A randomized controlled trial of alanyl-glutamine supplementation in peritoneal dialysis fluid to assess impact on biomarkers of peritoneal health

Vychytil, Andreas; Herzog, Rebecca; Probst, Paul; Ribitsch, Werner; Lhotta, Karl; Machold-Fabrizii, Veronika; Wiesholzer, Martin; Kaufmann, Michaela; Salmhofer, Hermann; Windpessl, Martin; Rosenkranz, Alexander R.; Oberbauer, Rainer; König, Franz; Kratochwill, Klaus; Aufricht, Christoph

doi:10.1016/j.kint.2018.08.031

Cited by 36 publications

(47 citation statements)

References 49 publications

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“…The 24 mM AlaGln reduced 10 kDa and 70 kDa dextran transport to (32 ± 0.7) % and (61 ± 38) % of medium (p = 0.001/0.008). Based on these findings and since effects on cellular stress response in vitro [23,49] and on peritoneal transport in PD patients [27] were studied with 8 mM AlaGln, as higher doses of 10 kDa and 70 kDa dextran transport across the endothelial barrier was dose dependently reduced with AlaGln. After four hours, 8 mM AlaGln added to medium decreased 70 kDa transport across the endothelial barrier (p = 0.03), 10 kDa transport was unchanged (p = 0.15; Table 1).…”

Section: Alagln Increases Transepithelial Resistance and Reduces 10 Kmentioning

confidence: 99%

“…The 24 mM AlaGln reduced 10 kDa and 70 kDa dextran transport to (32 ± 0.7) % and (61 ± 38) % of medium (p = 0.001/0.008). Based on these findings and since effects on cellular stress response in vitro [23,49] and on peritoneal transport in PD patients [27] were studied with 8 mM AlaGln, as higher doses of AlaGln in the clinical setting may be associated with no benefit [50], this concentration was used throughout subsequent experiments. Addition of 8 mM AlaGln to conventional PD fluid (CPDF) and low GDP PD fluid (LPDF) increased TER after 1 and 5 h compared to CPDF and LPDF only (Table 1, Figure 2A).…”

Section: Alagln Increases Transepithelial Resistance and Reduces 10 Kmentioning

confidence: 99%

“…Addition of 8 mM AlaGln to CPDF during a single 4 h dwell in patients on chronic PD suggested restoration of peritoneal cellular stress responses, attenuation of sterile inflammation, and improved peritoneal host defense [26]. A subsequent randomized crossover study, using 8 mM AlaGln supplemented double chamber PD fluid over 8 weeks demonstrated higher CA-125 effluent concentrations, a marker of mesothelial cell viability, improved ex vivo (LPS and Pam 3 Cys) stimulated IL-6 release from effluent cells, and significantly improved peritoneal membrane semipermeability, i.e., higher dialytic removal of phosphate, uric acid, and potassium together with 20% lower peritoneal protein leakage [27].…”

Section: Introductionmentioning

confidence: 96%

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Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid

et al. 2020

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Understanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) efficacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein loss in a recent clinical trial. Transepithelial resistance and 10 kDa and 70 kDa dextran transport were measured in primary human endothelial cells (HUVEC) exposed to conventional acidic, glucose degradation products (GDP) containing PDF (CPDF) and to low GDP containing PDF (LPDF) with and without AlaGln. Zonula occludens-1 (ZO-1) and claudin-5 were quantified by Western blot and immunofluorescence and in mice exposed to saline and CPDF for 7 weeks by digital imaging analyses. Spatial clustering of ZO-1 molecules was assessed by single molecule localization microscopy. AlaGln increased transepithelial resistance, and in CPDF exposed HUVEC decreased dextran transport rates and preserved claudin-5 and ZO-1 abundance. Endothelial clustering of membrane bound ZO-1 was higher in CPDF supplemented with AlaGln. In mice, arteriolar endothelial claudin-5 was reduced in CPDF, but restored with AlaGln, while mesothelial claudin-5 abundance was unchanged. AlaGln supplementation seals the peritoneal endothelial barrier, and when supplemented to conventional PD fluid increases claudin-5 and ZO-1 abundance and clustering of ZO-1 in the endothelial cell membrane.

