Contemporary and Emerging Modalities of Kidney Assistance Therapy for Patients with Kidney Dysfunction Requiring Dialysis

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Uremic Toxins".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 4417

Special Issue Editors


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Guest Editor
Department of Internal Medicine, Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA
Interests: extracorporeal kidney assistance therapy; individualized dialysis; individualized vascular access

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Guest Editor
1. Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
2. Medical Services, Ralph H. Johnson VA Medical Center, Charleston, SC 29401, USA
Interests: dialysis; CRRT; electrolytes; transplant
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Special Issue Information

Dear Colleagues,

Kidney assistance therapy is the cornerstone of treatment for kidney dysfunction requiring dialysis (KDRD) and focuses on uremic toxin removal and fluid regulation. Broadly, kidney assistance therapy can be divided into two categories: extracorporeal and intracorporeal.

Extracorporeal therapy is the most prevalent form of kidney assistance with core components consisting of a dialyzer and dialysis machine. Adjunctive elements like replacement fluids or sorbent technologies may modulate its functionality. Based on the configuration of these components, extracorporeal therapy can be classified into two main modalities: hemodialysis and hemodiafiltration. Each modality provides varying levels of uremic toxin clearance and employs distinct fluid management strategies. Hemodialysis primarily relies on diffusion for solute removal, targeting small and medium-sized toxins. Hemodiafiltration combines diffusion and convection, enhancing the clearance of larger molecular weight toxins while improving fluid balance. Adjunctive technologies, such as sorbent-based devices, are tools that can optimize uremic toxin removal.

Intracorporeal therapy, currently represented by peritoneal dialysis, involves the utilization of the patient’s peritoneal membrane as a natural filter. Core components include a peritoneal dialysis machine and dialysate. The effectiveness of this modality hinges on individual peritoneal membrane characteristics, which influence solute clearance and fluid removal.

In addition to the established extracorporeal and intracorporeal kidney assistance therapies, innovations hold promise for transforming the management of kidney dysfunction by improving portability, accessibility, and patient outcomes. These innovations include portable extracorporeal kidney assistance devices, implantable intracorporeal artificial kidneys, and intestinal dialysis.

In this Toxins Special Issue, we welcome manuscripts focusing on the core and adjunctive components of extracorporeal and intracorporeal kidney assistance therapies utilized for the chronic treatment of patients with KDRD. They will explore how kidney assistance technologies differ in their ability to address uremic toxin levels and fluid imbalances, providing insights into selecting appropriate techniques for individualized care. Additionally, papers will cover emerging innovations in kidney assistance, including portable devices, intestinal dialysis, and implantable therapies, offering a glimpse into future possibilities. The goal of this Special Issue is to empower clinicians with a deeper understanding of current and emerging technologies in kidney assistance therapy, enabling them to tailor treatments that evolve alongside patients’ biological and clinical conditions.

Dr. Mariana Murea
Prof. Dr. Tibor Fülöp
Guest Editors

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Keywords

  • uremic toxin
  • dialysis
  • dialyzer
  • filtration
  • intestinal
  • implantable
  • portable
  • sorbent

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Published Papers (3 papers)

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Research

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18 pages, 2349 KB  
Article
Comparing Computational Peritoneal Dialysis Models in Pigs and Patients
by Sangita Swapnasrita, Joost C. de Vries, Joanna Stachowska-Piętka, Carl M Öberg, Karin G. F. Gerritsen and Aurélie Carlier
Toxins 2025, 17(7), 329; https://doi.org/10.3390/toxins17070329 - 28 Jun 2025
Viewed by 861
Abstract
Computational models of peritoneal dialysis (PD) are increasingly useful for optimizing treatment in patients with kidney disease requiring dialysis (KDRD). However, although several mathematical models have been developed in the past few decades, a direct comparison of the models’ accuracy with respect to [...] Read more.
Computational models of peritoneal dialysis (PD) are increasingly useful for optimizing treatment in patients with kidney disease requiring dialysis (KDRD). However, although several mathematical models have been developed in the past few decades, a direct comparison of the models’ accuracy with respect to predicting in vivo data is needed to further create robust personalized models. Here, we used a dataset obtained in a previous in vivo experimental model of PD in pigs (23 sessions of 4 h 2 L dwells in four pigs) and humans (20 sessions in 20 patients) to compare six computational models of PD: the Graff model (UGM), the three-pore model (TPM), the Garred model (GM), and the Waniewski model (WM), as well as two variations of these (UGM-18, SWM). We conducted this comparison to predict the dialysate concentrations of key uremic toxins and electrolytes (four in humans) throughout a 4 h dwell. The model predictions can provide insight into inter-individual differences in ultrafiltration, which are critical for tailoring PD regimens in KDRD. While TPM offered improved physiological reality, its computational cost suggests a trade-off between model complexity and clinical applicability for real-time or portable kidney support systems. In future applications, such models could provide adaptive PD regimens for tailored care based on patient-specific toxin kinetics and fluid dynamics. Full article
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Review

