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Effects of bone and mineral metabolism on arterial elasticity in chronic renal failure

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Abstract

Arterial stiffness (Ast) individually predicts cardiovascular (CV) mortality. Ast increases via vascular calcification and can be characterized by pulse wave velocity (PWV). We assessed the influence of mineral and bone metabolism on Ast in dialyzed (D) and renal transplanted (Tx) children by measuring fetuin-A and bone markers [bone-specific alkaline phosphatase (BALP); beta-CrossLaps (β)]. Normalized PWV/height (PWV/h) of 11 D and 17 Tx patients was measured by applanation tonometry. Levels of calcium (Ca), phosphate (P), fetuin-A, and bone markers were analyzed. Ca × P/fetuin-A ratio was calculated to characterize the balance of calcification and inhibition. Cumulative dose of calcitriol was also assessed. Fetuin-A was lower in D and Tx compared with healthy controls. Bone markers and Ca × P/fetuin-A of D were significantly higher than those of Tx and controls. In D PWV/h correlated with Ca × P/fetuin-A and BALP (r = 0.8; p = 0.005, r = 0.6, p = 0.05, respectively); BALP correlated with Ca × P/fetuin-A (r = 0.7, p = 0.01). In Tx, there was a correlation between calcitriol administered before transplantation and PWV/h (r = 0.5, p = 0.04). Increased bone turnover was coupled with an increased potential of calcium-phosphate precipitation, as shown by the increased Ca × P/fetuin-A. It might explain the connection between disturbed mineral and bone metabolism and Ast. Tx might be beneficial on Ast, though follow-up studies are needed.

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References

  1. Pannier B, Guerin AP, Marchais SJ, Safar ME, London GM (2005) Stiffness of capacitive and conduit arteries: prognostic significance for end-stage renal disease patients. Hypertension 45:592–596

    CAS  PubMed  Google Scholar 

  2. Blacher J, Safar ME, Guerin AP, Pannier B, Marchais SJ, London GM (2003) Aortic pulse wave velocity index and mortality in end-stage renal disease. Kidney Int 63:1852–1860

    PubMed  Google Scholar 

  3. London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H (2003) Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 18:1731–1740

    PubMed  Google Scholar 

  4. Cozzolino M, Mazzaferro S, Pugliese F, Brancaccio D (2008) Vascular calcification and uremia: what do we know? Am J Nephrol 28:339–346

    PubMed  Google Scholar 

  5. Mazzaferro S, Pasquali M, Pugliese F, Barresi G, Carbone I, Francone M, Sardella D, Taggi F (2007) Serum levels of calcification inhibition proteins and coronary artery calcium score: comparison between transplantation and dialysis. Am J Nephrol 27:75–83

    CAS  PubMed  Google Scholar 

  6. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H (2006) Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 27:2588–2605

    Google Scholar 

  7. Guerin AP, Pannier B, Metivier F, Marchais SJ, London GM (2008) Assessment and significance of arterial stiffness in patients with chronic kidney disease. Curr Opin Nephrol Hypertens 17:635–641

    PubMed  Google Scholar 

  8. Laurent S, Boutouyrie P (2007) Arterial stiffness: a new surrogate end point for cardiovascular disease? J Nephrol 20(Suppl 12):S45–S50

    PubMed  Google Scholar 

  9. Frimodt-Moller M, Nielsen AH, Kamper AL, Strandgaard S (2008) Reproducibility of pulse-wave analysis and pulse-wave velocity determination in chronic kidney disease. Nephrol Dial Transplant 23:594–600

    PubMed  Google Scholar 

  10. Guerin AP, Pannier B, Marchais SJ, London GM (2006) Cardiovascular disease in the dialysis population: prognostic significance of arterial disorders. Curr Opin Nephrol Hypertens 15:105–110

    PubMed  Google Scholar 

  11. Laurent S, Boutouyrie P (2005) Arterial stiffness and stroke in hypertension: therapeutic implications for stroke prevention. CNS Drugs 19:1–11

