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Open Access 01-07-2010 | Original

Infusion fluids contain harmful glucose degradation products

Authors: Anna Bryland, Marcus Broman, Martin Erixon, Bengt Klarin, Torbjörn Lindén, Hans Friberg, Anders Wieslander, Per Kjellstrand, Claudio Ronco, Ola Carlsson, Gabriela Godaly

Published in: Intensive Care Medicine | Issue 7/2010

Abstract

Purpose

Glucose degradation products (GDPs) are precursors of advanced glycation end products (AGEs) that cause cellular damage and inflammation. We examined the content of GDPs in commercially available glucose-containing infusion fluids and investigated whether GDPs are found in patients’ blood.

Methods

The content of GDPs was examined in infusion fluids by high-performance liquid chromatography (HPLC) analysis. To investigate whether GDPs also are found in patients, we included 11 patients who received glucose fluids (standard group) during and after their surgery and 11 control patients receiving buffered saline (control group). Blood samples were analyzed for GDP content and carboxymethyllysine (CML), as a measure of AGE formation. The influence of heat-sterilized fluids on cell viability and cell function upon infection was investigated.

Results

All investigated fluids contained high concentrations of GDPs, such as 3-deoxyglucosone (3-DG). Serum concentration of 3-DG increased rapidly by a factor of eight in patients receiving standard therapy. Serum CML levels increased significantly and showed linear correlation with the amount of infused 3-DG. There was no increase in serum 3-DG or CML concentrations in the control group. The concentration of GDPs in most of the tested fluids damaged neutrophils, reducing their cytokine secretion, and inhibited microbial killing.

Conclusions

These findings indicate that normal standard fluid therapy involves unwanted infusion of GDPs. Reduction of the content of GDPs in commonly used infusion fluids may improve cell function, and possibly also organ function, in intensive-care patients.

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Iapichino G, Albicini M, Umbrello M, Sacconi F, Fermo I, Pavlovich R, Paroni R, Bellani G, Mistraletti G, Cugno M, Pesenti A, Gattinoni L (2008) Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients. Intensive Care Med 34:1843–1850CrossRefPubMed

Michalia M, Kompoti M, Koutsikou A, Paridou A, Giannopoulou P, Trikka-Graphakos E, Clouva-Molyvdas P (2009) Diabetes mellitus is an independent risk factor for ICU-acquired bloodstream infections. Intensive Care Med 35:448–454CrossRefPubMed

Preiser JC, Devos P, Ruiz-Santana S, Melot C, Annane D, Groeneveld J, Iapichino G, Leverve X, Nitenberg G, Singer P, Wernerman J, Joannidis M, Stecher A, Chiolero R (2009) A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med 35:1738–1748CrossRefPubMed

Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hebert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ (2009) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 360:1283–1297CrossRefPubMed

Wieslander AP, Nordin MK, Kjellstrand PT, Boberg UC (1991) Toxicity of peritoneal dialysis fluids on cultured fibroblasts, L-929. Kidney Int 40:77–79CrossRefPubMed

Linden T, Forsback G, Deppisch R, Henle T, Wieslander A (1998) 3-Deoxyglucosone, a promoter of advanced glycation end products in fluids for peritoneal dialysis. Perit Dial Int 18:290–293PubMed

Linden T, Cohen A, Deppisch R, Kjellstrand P, Wieslander A (2002) 3, 4-Dideoxyglucosone-3-ene (3, 4-DGE): a cytotoxic glucose degradation product in fluids for peritoneal dialysis. Kidney Int 62:697–703CrossRefPubMed

Conaway CC, Whysner J, Verna LK, Williams GM (1996) Formaldehyde mechanistic data and risk assessment: endogenous protection from DNA adduct formation. Pharmacol Ther 71:29–55CrossRefPubMed

Morgan LW, Wieslander A, Davies M, Horiuchi T, Ohta Y, Beavis MJ, Craig KJ, Williams JD, Topley N (2003) Glucose degradation products (GDP) retard remesothelialization independently of d-glucose concentration. Kidney Int 64:1854–1866CrossRefPubMed

10.

Justo P, Sanz AB, Egido J, Ortiz A (2005) 3, 4-Dideoxyglucosone-3-ene induces apoptosis in renal tubular epithelial cells. Diabetes 54:2424–2429CrossRefPubMed

11.

Catalan MP, Santamaria B, Reyero A, Ortiz A, Egido J, Ortiz A (2005) 3, 4-di-deoxyglucosone-3-ene promotes leukocyte apoptosis. Kidney Int 68:1303–1311CrossRefPubMed

12.

