Biological Significance of Reducing Glucose Degradation Products in Peritoneal Dialysis Fluids

Abstract

Carbohydrates are not stable when exposed to energy; they degrade into new molecules. In peritoneal dialysis (PD) fluids, degradation of glucose occurs during the heat sterilization procedure. The biological consequences of this degradation are side effects such as impaired proliferation and impaired host defense mechanisms, demonstrated in vitro for a great variety of cells. Several highly toxic compounds—such as formaldehyde and 3-deoxyglucosone—have been identified in PD fluids. Carbonyl compounds, apart from being cytotoxic, are also well-known promoters of irreversible advanced glycation end-products (AGEs), which might participate in the long-term remodeling of the peritoneal membrane. Various approaches can be used to reduce the formation of glucose degradation products (GDPs) during heat sterilization. Some examples are shortening the sterilization time, lowering the pH, removing catalyzing substances, and increasing glucose concentration. The latter three factors are employed in the multi-compartment bag with a separate chamber containing pure glucose at high concentration and low pH. Gambrosol trio, a PD fluid produced in this way, shows reduced cytotoxicity, normalized host defense reactions, less AGE formation, and reduced concentrations of formaldehyde and 3-deoxyglucosone. Moreover, in the clinical situation, the fluid turns out to be more biocompatible for the patient, causing less mesothelial cell damage, which in the long term could lead to a more intact peritoneal membrane. Conclusion Glucose degradation products in heat-sterilized fluids for peritoneal dialysis are cytotoxic, promote AGE formation, and cause negative side effects for the patient. Using improved and well-controlled manufacturing processes, it is possible to produce sterile PD fluids with glucose as the osmotic agent but without the negative side effects related to GDPs.

Evolving concepts on the age‐related changes in “muscle quality”

“…Theoretically, disruption at any point in the E-CC process can prevent optimal activation of muscle mass and thus reduce muscle quality. Impairments in SR Ca 2+ release have been suggested to explain deficits of muscle quality in aged muscle [192][193][194][195], and in this regard, the role of Osvaldo Delbono must be acknowledged. Arguably, the idea that changes in E-CC were contributing to age-related weakness began with his reports of "excitation-calcium release uncoupling" in single fibers from aged human muscles [196].…”

“…These proteins are both associated with the triadic junctions between the t-tubules and terminal cisternae, and both appear necessary for normal triad organization and optimal E–CC [ 214 – 218 ]. Interestingly, MG29 has been linked to SOCE and has been shown to decline with aging [ 191 , 195 ], and may contribute to the fragmentation of the SR, resulting in fragments of Ca 2+ -containing SR disconnected from the t-tubule membranes [ 219 ]. It has been hypothesized that this fragmentation occurs in a subpopulation of fibers that became at least partially dependent on extracellular Ca 2+ for SR Ca 2+ .…”

Alpha-1 antitrypsin inhibits formaldehyde-induced apoptosis of human peritoneal mesothelial cells

“…21 Thus, glucose in PD fluids breaks down into other molecules during the heat sterilization procedure. 22 GDPs are one of the most critical influences on the biocompatibility of glucose-based PD solutions. The concentrations of diverse GDPs differ depending on the temperature and pH during the sterilization and storage processes.…”

Effect of Benfotiamine in Podocyte Damage Induced by Peritoneal Dialysis Fluid

“…Glucose degradation products are a heterogeneous group of small molecular weight carbonyls formed within PDFs as a direct consequence of heat-sterilization ( 12 ). They exhibit a facile reactivity with various biomolecules, including proteins, DNA, and phospholipids, generating stable products, such as advanced glycation end-products (AGEs).…”