    PubMed  Google Scholar 

  12. London GM, Marchais SJ, Guerin AP (2004) Arterial stiffness and function in end-stage renal disease. Adv Chronic Kidney Dis 11:202–209

    PubMed  Google Scholar 

  13. Kis E, Cseprekal O, Horvath Z, Katona G, Fekete BC, Hrapka E, Szabo A, Szabo AJ, Fekete A, Reusz GS (2008) Pulse wave velocity in end-stage renal disease: influence of age and body dimensions. Pediatr Res 63:95–98

    PubMed  Google Scholar 

  14. Cseprekal O, Kis E, Schaffer P, Othmane Tel H, Fekete BC, Vannay A, Szabo AJ, Remport A, Szabo A, Tulassay T, Reusz GS (2009) Pulse wave velocity in children following renal transplantation. Nephrol Dial Transplant 24:309–315

    PubMed  Google Scholar 

  15. Briese S, Claus M, Querfeld U (2008) Arterial stiffness in children after renal transplantation. Pediatr Nephrol 23:2241–2245

    PubMed  Google Scholar 

  16. Gavrilovici C, Brumariu O, Dimitriu AG, Covic A, Boiculese L, Russu R (2006) Arterial stiffness in pediatric hypertension. Rev Med Chir Soc Med Nat Iasi 110:259–266

    PubMed  Google Scholar 

  17. Covic A, Mardare N, Gusbeth-Tatomir P, Brumaru O, Gavrilovici C, Munteanu M, Prisada O, Goldsmith DJ (2006) Increased arterial stiffness in children on haemodialysis. Nephrol Dial Transplant 21:729–735

    PubMed  Google Scholar 

  18. Shroff RC, Donald AE, Hiorns MP, Watson A, Feather S, Milford D, Ellins EA, Storry C, Ridout D, Deanfield J, Rees L (2007) Mineral metabolism and vascular damage in children on dialysis. J Am Soc Nephrol 18:2996–3003

    CAS  PubMed  Google Scholar 

  19. Ketteler M, Westenfeld R, Schlieper G, Brandenburg V (2005) Pathogenesis of vascular calcification in dialysis patients. Clin Exp Nephrol 9:265–270

    PubMed  Google Scholar 

  20. Ketteler M, Westenfeld R, Schlieper G, Brandenburg V, Floege J (2005) “Missing” inhibitors of calcification: general aspects and implications in renal failure. Pediatr Nephrol 20:383–388

    PubMed  Google Scholar 

  21. Price PA, Lim JE (2003) The inhibition of calcium phosphate precipitation by fetuin is accompanied by the formation of a fetuin-mineral complex. J Biol Chem 278:22144–22152

    CAS  PubMed  Google Scholar 

  22. Price PA, Nguyen TM, Williamson MK (2003) Biochemical characterization of the serum fetuin-mineral complex. J Biol Chem 278:22153–22160

    CAS  PubMed  Google Scholar 

  23. Ketteler M, Giachelli C (2006) Novel insights into vascular calcification. Kidney Int Suppl:S5–9

    Google Scholar 

  24. Moe SM, Chen NX (2008) Mechanisms of vascular calcification in chronic kidney disease. J Am Soc Nephrol 19:213–216

    CAS  PubMed  Google Scholar 

  25. Moe SM, O’Neill KD, Duan D, Ahmed S, Chen NX, Leapman SB, Fineberg N, Kopecky K (2002) Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. Kidney Int 61:638–647

    PubMed  Google Scholar 

  26. Borchhardt K, Sulzbacher I, Benesch T, Fodinger M, Sunder-Plassmann G, Haas M (2007) Low-turnover bone disease in hypercalcemic hyperparathyroidism after kidney transplantation. Am J Transplant 7:2515–2521

    CAS  PubMed  Google Scholar 

  27. Waller S, Ridout D, Rees L (2007) Effect of haemodialysis on markers of bone turnover in children. Pediatr Nephrol 22:586–592

