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Value and level of circulating endothelial progenitor cells, angiogenesis factors and mononuclear cell apoptosis in patients with chronic kidney disease

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Abstract

Background

Chronic renal failure on dialysis can reduce the number of circulating endothelial progenitor cells (EPCs), but this biomarker has not been fully investigated in patients with chronic kidney disease (CKD). A link between CKD and increased mononuclear cell apoptosis (MCA) in circulation has been reported but the effect of vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF)-1α, two angiogenesis factors, on circulating EPC levels in CKD has not been clarified. This study examined the relationships between the numbers of circulating EPCs and the severity of CKD, degree of MCA and serum levels of VEGF and SDF-1α in CKD patients.

Methods

The numbers of circulating EPCs (CD31/CD34+, CD62E/CD34+, KDR/CD34+, CXCR4/CD34+) were measured in 166 patients with varying degrees of CKD under regular treatment at an outpatient department and in 30 volunteer control subjects.

Results

CKD patients had significantly lower numbers of EPCs (p < 0.007), higher MCA in circulation and higher serum levels of VEGF and SDF-1 compared with the control subjects (all p < 0.001). Compared with patients with early CKD (stages I–III), patients with late CKD [stage IV–V or end-stage renal disease (ESRD)] had significantly lower numbers of EPCs (CXCR4/CD34+), higher MCA, and elevated serum levels of VEGF and SDF-1α (all p < 0.01). Serum VEGF level but not MCA or SDF-1α was strongly correlated with increased numbers of circulating EPCs. Multivariate analysis showed that ESRD along with lower serum albumin was independently predictive of lower numbers of circulating EPCs (p < 0.04).

Conclusion

Circulating EPCs were markedly reduced in CKD patients. ESRD was strongly and independently predictive of decreased numbers of circulating EPCs.

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References

  1. Ronco C, McCullough P, Anker SD, Anand I, Aspromonte N, Bagshaw SM, et al. Cardio-renal syndromes: report from the consensus conference of the acute dialysis quality initiative. Eur Heart J. 2010;31:703–11.

    Article  PubMed  Google Scholar 

  2. Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. 2008;52:1527–39.

    Article  PubMed  Google Scholar 

  3. Seyfarth M, Kastrati A, Mann JF, Ndrepepa G, Byrne RA, Schulz S, et al. Prognostic value of kidney function in patients with ST-elevation and non–ST-elevation acute myocardial infarction treated with percutaneous coronary intervention. Am J Kidney Dis. 2009;54:830–9.

    Article  PubMed  Google Scholar 

  4. Herzog CA, Ma JZ, Collins AJ. Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med. 1998;339:799–805.

    Article  PubMed  CAS  Google Scholar 

  5. Chertow GM, Normand SL, Silva LR, McNeil BJ. Survival after acute myocardial infarction in patients with end-stage renal disease: results from the cooperative cardiovascular project. Am J Kidney Dis. 2000;35:1044–51.

    Article  PubMed  CAS  Google Scholar 

  6. Culleton BF, Larson MG, Wilson PW, Evans JC, Parfrey PS, Levy D. Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency. Kidney Int. 1999;56:2214–9.

    Article  PubMed  CAS  Google Scholar 

  7. Shlipak MG, Massie BM. The clinical challenge of cardiorenal syndrome. Circulation. 2004;110:1514–7.

    Article  PubMed  Google Scholar 

  8. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000;87:840–4.

    Article  PubMed  CAS  Google Scholar 

  9. Cross J. Endothelial dysfunction in uremia. Blood Purif. 2002;20:459–61.

    Article  PubMed  CAS  Google Scholar 

  10. Kawashima S. Malfunction of vascular control in lifestyle-related diseases: endothelial nitric oxide (NO) synthase/NO system in atherosclerosis. J Pharmacol Sci. 2004;96:411–9.

    Article  PubMed  CAS  Google Scholar 

  11. Faure V, Dou L, Sabatier F, Cerini C, Sampol J, Berland Y, et al. Elevation of circulating endothelial microparticles in patients with chronic renal failure. J Thromb Haemost. 2006;4:566–73.

