International Urology and Nephrology

, Volume 51, Issue 6, pp 1035–1042 | Cite as

Pentosidine in chronic hemodialysis patients: relation with arteriovenous fistula morphology and function

  • Maria TicalaEmail author
  • Dacian Călin Tirinescu
  • Crina Claudia Rusu
  • Diana Moldovan
  • Alina Ramona Potra
  • Anca Laura Coman
  • Cosmina Ioana Bondor
  • Livia Budisan
  • Ina Maria Kacsó
Nephrology - Original Paper



It has been suggested that advanced glycation end products (AGEs) are involved in atherogenesis, vascular calcification and remodeling, including neointimal hyperplasia, in renal and non-renal patients. Their relevance for arteriovenous fistula (AVF) function has been poorly studied to date, with only one clinical study addressing the issue of thrombosis of vascular access in relation to AGEs in dialysis patients. We aimed to evaluate the relationship between serum pentosidine and AVF morphology and function.


Eighty-eighth hemodialysis patients with patent native AVF were included. Ultrasound examination of AVF evaluated blood flow in the brachial artery, resistivity index (RI), the diameter of the vessels and the presence of stenosis. AVF and cardiovascular history were recorded, routine clinical and laboratory evaluation was performed and serum pentosidine was assessed.


Forty-eight patients (54.54%) had AVF stenosis. Pentosidine correlated in univariate analysis with cholesterol (r = 0.270, p = 0.01), triglycerides (r = 0.309, p = 0.003), calcium (r = 0.040, p < 0.001) and inversely to dialysis vintage (r = − 0.453, p < 0.001), access vintage (r = − 0.432, p = 0.001), phosphate (r = − 0.211, p = 0.04), parathyroid hormone (r = − 0.211, p = 0.04), urea (r = − 0.230, p = 0.03), residual diameter of AVF (r = − 0.023, p = 0.03). In multivariate regression calcium (p = 0.006), access vintage (p = 0.03), and residual diameter of AVF vein (p = 0.02) remain significantly linked to pentosidine. Patients with pentosidine above median had higher cholesterol (179.91 vs. 160.97, p = 0.04), triglycerides (187.18 vs. 129.31, p = 0.002) and higher prevalence of hypertension (93.70% vs. 84.10%, p = 0.02).


Our study suggests that pentosidine could be associated to vascular access morphology and function in dialysis patients.


Arteriovenous fistula Hemodialysis Advanced glycation end product Stenosis Pentosidine 


