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Molecular Advances in Peritoneal Dialysis

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 6451

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Dr. Mario Bonomini

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Nephrology and Dialysis Institute, Department of Medicine, G. d’Annunzio University, Chieti-Pescara, SS. Annunziata Hospital, Via dei Vestini, 66013 Chieti, Italy
Interests: chronic kidney disease; dialysis; proteomics; red blood cells; end-stage renal disease; uremic toxins; selenium; nutritional molecules
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Dear Colleagues,

The increasing worldwide number of patients suffering from end-stage kidney failure (ESKF) who require a chronic renal replacement therapy represents a significant economic burden on health systems globally. Peritoneal dialysis (PD) represents a well-established, cost-effective treatment modality for ESKF that can be delivered at home. Compared with hemodialysis, PD offers a similar survival rate and is less expensive; in addition, it preserves residual kidney function better and removes solutes and fluid more gradually. The recent COVID-19 pandemic has highlighted the need for enhanced domiciliary care for ESKF patients. However, despite PD being a viable treatment for ESKF patients, it is still underprescribed. To a significant extent, this discrepancy can be explained by major limitations regarding PD efficiency and sustainability. In the short- and mid-term, infectious complications (primarily peritonitis) and catheter problems are the main reasons why this technique gets neglected. For patients on long-term PD, bio-incompatibility of the dialysis fluid represents a crucial problem. Furthermore, there is an unmet need for biomarkers as tools to identify patients who are at risk of PD-related complications and to guide personalized interventions. This issue aims to provide an update on the most recent molecular advances to improve the clinical outcomes of PD. Papers on molecular-level results are highly encouraged - papers that are more on the clinical side are not preferable.

Dr. Mario Bonomini
Guest Editor

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Keywords

peritoneal dialysis
peritoneal solution
technique
catheter
clinical outcome
advances
fibrosis
remote control
ultrafiltration
glucose sparing

Published Papers (5 papers)

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Research

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13 pages, 865 KiB

Open AccessArticle

Associations of Glucometabolic Indices with Aortic Stiffness in Patients Undergoing Peritoneal Dialysis with and without Diabetes Mellitus

by Chi-Chong Tang, Jen-Pi Tsai, Yi-Hsin Chen, Szu-Chun Hung, Yu-Li Lin and Bang-Gee Hsu

Int. J. Mol. Sci. 2023, 24(23), 17094; https://doi.org/10.3390/ijms242317094 - 04 Dec 2023

Cited by 1 | Viewed by 678

Abstract

Disruptions in glucose metabolism are frequently observed among patients undergoing peritoneal dialysis (PD) who utilize glucose-containing dialysis solutions. We aimed to investigate the relationship between glucometabolic indices, including fasting glucose, insulin resistance, advanced glycation end products (AGEs), PD-related glucose load, and icodextrin usage, and aortic stiffness in PD patients with and without diabetic mellitus (DM). This study involved 172 PD patients (mean age 58.3 ± 13.5 years), consisting of 110 patients without DM and 62 patients with DM. Aortic stiffness was assessed using the carotid-femoral pulse wave velocity (cfPWV). Impaired fasting glucose was defined as a fasting glucose level ≥ 100 mg/dL. Homeostatic model assessment for insulin resistance (HOMA-IR) scores, serum AGEs, dialysate glucose load, and icodextrin usage were assessed. Patients with DM exhibited the highest cfPWV (9.9 ± 1.9 m/s), followed by those with impaired fasting glucose (9.1 ± 1.4 m/s), whereas patients with normal fasting glucose had the lowest cfPWV (8.3 ± 1.3 m/s), which demonstrated a significant trend. In non-DM patients, impaired fasting glucose (β = 0.52, 95% confidence interval [CI] = 0.01–1.03, p = 0.046), high HOMA-IR (β = 0.60, 95% CI = 0.12–1.08, p = 0.015), and a high PD glucose load (β = 0.58, 95% CI = 0.08–1.08, p = 0.023) were independently associated with increased cfPWV. In contrast, none of the glucometabolic factors contributed to differences in cfPWV in DM patients. In conclusion, among PD patients without DM, impaired fasting glucose, insulin resistance, and PD glucose load were closely associated with aortic stiffness. Full article

(This article belongs to the Special Issue Molecular Advances in Peritoneal Dialysis)

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12 pages, 5058 KiB

Open AccessArticle

Molecular Dynamics Simulations of Ion Transport through Protein Nanochannels in Peritoneal Dialysis

by Jie Liu, Tao Zhang and Shuyu Sun

Int. J. Mol. Sci. 2023, 24(12), 10074; https://doi.org/10.3390/ijms241210074 - 13 Jun 2023

Cited by 1 | Viewed by 977

Abstract

In recent decades, the development of dialysis techniques has greatly improved the survival rate of renal failure patients, and peritoneal dialysis is gradually showing dominance over hemodialysis. This method relies on the abundant membrane proteins in the peritoneum, avoiding the use of artificial semipermeable membranes, and the ion fluid transport is partly controlled by the protein nanochannels. Hence, this study investigated ion transport in these nanochannels by using molecular dynamics (MD) simulations and an MD Monte Carlo (MDMC) algorithm for a generalized protein nanochannel model and a saline fluid environment. The spatial distribution of ions was determined via MD simulations, and it agreed with that modeled via the MDMC method; the effects of simulation duration and external electronic fields were also explored to validate the MDMC algorithm. The specific atomic sequence within a nanochannel was visualized, which was the rare transport state during the ion transport process. The residence time was assessed through both methods to represent the involved dynamic process, and its values showed the temporal sequential order of different components in the nanochannel as follows: H₂O > Na⁺ > Cl⁻. The accurate prediction using the MDMC method of the spatial and temporal properties proves its suitability to handle ion transport problems in protein nanochannels. Full article