    Article  PubMed  CAS  Google Scholar 

  12. Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007;116:85–97.

    Article  PubMed  Google Scholar 

  13. Stam F, van Guldener C, Becker A, Dekker JM, Heine RJ, Bouter LM, et al. Endothelial dysfunction contributes to renal function-associated cardiovascular mortality in a population with mild renal insufficiency: the Hoorn study. J Am Soc Nephrol. 2006;17:537–45.

    Article  PubMed  CAS  Google Scholar 

  14. Annuk M, Lind L, Linde T, Fellstrom B. Impaired endothelium dependent vasodilatation in renal failure in humans. Nephrol Dial Transplant. 2001;16:302–6.

    Article  PubMed  CAS  Google Scholar 

  15. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–7.

    Article  PubMed  CAS  Google Scholar 

  16. Hill JM, Zalos G, Halcox JP. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593–600.

    Article  PubMed  Google Scholar 

  17. Lambiase PD, Edwards RJ, Anthopoulos P, Rahman S, Meng YG, Bucknall CA, et al. Circulating humoral factors and endothelial progenitor cells in patients with differing coronary collateral support. Circulation. 2004;109:2986–92.

    Article  PubMed  Google Scholar 

  18. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005;353:999–1007.

    Article  PubMed  CAS  Google Scholar 

  19. Chironi G, Walch L, Pernollet MG, Gariepy J, Levenson J, Rendu F, et al. Decreased number of circulating CD34+KDR+ cells in asymptomatic subjects with preclinical atherosclerosis. Atherosclerosis. 2007;191:115–20.

    Article  PubMed  CAS  Google Scholar 

  20. Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001;89:E1–7.

    Article  PubMed  CAS  Google Scholar 

  21. Bahlmann FH, DeGroot K, Duckert T, Niemczyk E, Bahlmann E, Boehm SM, et al. Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin. Kidney Int. 2003;64:1648–52.

    Article  PubMed  CAS  Google Scholar 

  22. Jourde-Chiche N, Dou L, Sabatier F, Calaf R, Cerini C, Robert S, et al. Levels of circulating endothelial progenitor cells are related to uremic toxins and vascular injury in hemodialysis patients. J Thromb Haemost. 2009;7:1576–84.

    Article  PubMed  CAS  Google Scholar 

  23. Jie KE, Zaikova MA, Bergevoet MW, Westerweel PE, Rastmanesh M, Blankestijn PJ, et al. Endothelial progenitor cells in patients on extracorporeal maintenance dialysis therapy. Nephrol Dial Transplant. 2010;25:1875–82.

    Article  PubMed  CAS  Google Scholar 

  24. Wang CH, Verma S, Hsieh IC, Chen YJ, Kuo LT, Yang NI, et al. Enalapril increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system. J Mol Cell Cardiol. 2006;41:34–43.

    Article  PubMed  CAS  Google Scholar 

  25. Imanishi T, Tsujioka H, Akasaka T. Endothelial progenitor cells dysfunction and senescence: contribution to oxidative stress. Curr Cardiol Rev. 2008;4:275–86.

    Article  PubMed  CAS  Google Scholar 

  26. Shastry S, Ingram AJ, Scholey JW, James LR. Homocysteine induces mesangial cell apoptosis via activation of p38-mitogen-activated protein kinase. Kidney Int. 2007;71:304–11.

    Article  PubMed  CAS  Google Scholar 

  27. Verzola D, Villaggio B, Procopio V, Gandolfo MT, Gianiorio F, Famà A, et al. Androgen-mediated apoptosis of kidney tubule cells: role of c-Jun amino terminal kinase. Biochem Biophys Res Commun. 2009;387:531–6.

    Article  PubMed  CAS  Google Scholar 

  28. Sardenberg C, Suassuna P, Andreoli MC, Watanabe R, Dalboni MA, Manfredi SR, et al. Effects of uraemia and dialysis modality on polymorphonuclear cell apoptosis and function. Nephrol Dial Transplant. 2006;21:160–5.

    Article  PubMed  Google Scholar 

  29. Tsai TH, Lin YC, Sun CK, Chung SY, Chai HT, Yang CH, et al. Prognostic value of circulating dead monocytes in patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Cardiology. 2010;117:131–9.