Compliance with ethical standards

Conflict of interest

Maria Ticala declares that she has no conflict of interest. Dacian Tirinescu declares that he has no conflict of interest. Crina Claudia Rusu declares that she has no conflict of interest. Diana Moldovan declares that she has no conflict of interest. Alina Ramona Potra declares that she has no conflict of interest. Anca Laura Coman declares that she has no conflict of interest. Cosmina Ioana Bondor declares that she has no conflict of interest. Livia Budisan declares that she has no conflict of interest. Ina Maria Kacso declares that she has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Qibin Z, Jennifer MA, Richard DS, John WB, Thomas OM (2009) A perspective on the maillard reaction and the analysis of protein glycation by mass spectrometry: probing the pathogenesis of chronic disease. J Proteome Res 8:754–769CrossRefGoogle Scholar
  2. 2.
    Cho SJ, Roman G, Yeboah F, Konishi Y (2007) The road to advanced glycation end products: a mechanistic perspective. Curr Med Chem 14:1653–1671CrossRefPubMedGoogle Scholar
  3. 3.
    Vistoli G, De Maddis D, Cipak A, Zarkovic N, Carini M, Aldini G (2013) Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation. Free Radic Res 47:3–27CrossRefPubMedGoogle Scholar
  4. 4.
    Kooman JP, Kotanko P, Schols AM, Shiels PG, Stenvinkel P (2014) Chronic kidney disease and premature ageing. Nat Rev Nephrol 10:732–742CrossRefPubMedGoogle Scholar
  5. 5.
    Semba RD, Ferrucci L, Fink JC, Sun K, Beck J, Dalal M, Guralnik JM, Fried LP (2009) Advanced glycation end products and their circulating receptors and level of kidney function in older community-dwelling women. Am J Kidney Dis 53:51–58CrossRefPubMedGoogle Scholar
  6. 6.
    Busch M, Franke S, Muller A, Wolf M, Gerth J, Ott U, Niwa T, Stein G (2004) Potential cardiovascular risk factors in chronic kidney disease: aGEs, total homocysteine and metabolites, and the C-reactive protein. Kidney Int 66:338–647CrossRefPubMedGoogle Scholar
  7. 7.
    Vaziri ND (2004) Oxidative stress in uremia: nature, mechanisms, and potential consequences. Semin Nephrol 24:469–473CrossRefPubMedGoogle Scholar
  8. 8.
    Miyata T, Ypersele Van, de Strihou C, Kurokawa K, Baynes JW (1999) Alterations in nonenzymatic biochemistry in uremia: origin and significance of “carbonyl stress” in long-term uremic complications. Kidney Int 55:389–399CrossRefPubMedGoogle Scholar
  9. 9.
    Meerwaldt R, Graaff R, Oomen PHN, Links TP, Jager JJ, Alderson NL, Thorpe SR, Baynes JW, Gans ROB, Smit AJ (2004) Simple non-invasive assessment of advanced glycation end product accumulation. Diabetologia 47:1324–1330CrossRefPubMedGoogle Scholar
  10. 10.
    Busch M, Franke S, Ruster C, Gunter W (2010) Advanced glycation end-products and the kidney. Eur J Clin Invest 40:742–755CrossRefPubMedGoogle Scholar
  11. 11.
    Stinghen AE, Massy ZA, Vlassara H, Striker GE, Boullier A (2016) Uremic toxicity of advanced glycation end products in CKD. J Am Soc Nephrol 27:354–370CrossRefPubMedGoogle Scholar
  12. 12.
    Schwing WD, Erhard P, Holloman CK, Weigel KA, Blankschaen SC, Anderson JM, Siegel CT, Seaman DS, Valente JF, DeOreo PB (2004) Thrombotic events and markers of oxidation and inflammation in hemodialysis. Hemodial Int 8:338–343CrossRefPubMedGoogle Scholar
  13. 13.
    Uhlin F, Fridolin I, Magnusson M, Linberg L-G (2006) Dialysis dose (K t/V) and clearance variation sensitivity using measurement of ultraviolet absorbance (on-line), blood urea, dialysate urea and ionic dialysance. Nephrol Dial Transpl 21:2225–2231CrossRefGoogle Scholar
  14. 14.
    Napoli M, Russo F, Pati C (2011) AVF Monitoring. In: Napoli M (ed) echo color doppler & vascular accesses for hemodialysis, 1st edn. Wichtig, Milano, pp 46–62Google Scholar
  15. 15.
    National Kidney Foundation (2006) KDOQI Clinical practice guidelines for vascular access. Am J Kidney Dis. CrossRefGoogle Scholar
  16. 16.
    Tordoir J, Cannaud B, Haage P et al (2007) EBPG on vascular access. Nephrol Dial Transpl 22:88–117CrossRefGoogle Scholar
  17. 17.
    Schmidli J, Widmer M, Basile C et al (2018) Vascular access: clinical practice guidelines of the European Society for vascular surgery. Eur J Vasc Endovasc Surg 55:757–818CrossRefPubMedGoogle Scholar
  18. 18.
    Clark TW, Hirsch DA, Jindal KJ, Veugelers PJ, Leblanc J (2002) Outcome and prognostic factors of restenosis after percutaneos treatment of native hemodialysis fistulas. J Vasc Interv Radiol 13:51–59CrossRefPubMedGoogle Scholar
  19. 19.
    Miyata T, Ueda Y, Yasuda Y, Izuhara Y, Wada T, Jadoul M, Saito A, Kurokawa K, Ypersele Van, de Strihou C (1998) Accumulation of carbonyls accelerates the formation of pentosidine, an advanced glycation end product: carbonyl stress in uremia. J Am Soc Nephrol 9:2349–2356PubMedGoogle Scholar
  20. 20.
    Raj DS, Choudhury D, Welbourne TC, Levi M (2000) Advanced glycation end products: a Nephrologist’s perspective. Am J Kidney Dis 35:365–380CrossRefPubMedGoogle Scholar
  21. 21.
    Suliman ME, Heimburger O, Barany P, Anderstam B, Pecoits-Filho R, Ayala RE, Qureshi AR, Ekholm FI, Lindholm B, Stenvinkel P (2003) Plasma pentosidine is associated with inflammation and malnutrition in end-stage renal disease patients starting on dialysis therapy. J Am Soc Nephrol 14:1614–1622CrossRefPubMedGoogle Scholar