Erixon M, Wieslander A, Linden T, Carlsson O, Jönsson JÅ, Simonsen O, Kjellstrand P (2007) 3, 4-DGE in peritoneal dialysis fluids cannot be found in plasma after infusion into the peritoneal cavity. Perit Dial Int 28:277–278

13.

Zeier M, Schwenger V, Deppisch R, Haug U, Weigel K, Bahner U, Wanner C, Schneider H, Henle T, Ritz E (2003) Glucose degradation products in PD fluids: do they disappear from the peritoneal cavity and enter the systemic circulation? Kidney Int 63:298–305CrossRefPubMed

14.

Sarafidis PA, Whaley-Connell A, Sowers JR, Bakris GL (2006) Cardiometabolic syndrome and chronic kidney disease: what is the link? J Cardiometab Syndr 1:58–65CrossRefPubMed

15.

Lin CL, Wang FS, Kuo YR, Huang YT, Huang HC, Sun YC, Kuo YH (2006) Ras modulation of superoxide activates ERK-dependent fibronectin expression in diabetes-induced renal injuries. Kidney Int 69:1593–1600CrossRefPubMed

16.

Garcia-Lopez E, Carrero JJ, Suliman ME, Lindholm B, Stenvinkel P (2007) Risk factors for cardiovascular disease in patients undergoing peritoneal dialysis. Perit Dial Int 27 suppl 2:S205–209

17.

Erixon M, Wieslander A, Linden T, Carlsson O, Forsback G, Svensson E, Jonsson JA, Kjellstrand P (2005) Take care in how you store your PD fluids: actual temperature determines the balance between reactive and non-reactive GDPs. Perit Dial Int 25:583–590PubMed

18.

Erixon M, Wieslander A, Linden T, Carlsson O, Forsback G, Svensson E, Jonsson JA, Kjellstrand P (2006) How to avoid glucose degradation products in peritoneal dialysis fluids. Perit Dial Int 26:490–497PubMed

19.

Williams JD, Topley N, Craig KJ, Mackenzie RK, Pischetsrieder M, Lage C, Passlick-Deetjen J (2004) The Euro-Balance trial: the effect of a new biocompatible peritoneal dialysis fluid (balance) on the peritoneal membrane. Kidney Int 66:408–418CrossRefPubMed

20.

Schmitt CP, von Heyl D, Rieger S, Arbeiter K, Bonzel KE, Fischbach M, Misselwitz J, Pieper AK, Schaefer F (2007) Reduced systemic advanced glycation end products in children receiving peritoneal dialysis with low glucose degradation product content. Nephrol Dial Transplant 22:2038–2044CrossRefPubMed

21.

Rippe B, Simonsen O, Heimburger O, Christensson A, Haraldsson B, Stelin G, Weiss L, Nielsen FD, Bro S, Friedberg M, Wieslander A (2001) Long-term clinical effects of a peritoneal dialysis fluid with less glucose degradation products. Kidney Int 59:348–357CrossRefPubMed

22.

Montenegro J, Saracho R, Gallardo I, Martinez I, Munoz R, Quintanilla N (2007) Use of pure bicarbonate-buffered peritoneal dialysis fluid reduces the incidence of CAPD peritonitis. Nephrol Dial Transplant 22:1703–1708CrossRefPubMed

23.

Lee HY, Choi HY, Park HC, Seo BJ, Do JY, Yun SR, Song HY, Kim YH, Kim YL, Kim DJ, Kim YS, Kim MJ, Shin SK (2006) Changing prescribing practice in CAPD patients in Korea: increased utilization of low GDP solutions improves patient outcome. Nephrol Dial Transplant 21:2893–2899CrossRefPubMed

24.

Wieslander AP, Andren AH, Nilsson-Thorell C, Muscalu N, Kjellstrand PT, Rippe B (1995) Are aldehydes in heat-sterilized peritoneal dialysis fluids toxic in vitro? Perit Dial Int 15:348–352PubMed

25.

Ulbricht RJ, Northup SJ, Thomas JA (1984) A review of 5-hydroxymethylfurfural (HMF) in parenteral solutions. Fundam Appl Toxicol 4:843–853CrossRefPubMed

26.

Kusunoki H, Miyata S, Ohara T, Liu BF, Uriuhara A, Kojima H, Suzuki K, Miyazaki H, Yamashita Y, Inaba K, Kasuga M (2003) Relation between serum 3-deoxyglucosone and development of diabetic microangiopathy. Diabetes Care 26:1889–1894CrossRefPubMed

27.

