Development of Toxic Degradation Products during Heat Sterilization of Glucose-Containing Fluids for Peritoneal Dialysis: Influence of Time and Temperature

Kjellstrand, Per; Martinson, E. E.; Wieslander, Anders; Holmquist, Björn

doi:10.1177/089686089501500106

Cited by 62 publications

(31 citation statements)

References 27 publications

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“…Our results demonstrate that both 5-HMF and 2-FA are present in varying quantities in all injectable glucose solutions currently on the French market. Differences from one supplier to another may be explained by different sterilising processes (temperature, pressure and time of sterilization cycle) 1 , 6 , 35 , 36 . All suppliers confirmed the use of the moist heat method according to the European Pharmacopeia, but some did not provide their protocols.…”

Section: Discussionmentioning

confidence: 99%

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Factors Generating Glucose Degradation Products In Sterile Glucose Solutions For Infusion: Statistical Relevance Determination Of Their Impacts

Haybrard¹,

Simon²,

Danel³

et al. 2017

Sci Rep

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Sterilising glucose solutions by heat promotes the generation of a large number of glucose degradation products (GDPs). It has been shown that high levels of GDPs may result in Advanced Glycation End products that have an impact on cellular homeostasis and health in general. If data is available for peritoneal dialysis solutions, little has been published for glucose infusion fluids. It is essential to identify the parameters causing the formation of GDPs and so limit the risk of exposing patients to them. After quantifying both 5-hydroxymethyl-2-furfural, considered as an important indicator of degradation, and 2-furaldehyde, an ultimate GDP of one degradation pathway, in marketed solutions, the aim of this work is to build a model integrating all the parameters involved in the formation rates of these two GDPs: supplier, glucose amount, container material, oxygen permeability coefficient and time-lapse since manufacture. Our results show a good logarithmic relationship between GDP formation rates and time-lapse since manufacture for both GDPs. The amount of GDPs in the glucose solutions for infusion depends on the initial glucose amount, the polymer of the container, the time elapsed since manufacturing and the supplier.

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Section: Discussionmentioning

confidence: 99%

“…Kjellstrand et al . studied five different F 0 values and demonstrated that combining a high temperature with a short sterilisation time limited the formation of GDPs 36 . In our study, only one condition was close to those studied by Cook et al .…”

Section: Discussionmentioning

confidence: 99%

Factors Generating Glucose Degradation Products In Sterile Glucose Solutions For Infusion: Statistical Relevance Determination Of Their Impacts

Haybrard¹,

Simon²,

Danel³

et al. 2017

Sci Rep

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“…The process is substantially accelerated by exposure to high ambient temperatures. As commercially available PDF is heat sterilized, the degradation of PDF glucose occurs primarily during autoclaving and to a lesser extent also during prolonged storage (10–12). On the other hand, if PDF is sterilized by filtration, the levels of GDP generated are greatly diminished (13–15).…”

Section: Studies On the Role Of Glucose Degradation Products In Pdf Bmentioning

confidence: 99%

Continuous Flow Peritoneal Dialysis: Solution Formulation and Biocompatibility

Passlick–Deetjen

Lage

Jörres

2001

Seminars in Dialysis

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When peritoneal dialysis was introduced several years ago an important alternative dialysis therapy to hemodialysis was made available for the treatment of end-stage chronic disease. However, a continuous search for new developments and technologies is necessary to find the optimal peritoneal dialysis fluid (PDF) to preserve peritoneal membrane function as long as possible. Conventional PDFs are known to compromise the functional integrity of the peritoneal membrane as a consequence of their acidic pH in combination with their high lactate content, as well as the high concentrations of glucose and glucose degradation products (GDPs) present in currently used conventional solutions. Novel solutions such as bicarbonate-buffered PDF (at neutral pH) display improved in vitro biocompatibility as compared to conventional, acidic lactate-buffered PDF. Since these novel solutions are manufactured in dual-chambered bags they also contain fewer GDPs, thus further reducing their potential toxicity and protein glycation. Clinically the novel solutions reduce inflow pain and improve peritoneal membrane transport characteristics, ultrafiltration capacity, and effluent markers of peritoneal membrane integrity. The concept of continuous flow peritoneal dialysis (CFPD) is another approach to optimize PDF. The technique of CFPD not only enables the individualization of acid-base correction by variable concentrations of HCO3- but may also help to restore peritoneal cell functions by neutral pH, reduced glucose load, diminished GDP content, and reduced advanced glycation end product (AGE) formation, thereby potentially contributing to the improved preservation of peritoneal membrane function.

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“…In particular, PD patients are exposed to hypertonic glucose solution on a long-term basis, which is not only toxic to mesothelial cells[ 6 , 71 ] but also promotes immune cell apoptosis[ 72 ]. Moreover, the high-temperature sterilization process produces GDPs such as methylglyoxal (MGO), acetaldehyde, formaldehyde, and 3-deoxyglucosone in PD dialysate[ 73 - 76 ]. GDPs possess strong oxidative properties and toxicity, and can induce AGEs[ 77 ].…”

Section: High Glucose and Gdp Increase Osmentioning

confidence: 99%

Targeting cannabinoid signaling for peritoneal dialysis-induced oxidative stress and fibrosis

Yang

Chau

Chen

et al. 2017

WJN

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Long-term exposure to bioincompatible peritoneal dialysis (PD) solutions frequently results in peritoneal fibrosis and ultrafiltration failure, which limits the life-long use of and leads to the cessation of PD therapy. Therefore, it is important to elucidate the pathogenesis of peritoneal fibrosis in order to design therapeutic strategies to prevent its occurrence. Peritoneal fibrosis is associated with a chronic inflammatory status as well as an elevated oxidative stress (OS) status. Beyond uremia per se, OS also results from chronic exposure to high glucose load, glucose degradation products, advanced glycation end products, and hypertonic stress. Therapy targeting the cannabinoid (CB) signaling pathway has been reported in several chronic inflammatory diseases with elevated OS. We recently reported that the intra-peritoneal administration of CB receptor ligands, including CB1 receptor antagonists and CB2 receptor agonists, ameliorated dialysis-related peritoneal fibrosis. As targeting the CB signaling pathway has been reported to be beneficial in attenuating the processes of several chronic inflammatory diseases, we reviewed the interaction among the cannabinoid system, inflammation, and OS, through which clinicians ultimately aim to prolong the peritoneal survival of PD patients.

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Development of Toxic Degradation Products during Heat Sterilization of Glucose-Containing Fluids for Peritoneal Dialysis: Influence of Time and Temperature

Cited by 62 publications

References 27 publications

Factors Generating Glucose Degradation Products In Sterile Glucose Solutions For Infusion: Statistical Relevance Determination Of Their Impacts

Factors Generating Glucose Degradation Products In Sterile Glucose Solutions For Infusion: Statistical Relevance Determination Of Their Impacts

Continuous Flow Peritoneal Dialysis: Solution Formulation and Biocompatibility

Targeting cannabinoid signaling for peritoneal dialysis-induced oxidative stress and fibrosis

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