    Article  PubMed  Google Scholar 

  30. Desouza CV, Hamel FG, Bidasee K, O’Connell K. Role of inflammation and insulin resistance in endothelial progenitor cell dysfunction. Diabetes. 2011;60:1286–94.

    Article  PubMed  CAS  Google Scholar 

  31. Chen J, Jin J, Song M, Dong H, Zhao G, Huang L. C-reactive protein down-regulates endothelial nitric oxide synthase expression and promotes apoptosis in endothelial progenitor cells through receptor for advanced glycation end-products. Gene. 2012;496:128–35.

    Article  PubMed  CAS  Google Scholar 

  32. Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139:137–47.

    PubMed  Google Scholar 

  33. Yip HK, Chang LT, Chang WN, Lu CH, Liou CW, Lan MY, et al. Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke. Stroke. 2008;39:69–74.

    Article  PubMed  Google Scholar 

  34. Chen CH, Cheng BC, Leu S, Sun CK, Chua S, Yen CH, et al. Circulating level of endothelial progenitor cells in healthy Taiwanese. Acta Cardiol Sin. 2010;26:94–101.

    Google Scholar 

  35. Hong F, Tuyama A, Lee TF, Loke J, Agarwal R, Cheng X, et al. Hepatic stellate cells express functional CXCR4: role in stromal cell-derived factor-1α-mediated stellate cell activation. Hepatology. 2009;49:2055–67.

    Article  PubMed  CAS  Google Scholar 

  36. Zeller M, Korandji C, Guilland JC, Sicard P, Vergely C, Lorgis L, et al. Impact of asymmetric dimethylarginine on mortality after acute myocardial infarction. Arterioscler Thromb Vascular Biol. 2008;28:954–60.

    Article  CAS  Google Scholar 

  37. Herzog CA, Littrell K, Arko C, Frederick PD, Blaney M. Clinical characteristics of dialysis patients with acute myocardial infarction in the United States: a collaborative project of the United States Renal Data System and the National Registry of Myocardial Infarction. Circulation. 2007;116:1465–72.

    Article  PubMed  Google Scholar 

  38. Chonchol M, Whittle J, Desbien A, Orner MB, Petersen LA, Kressin NR. Chronic kidney disease is associated with angiographic coronary artery disease. Am J Nephrol. 2008;28:354–60.

    Article  PubMed  Google Scholar 

  39. Bonello L, De Labriolle A, Roy P, Steinberg DH, Okabe T, Pinto Slottow TL, et al. Impact of optimal medical therapy and revascularization on outcome of patients with chronic kidney disease and on dialysis who presented with acute coronary syndrome. Am J Cardiol. 2008;102:535–40.

    Article  PubMed  Google Scholar 

  40. Navaneethan SD, Pansini F, Perkovic V, Manno C, Pellegrini F, Johnson DW, et al. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2009;2:CD007784.

    Google Scholar 

  41. Fellstrom BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360:1395–407.

    Article  PubMed  CAS  Google Scholar 

  42. Liu Y, Coresh J, Eustace JA, Longenecker JC, Jaar B, Fink NE, et al. Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. JAMA. 2004;291:451–9.

    Article  PubMed  CAS  Google Scholar 

  43. Leavey SF, Strawderman RL, Jones CA, Port FK, Held PJ. Simple nutritional indicators as independent predictors of mortality in hemodialysis patients. Am J Kidney Dis. 1998;31:997–1006.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Hon-Kan Yip.

Additional information

B.-C. Cheng and Y.-T. Chen contributed equally to this work.

Y.-L. Chen and H.-K. Yip contributed equally to this work.

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Chen, YT., Cheng, BC., Ko, SF. et al. Value and level of circulating endothelial progenitor cells, angiogenesis factors and mononuclear cell apoptosis in patients with chronic kidney disease. Clin Exp Nephrol 17, 83–91 (2013). https://doi.org/10.1007/s10157-012-0664-9

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  • DOI: https://doi.org/10.1007/s10157-012-0664-9

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