  22. 22.
    Stein G, Franke S, Mahiout A, Schneider S, Sperschneider H, Borst S, Vienken J (2001) Influence of dialysis modalities on serum AGE levels in end-stage renal disease patients. Nephrol Dial Transplant 16:999–1008CrossRefPubMedGoogle Scholar
  23. 23.
    Jadoul M, Ueda Y, Yasuda Y, Saito A, Robert A, Ishida N, Kurokawa K, de Strihou CV, Miyata T (1999) Influence of hemodialysis membrane type on pentosidine plasma level, a marker of “carbonyl stress”. Kidney Int 55:2487–2492CrossRefPubMedGoogle Scholar
  24. 24.
    Nishizawa Y, Koyama H, Inaba M (2012) AGEs and cardiovascular diseases in patients with end-stage renal diseases. J Ren Nutr 22:128–133CrossRefPubMedGoogle Scholar
  25. 25.
    Ueno H, Koyama H, Fukumoto S, Tanaka S, Shoji T, Shoji T, Emoto M, Tahara H, Inaba M, Kakiya R, Tabata T, Miyata T, Nishizawa Y (2011) Advanced glycation end products, carotid atherosclerosis, and circulating endothelial progenitor cells in patients with end-stage renal disease. Metabolism 60:453–459CrossRefPubMedGoogle Scholar
  26. 26.
    Suliman ME, Stenvinkel P, Jogestrand T, Maruyama Y, Qureshi AR, Bárány P, Heimbürger O, Lindholm B (2006) Plasma pentosidine and total homocysteine levels in relation to change in common carotid intima-media area in the first year of dialysis therapy. Clin Nephrol 66:418–425CrossRefPubMedGoogle Scholar
  27. 27.
    McNair E, Qureshi M, Prasad K, Pearce C (2016) Atherosclerosis and the Hypercholesterolemic AGE–RAGE Axis. Int J Angiol 25:110–116CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Machowska A, Carrero JJ, Lindholm B, Stenvinkel P (2016) Therapeutics targeting persistent inflammation in chronic kidney disease. Transl Res 167:204–213CrossRefPubMedGoogle Scholar
  29. 29.
    Yung-Ho H, Yu-Chun Y, Yi-Chun L, Li-Chin S (2018) Antiplatelet agents maintain arteriovenous fistula and graft function in patients receiving hemodialysis: a nationwide case–control study. PLOS One. CrossRefGoogle Scholar
  30. 30.
    Sakaguchi T, Yan SF, Yan SD, Belov D, Rong LL, Sousa M, Andrassy M, Marso SP, Duda S, Arnold B, Liliensiek B, Nawroth PP, Stern DM, Schmidt AM, Naka Y (2003) Central role of RAGE-dependent neointimal expansion in arterial restenosis. J Clin Invest 111:959–972CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Roy-Chaudhury P, Sukhatme VP, Cheung AK (2006) Hemodialysis vascular access dysfunction: a cellular and molecular viewpoint. J Am Soc Nephrol 17:1112–1127CrossRefPubMedGoogle Scholar
  32. 32.
    Weiss MF, Scivittaro V, Anderson JM (2001) Oxidative stress and increased expression of growth factors in the lesions of failed hemodialysis access. Am J Kidney Dis 37:970–980CrossRefPubMedGoogle Scholar
  33. 33.
    Du H, Li P, Wang J, Qing X, Li W (2012) The interaction of amyloid β and the receptor for advanced glycation end products induces matrixmetalloproteinase-2 expression in brain endothelial cells. Cell Mol Neurobiol 32:141–147CrossRefPubMedGoogle Scholar
  34. 34.
    Tirinescu DC, Tomuleasa C, Pop L, Bondor CI, Vlăduţiu DŞ, Paţiu IM, Rusu CC, Moldovan DT, Potra A, Kacsó IM (2017) Matrix-metalloproteinase-2 predicts arteriovenous fistula failure in hemodialysis patients. Ther Apher Dial 21:586–591CrossRefPubMedGoogle Scholar
  35. 35.
    Smith GE, Gohil R, Chetter IC (2012) Factors affecting the patency of arteriovenous fistulas for dialysis access. J Vasc Surg 55:849–855CrossRefPubMedGoogle Scholar
  36. 36.
    Zhou Z, Immel D, Xia Xi C, Bierhaus A, Lin Mei XF, Nawroth P, Stern DM, Xiong WC (2006) Regulation of osteoclast function and bone mass by RAGE. J Exp Med 203:1067–1080CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Sanguineti R, Storace D, Monacelli F, Federici A, Odett P (2008) Pentosidine effects on human osteoblasts in vitro ann. N Y Acad Sci 1126:166–172CrossRefGoogle Scholar
  38. 38.
    Kakuta T, Tanaka R, Hyodo T, Suzuki H, Kanai G, Nagaoka M, Takahashi H, Hirawa M, Oogushi Y, Miyata T, Kobayashi H, Fukagawa M, Saito A (2011) Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients. Am J Kidney Dis 57:422–431CrossRefPubMedGoogle Scholar
  39. 39.
    Yamamoto T, Ozono K, Miyauchi A, Kasayama S, Kojima Y, Shima M, Okada S (2001) Role of advanced glycation end products in adynamic bone disease in patients with diabetic nephropathy. Am J Kidney Dis 38:161–164CrossRefGoogle Scholar
  40. 40.
    Panuccio V, Mallamaci F, Tripepi G, Parlongo S, Cutrupi P, Asahi K, Miyata T, Zoccali C (2002) Low parathyroid hormone and pentosidine in hemodialysis patients. Am J Kidney Dis 40:810–815CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Maria Ticala
    • 1
    Email author
  • Dacian Călin Tirinescu
    • 1
  • Crina Claudia Rusu
    • 1
  • Diana Moldovan
    • 1
  • Alina Ramona Potra
    • 1
  • Anca Laura Coman
    • 1
  • Cosmina Ioana Bondor
    • 2
  • Livia Budisan
    • 3
  • Ina Maria Kacsó
    • 1
  1. 1.Department of Nephrology“Iuliu Haţieganu” University of Medicine and PharmacyCluj-NapocaRomania
  2. 2.Department of Informatics and Biostatistics“Iuliu Haţieganu” University of Medicine and PharmacyCluj-NapocaRomania
  3. 3.Research Center for Functional Genomic, Biomedicine and Translational Medicine“Iuliu Haţieganu” University of Medicine and PharmacyCluj-NapocaRomania

Personalised recommendations