chronic Kidney Disease

Sánchez-Ospina,

Mas-Fontao,

Gracia-Iguacel

et al. 2024

JCM

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Uremic toxins (UTs), particularly protein-bound uremic toxins (PBUTs), accumulate in chronic kidney disease (CKD) patients, causing significant health complications like uremic syndrome, cardiovascular disease, and immune dysfunction. The binding of PBUTs to plasma proteins such as albumin presents a formidable challenge for clearance, as conventional dialysis is often insufficient. With advancements in the classification and understanding of UTs, spearheaded by the European Uremic Toxins (EUTox) working group, over 120 molecules have been identified, prompting the development of alternative therapeutic strategies. Innovations such as online hemodiafiltration aim to enhance the removal process, while novel adsorptive therapies offer a means to address the high affinity of PBUTs to plasma proteins. Furthermore, the exploration of molecular displacers, designed to increase the free fraction of PBUTs, represents a cutting-edge approach to facilitate their dialytic clearance. Despite these advancements, the clinical application of displacers requires more research to confirm their efficacy and safety. The pursuit of such innovative treatments is crucial for improving the management of uremic toxicity and the overall prognosis of CKD patients, emphasizing the need for ongoing research and clinical trials.

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“…Adsorption is a method for removal of molecules via attachment to various sorbents because of chemical affinity to ion-exchange resins and chemisorbents [153]. Sorbents and adsorptive technologies provide a means to remove highly protein-bound solutes which are not effectively cleared by diffusion or convection [154].…”

Section: Emerging Topic #2: the Use Of Ebp To Treat Sepsis Covid-19 A...mentioning

confidence: 99%

Proceedings of the 2022 UAB CRRT Academy: Non-Invasive Hemodynamic Monitoring to Guide Fluid Removal with CRRT and Proliferation of Extracorporeal Blood Purification Devices

Teixeira,

Zeidman,

Beaubien-Souligny

et al. 2023

Blood Purif

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In 2022, we celebrated the 15th anniversary of the University of Alabama at Birmingham (UAB) Continuous Renal Replacement Therapy (CRRT) Academy, a 2-day conference attended yearly by an international audience of over 100 nephrology, critical care, and multidisciplinary trainees and practitioners. This year, we introduce the proceedings of the UAB CRRT Academy, a yearly review of select emerging topics in the field of critical care nephrology that feature prominently in the conference. First, we review the rapidly evolving field of non-invasive hemodynamic monitoring and its potential to guide fluid removal by renal replacement therapy (RRT). We begin by summarizing the accumulating data associating fluid overload with harm in critical illness and the potential for harm from end-organ hypoperfusion caused by excessive fluid removal with RRT, underscoring the importance of accurate, dynamic assessment of volume status. We describe four applications of point-of-care ultrasound used to identify patients in need of urgent fluid removal or likely to tolerate fluid removal: lung ultrasound, inferior vena cava ultrasound, venous excess ultrasonography, and Doppler of the left ventricular outflow track to estimate stroke volume. We briefly introduce other minimally invasive hemodynamic monitoring technologies before concluding that additional prospective data are urgently needed to adapt these technologies to the specific task of fluid removal by RRT and to learn how best to integrate them into practical fluid-management strategies. Second, we focus on the growth of novel extracorporeal blood purification devices, starting with brief reviews of the inflammatory underpinnings of multiorgan dysfunction and the specific applications of pathogen, endotoxin, and/or cytokine removal and immunomodulation. Finally, we review a series of specific adsorptive technologies, several of which have seen substantial clinical use during the COVID-19 pandemic, describing their mechanisms of target removal, the limited existing data supporting their efficacy, ongoing and future studies, and the need for additional prospective trials.

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Improving Solute Clearances by Hemodialysis

Cited by 4 publications

References 98 publications

Physiologically based pharmacokinetic-pharmacodynamic evaluation of meropenem in CKD and hemodialysis individuals

Physiologically based pharmacokinetic-pharmacodynamic evaluation of meropenem in CKD and hemodialysis individuals

Displacing the Burden: A Review of Protein-Bound Uremic Toxin Clearance Strategies in Chronic Kidney Disease

Proceedings of the 2022 UAB CRRT Academy: Non-Invasive Hemodynamic Monitoring to Guide Fluid Removal with CRRT and Proliferation of Extracorporeal Blood Purification Devices

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