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- Bonomini, M, et al.
(författare)
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The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis
- 2021
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Ingår i: Journal of nephrology. - : Springer Science and Business Media LLC. - 1724-6059 .- 1121-8428. ; 34:2, s. 503-519
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Tidskriftsartikel (refereegranskat)abstract
- Peritoneal dialysis (PD) is a viable but under-prescribed treatment for uremic patients. Concerns about its use include the bio-incompatibility of PD fluids, due to their potential for altering the functional and anatomical integrity of the peritoneal membrane. Many of these effects are thought to be due to the high glucose content of these solutions, with attendant issues of products generated during heat treatment of glucose-containing solutions. Moreover, excessive intraperitoneal absorption of glucose from the dialysate has many potential systemic metabolic effects. This article reviews the efforts to develop alternative PD solutions that obviate some of these side effects, through the replacement of part of their glucose content with other osmolytes which are at least as efficient in removing fluids as glucose, but less impactful on patient metabolism. In particular, we will summarize clinical studies on the use of alternative osmotic ingredients that are commercially available (icodextrin and amino acids) and preclinical studies on alternative solutions under development (taurine, polyglycerol, carnitine and xylitol). In addition to the expected benefit of a glucose-sparing approach, we describe an ‘osmo-metabolic’ approach in formulating novel PD solutions, in which there is the possibility of exploiting the pharmaco-metabolic properties of some of the osmolytes to attenuate the systemic side effects due to glucose. This approach has the potential to ameliorate pre-existing co-morbidities, including insulin resistance and type-2 diabetes, which have a high prevalence in the dialysis population, including in PD patients.
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- Bonomini, M, et al.
(författare)
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How to Improve the Biocompatibility of Peritoneal Dialysis Solutions (without Jeopardizing the Patient's Health)
- 2021
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:15
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Tidskriftsartikel (refereegranskat)abstract
- Peritoneal dialysis (PD) is an important, if underprescribed, modality for the treatment of patients with end-stage kidney disease. Among the barriers to its wider use are the deleterious effects of currently commercially available glucose-based PD solutions on the morphological integrity and function of the peritoneal membrane due to fibrosis. This is primarily driven by hyperglycaemia due to its effects, through multiple cytokine and transcription factor signalling—and their metabolic sequelae—on the synthesis of collagen and other extracellular membrane components. In this review, we outline these interactions and explore how novel PD solution formulations are aimed at utilizing this knowledge to minimise the complications associated with fibrosis, while maintaining adequate rates of ultrafiltration across the peritoneal membrane and preservation of patient urinary volumes. We discuss the development of a new generation of reduced-glucose PD solutions that employ a variety of osmotically active constituents and highlight the biochemical rationale underlying optimization of oxidative metabolism within the peritoneal membrane. They are aimed at achieving optimal clinical outcomes and improving the whole-body metabolic profile of patients, particularly those who are glucose-intolerant, insulin-resistant, or diabetic, and for whom daily exposure to high doses of glucose is contraindicated.
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- Rago, C, et al.
(författare)
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A New Peritoneal Dialysis Solution Containing L-Carnitine and Xylitol for Patients on Continuous Ambulatory Peritoneal Dialysis: First Clinical Experience
- 2021
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Ingår i: Toxins. - : MDPI AG. - 2072-6651. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Peritoneal dialysis (PD) is a feasible and effective renal replacement therapy (RRT) thanks to the dialytic properties of the peritoneal membrane (PM). Preservation of PM integrity and transport function is the key to the success of PD therapy, particularly in the long term, since the prolonged exposure to unphysiological hypertonic glucose-based PD solutions in current use is detrimental to the PM, with progressive loss of peritoneal ultrafiltration capacity causing technique failure. Moreover, absorbing too much glucose intraperitoneally from the dialysate may give rise to a number of systemic metabolic effects. Here we report the preliminary results of the first clinical experience based on the use in continuous ambulatory PD (CAPD) patients of novel PD solutions obtained through partly replacing the glucose load with other osmotically active metabolites, such as L-carnitine and xylitol. Ten CAPD patients were treated for four weeks with the new solutions. There was good tolerance to the experimental PD solutions, and no adverse safety signals were observed. Parameters of dialysis efficiency including creatinine clearance and urea Kt/V proved to be stable as well as fluid status, diuresis, and total peritoneal ultrafiltration. The promising tolerance and local/systemic advantages of using L-carnitine and xylitol in the PD solution merit further research.
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