Humpert PM, Lukic IK, Thorpe SR, Hofer S, Awad EM, Andrassy M, Deemer EK, Kasper M, Schleicher E, Schwaninger M, Weigand MA, Nawroth PP, Bierhaus A (2009) AGE-modified albumin containing infusion solutions boosts septicaemia and inflammation in experimental peritonitis. J Leukoc Biol 86:589–597CrossRefPubMed

28.

Agalou S, Ahmed N, Thornalley PJ, Dawnay A (2005) Advanced glycation end product free adducts are cleared by dialysis. Ann NY Acad Sci 1043:734–739CrossRefPubMed

29.

Agalou S, Ahmed N, Babaei-Jadidi R, Dawnay A, Thornalley PJ (2005) Profound mishandling of protein glycation degradation products in uremia and dialysis. J Am Soc Nephrol 16:1471–1485CrossRefPubMed

30.

Simm A, Wagner J, Gursinsky T, Nass N, Friedrich I, Schinzel R, Czeslik E, Silber RE, Scheubel RJ (2007) Advanced glycation endproducts: a biomarker for age as an outcome predictor after cardiac surgery? Exp Gerontol 42:668–675CrossRefPubMed

31.

Franke S, Muller A, Sommer M, Busch M, Kientsch-Engel R, Stein G (2003) Serum levels of total homocysteine, homocysteine metabolites and of advanced glycation end-products (AGEs) in patients after renal transplantation. Clin Nephrol 59:88–97PubMed

32.

Brown TR, Su B, Brown KA, Schwartz MA, Tobia AM, Kappler F (2003) Modulation of in vivo 3-deoxyglucosone levels. Biochem Soc Trans 31:1433–1437CrossRefPubMed

33.

Costa S, Coelho P, Costa C, Silva S, Mayan O, Santos LS, Gaspar J, Teixeira JP (2008) Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde. Toxicology 252:40–48CrossRefPubMed

34.

Zwart A, Woutersen RA, Wilmer JW, Spit BJ, Feron VJ (1988) Cytotoxic and adaptive effects in rat nasal epithelium after 3-day and 13-week exposure to low concentrations of formaldehyde vapour. Toxicology 51:87–99CrossRefPubMed

35.

Williams ME (2006) New potential agents in treating diabetic kidney disease: the fourth act. Drugs 66:2287–2298CrossRefPubMed

36.

Chetyrkin SV, Zhang W, Hudson BG, Serianni AS, Voziyan PA (2008) Pyridoxamine protects proteins from functional damage by 3-deoxyglucosone: mechanism of action of pyridoxamine. Biochemistry 47:997–1006CrossRefPubMed

37.

Nakamura S, Li H, Adijiang A, Pischetsrieder M, Niwa T (2007) Pyridoxal phosphate prevents progression of diabetic nephropathy. Nephrol Dial Transplant 22:2165–2174CrossRefPubMed

38.

Alderson NL, Chachich ME, Youssef NN, Beattie RJ, Nachtigal M, Thorpe SR, Baynes JW (2003) The AGE inhibitor pyridoxamine inhibits lipemia and development of renal and vascular disease in Zucker obese rats. Kidney Int 63:2123–2133CrossRefPubMed

39.

Muellenbach EA, Diehl CJ, Teachey MK, Lindborg KA, Archuleta TL, Harrell NB, Andersen G, Somoza V, Hasselwander O, Matuschek M, Henriksen EJ (2008) Interactions of the advanced glycation end product inhibitor pyridoxamine and the antioxidant alpha-lipoic acid on insulin resistance in the obese Zucker rat. Metabolism 57:1465–1472CrossRefPubMed

40.

Berstein LM, Vasilyev DA, Poroshina TE, Kovalenko IG (2006) Glucose-induced effects and joker function of glucose: endocrine or genotoxic prevalence? Horm Metab Res 38:650–655CrossRefPubMed

Title: Infusion fluids contain harmful glucose degradation products
Authors: Anna Bryland
Marcus Broman
Martin Erixon
Bengt Klarin
Torbjörn Lindén
Hans Friberg
Anders Wieslander
Per Kjellstrand
Claudio Ronco
Ola Carlsson
Gabriela Godaly
Publication date: 01-07-2010
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 7/2010
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-010-1873-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Infusion fluids contain harmful glucose degradation products

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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