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Section: Alagln Increases Transepithelial Resistance and Reduces 10 Kmentioning

confidence: 99%

“…The 24 mM AlaGln reduced 10 kDa and 70 kDa dextran transport to (32 ± 0.7) % and (61 ± 38) % of medium (p = 0.001/0.008). Based on these findings and since effects on cellular stress response in vitro [23,49] and on peritoneal transport in PD patients [27] were studied with 8 mM AlaGln, as higher doses of AlaGln in the clinical setting may be associated with no benefit [50], this concentration was used throughout subsequent experiments. Addition of 8 mM AlaGln to conventional PD fluid (CPDF) and low GDP PD fluid (LPDF) increased TER after 1 and 5 h compared to CPDF and LPDF only (Table 1, Figure 2A).…”

Section: Alagln Increases Transepithelial Resistance and Reduces 10 Kmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid

et al. 2020

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“…In this issue of Kidney International Vychytil and colleagues investigate the addition of alanylglutamine (AlaGln) to biocompatible peritoneal dialysis fluids with the objective of improving markers of mesothelial cell health (4). This approach extends the existing concept of biocompatibility by replacing deficient glutamine in order to restore dysfunctional mesothelial cellular stress responses (Figure left panel).…”

Section: The Potential Benefits Of Alanyl-glutamine Supplementationmentioning

confidence: 99%

Does alanyl-glutamine supplementation offer potential to improve peritoneal dialysate biocompatibility?

Wilkie

Davies

2018

Kidney International

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“…In einer kürzlich beendeten, randomisierten, kontrollierten und doppelt verblindeten Phase-II-Studie mit Crossover-Design [43]…”

Section: Placebokontrollierte Studieunclassified

Biokompatible Peritonealdialyselösungen

Vychytil

2018

Dialyse aktuell

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ZusammenfassungDurch langzeitige intraperitoneale Anwendung von Glukoselösungen treten bei PD-Patienten (PD: Peritonealdialyse) morphologische und funktionelle Schäden an der Peritonealmembran auf. Es gibt keine eindeutige Evidenz, dass PD-Lösungen mit alternativen osmotischen Substanzen (Icodextrin, Aminosäuren) langfristig einen günstigen Einfluss auf peritonealeSchäden bei chronischen PD-Patienten haben. Dennoch ist die klinische Bedeutung von icodextrinhaltigen PD-Lösungen zur Optimierung des Salz- und Wasserhaushaltes uneingeschränkt. In rezenten Metaanalysen haben Low-GDP-Lösungen (GDP: Glukosedegradationsprodukte) harte Endpunkte wie Peritonitis und technisches Versagen nicht signifikant beeinflusst. Dennoch weisen einzelne kleinere Studien und Kohortenstudien darauf hin, dass diese Lösungen morphologische Schäden der Peritonealmembran reduzieren. Alanyl-Glutamin als Zusatz zur PD-Lösung hat in ersten klinischen Studien zu membranprotektiven, immunmodulatorischen und antiinflammatorischen Effekten geführt. Klinische Studien mit längerer Beobachtungszeit müssen zeigen, ob dies auch mit einer verbesserten Peritonitisrate, einem verbesserten technischen Überleben und/oder Überleben von PD-Patienten assoziiert ist.

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A randomized controlled trial of alanyl-glutamine supplementation in peritoneal dialysis fluid to assess impact on biomarkers of peritoneal health

Cited by 36 publications

References 49 publications

Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid

Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid

Does alanyl-glutamine supplementation offer potential to improve peritoneal dialysate biocompatibility?

Biokompatible Peritonealdialyselösungen

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