(This article belongs to the Special Issue Molecular Advances in Peritoneal Dialysis)

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14 pages, 1405 KiB

Open AccessArticle

Fibrosis of Peritoneal Membrane, Molecular Indicators of Aging and Frailty Unveil Vulnerable Patients in Long-Term Peritoneal Dialysis

by Patrícia Branco, Rita Calça, Ana Rita Martins, Catarina Mateus, Maria João Jervis, Daniel Pinto Gomes, Sofia Azeredo-Lopes, Antonio Ferreira De Melo Junior, Cátia Sousa, Ester Civantos, Sebastian Mas-Fontao, Augusta Gaspar, Sância Ramos, Judit Morello, Fernando Nolasco, Anabela Rodrigues and Sofia Azeredo Pereira

Int. J. Mol. Sci. 2023, 24(5), 5020; https://doi.org/10.3390/ijms24055020 - 06 Mar 2023

Cited by 2 | Viewed by 1833

Abstract

Peritoneal membrane status, clinical data and aging-related molecules were investigated as predictors of long-term peritoneal dialysis (PD) outcomes. A 5-year prospective study was conducted with the following endpoints: (a) PD failure and time until PD failure, (b) major cardiovascular event (MACE) and time until MACE. A total of 58 incident patients with peritoneal biopsy at study baseline were included. Peritoneal membrane histomorphology and aging-related indicators were assessed before the start of PD and investigated as predictors of study endpoints. Fibrosis of the peritoneal membrane was associated with MACE occurrence and earlier MACE, but not with the patient or membrane survival. Serum α-Klotho bellow 742 pg/mL was related to the submesothelial thickness of the peritoneal membrane. This cutoff stratified the patients according to the risk of MACE and time until MACE. Uremic levels of galectin-3 were associated with PD failure and time until PD failure. This work unveils peritoneal membrane fibrosis as a window to the vulnerability of the cardiovascular system, whose mechanisms and links to biological aging need to be better investigated. Galectin-3 and α-Klotho are putative tools to tailor patient management in this home-based renal replacement therapy. Full article

(This article belongs to the Special Issue Molecular Advances in Peritoneal Dialysis)

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9 pages, 1163 KiB

Open AccessCommunication

pH Gradient Liposomes Extract Protein Bound Amitriptyline in Peritoneal Dialysis—Exploratory Work

by Grant Cave, Rachel Kee, Martyn Harvey and Zimei Wu

Int. J. Mol. Sci. 2022, 23(19), 11577; https://doi.org/10.3390/ijms231911577 - 30 Sep 2022

Cited by 1 | Viewed by 1665

Abstract

Poisoning is a significant cause of injury-related death worldwide. Dialysis is usually ineffective in removing the toxin once it has been absorbed because of drug protein binding and high volumes of distribution. In this work, we explore whether the addition of liposomes to peritoneal dialysate could extract protein bound amitriptyline. Liposomes were prepared using the thin film hydration method. In the in vitro experiment, 3 mL of 20% albumin with a concentration of 6000 nmol/L amitriptyline in a proprietary dialysis cartridge was dialysed against 125 mL of phosphate-buffered saline with and without 80 mg 1,2-dioleoyl-sn-glycero-3-phosphoglycerol (DOPG) liposomes. In the in vivo arm, peritoneal dialysis was undertaken in 6 rats with pH gradient liposome augmented dialysate after intravenous amitriptyline injection. Peritoneal blood flow was estimated by CO₂ extraction. Total amitriptyline extracted was compared to freely dissolved (non-protein bound) and total amitriptyline perfusing the membrane during the peritoneal dwell. Mean liposome size for DOPG and acidic centre pH gradient liposomes was 119 nm and 430 nm, respectively. In the in vitro experiment, more amitriptyline was extracted into the liposome containing dialysate than the control dialysate (40 +/− 2 nmol/L vs. 27 +/− 1 nmol/L). In the in vivo experiment, the total amitriptyline in dialysate was 5240 +/− 2750 nmol. Mean total free amitriptyline perfusing the peritoneal membrane was 93 +/− 46 nmol. Mean total blood amitriptyline perfusing the peritoneal membrane was 23,920 +/− 6920 nmol. Two of the six animals were excluded due to overestimation of peritoneal blood flow. This exploratory work suggests the addition of liposome nanoparticles to peritoneal dialysate extracted protein bound amitriptyline from blood. Full article

(This article belongs to the Special Issue Molecular Advances in Peritoneal Dialysis)

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Review

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24 pages, 367 KiB

Open AccessReview

Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge

by Mario Bonomini, Valentina Masola, Maria Pia Monaco, Vittorio Sirolli, Lorenzo Di Liberato, Tommaso Prosdocimi and Arduino Arduini

Int. J. Mol. Sci. 2024, 25(6), 3532; https://doi.org/10.3390/ijms25063532 - 20 Mar 2024

Viewed by 586

Abstract

Peritoneal dialysis (PD) is a home-based efficacious modality for the replacement of renal function in end-stage kidney failure patients, but it is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of the long-term morpho-functional peritoneal changes that eventually result in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile is proving to be quite difficult. New approaches targeting the composition of the PD solution include the replacement of glucose with other osmotic agents, and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include the infusion of mesenchymal cells or the administration of orally active agents. In the present article, we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD). Full article

(This article belongs to the Special Issue Molecular Advances in Peritoneal Dialysis)

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