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17 pages, 939 KB  
Review
Intermittent Infusion Hemodiafiltration: A Narrative Review of an Emerging Dialysis Modality
by Xiaoxi Zhou, Jing Sun and Lining Miao
Toxins 2025, 17(9), 442; https://doi.org/10.3390/toxins17090442 - 3 Sep 2025
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Abstract
The number of patients with end-stage renal disease continues to grow worldwide, placing increasing demands on dialysis technologies. Conventional hemodialysis remains the dominant modality but is often limited by frequent intradialytic hypotension and the insufficient removal of medium-sized toxins. Intermittent infusion hemodiafiltration (I-HDF) [...] Read more.
The number of patients with end-stage renal disease continues to grow worldwide, placing increasing demands on dialysis technologies. Conventional hemodialysis remains the dominant modality but is often limited by frequent intradialytic hypotension and the insufficient removal of medium-sized toxins. Intermittent infusion hemodiafiltration (I-HDF) is an emerging, hybrid dialysis technique that combines standard hemodialysis with the cyclic backfiltration of ultrapure dialysate. This approach enables dynamic blood volume control and periodic backflushing of the dialyzer membrane. Recent clinical studies demonstrate that I-HDF can reduce intradialytic hypotension incidence, improve systemic and microcirculatory perfusion, and enhance the clearance of middle molecules such as β2-microglobulin, while minimizing albumin loss. These benefits are particularly relevant to toxin clearance and hemodynamic stabilization, key priorities in optimizing dialysis outcomes. Large-scale cohort data suggest that I-HDF may be linked to improved long-term survival in dialysis patients. Given its physiological advantages and operational flexibility, I-HDF may also offer a practical solution in healthcare systems with limited access to high-volume online hemodiafiltration or kidney transplantation. Further research is warranted to develop individualized infusion protocols and validate its broader applicability. Full article
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20 pages, 335 KB  
Review
From Physicochemical Classification to Multidimensional Insights: A Comprehensive Review of Uremic Toxin Research
by Mario Cozzolino, Lorenza Magagnoli and Paola Ciceri
Toxins 2025, 17(6), 295; https://doi.org/10.3390/toxins17060295 - 10 Jun 2025
Cited by 2 | Viewed by 1949
Abstract
Chronic kidney disease (CKD) is a global health burden, with uremic toxins (UTs) playing a central role in its pathophysiology. In this review, we systematically examined the evolution of UT classification from the 2003 European Uremic Toxin Work Group (EUTox) system based on [...] Read more.
Chronic kidney disease (CKD) is a global health burden, with uremic toxins (UTs) playing a central role in its pathophysiology. In this review, we systematically examined the evolution of UT classification from the 2003 European Uremic Toxin Work Group (EUTox) system based on molecular weight and protein-binding properties to the 2023 multidimensional framework integrating clinical outcomes, clearance technologies, and artificial intelligence. We highlighted the toxicity mechanisms of UTs across the cardiovascular, immune, and nervous systems and evaluated traditional (e.g., low-/high-flux hemodialysis) and advanced (e.g., high-cutoff dialysis and hemoadsorption) clearance strategies. Despite progress, challenges persist in toxin detection, clearance efficiency, and personalized therapy. Future directions include multi-omics-based biomarker discovery, optimized dialysis membranes, advanced adsorption technology, and AI-driven treatment personalization. This synthesis aims to bridge translational gaps and guide precision medicine in nephrology. Full article
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