    PubMed  Google Scholar 

  28. Moe SM (2006) Vascular calcification: hardening of the evidence. Kidney Int 70:1535–1537

    CAS  PubMed  Google Scholar 

  29. Reusz GS, Szabo AJ, Peter F, Kenesei E, Sallay P, Latta K, Szabo A, Szabo A, Tulassay T (2000) Bone metabolism and mineral density following renal transplantation. Arch Dis Child 83:146–151

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 69:1945–1953

    CAS  PubMed  Google Scholar 

  31. Soergel M, Kirschstein M, Busch C, Danne T, Gellermann J, Holl R, Krull F, Reichert H, Reusz GS, Rascher W (1997) Oscillometric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial including 1141 subjects. J Pediatr 130:178–184

    CAS  PubMed  Google Scholar 

  32. Salvi P, Lio G, Labat C, Ricci E, Pannier B, Benetos A (2004) Validation of a new non-invasive portable tonometer for determining arterial pressure wave and pulse wave velocity: the PulsePen device. J Hypertens 22:2285–2293

    CAS  PubMed  Google Scholar 

  33. Schwartz GJ, Furth SL (2007) Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatr Nephrol 22:1839–1848

    PubMed  Google Scholar 

  34. Jono S, Shioi A, Ikari Y, Nishizawa Y (2006) Vascular calcification in chronic kidney disease. J Bone Miner Metab 24:176–181

    PubMed  Google Scholar 

  35. Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2005) Cardiac and vascular adaptation in pediatric patients with chronic kidney disease: role of calcium-phosphorus metabolism. J Am Soc Nephrol 16:2796–2803

    CAS  PubMed  Google Scholar 

  36. Mitsnefes MM (2008) Cardiovascular complications of pediatric chronic kidney disease. Pediatr Nephrol 23:27–39

    PubMed  PubMed Central  Google Scholar 

  37. Laurent S (2006) Surrogate measures of arterial stiffness: do they have additive predictive value or are they only surrogates of a surrogate? Hypertension 47:325–326

    CAS  PubMed  Google Scholar 

  38. Laurent S (2008) Aortic, carotid and femoral stiffness: how do they relate? Towards reference values. J Hypertens 26:1305–1306

    CAS  PubMed  Google Scholar 

  39. Khoshdel AR, Thakkinstian A, Carney SL, Attia J (2006) Estimation of an age-specific reference interval for pulse wave velocity: a meta-analysis. J Hypertens 24:1231–1237

    CAS  PubMed  Google Scholar 

  40. Mitsnefes MM (2005) Cardiovascular disease in children with chronic kidney disease. Adv Chronic Kidney Dis 12:397–405

    Google Scholar 

  41. Shroff R, Ledermann S (2009) Long-term outcome of chronic dialysis in children. Pediatr Nephrol 24:463–474

    PubMed  PubMed Central  Google Scholar 

  42. Marchais SJ, Guerin AP, Pannier BM, Levy BI, Safar ME, London GM (1993) Wave reflections and cardiac hypertrophy in chronic uremia. Influence of body size. Hypertension 22:876–883

    CAS  PubMed  Google Scholar 

  43. London GM, Guerin AP, Verbeke FH, Pannier B, Boutouyrie P, Marchais SJ, Metivier F (2007) Mineral metabolism and arterial functions in end-stage renal disease: potential role of 25-hydroxyvitamin D deficiency. J Am Soc Nephrol 18:613–620

    CAS  PubMed  Google Scholar 

  44. Toussaint ND, Kerr PG (2007) Vascular calcification and arterial stiffness in chronic kidney disease: implications and management. Nephrology (Carlton) 12:500–509

    Google Scholar 

  45. Shroff RC, Shah V, Hiorns MP, Schoppet M, Hofbauer LC, Hawa G, Schurgers LJ, Singhal A, Merryweather I, Brogan P, Shanahan C, Deanfield J, Rees L (2008) The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis. Nephrol Dial Transplant 23:3263–3271

    CAS  PubMed  Google Scholar 

  46. Heiss A, Eckert T, Aretz A, Richtering W, van Dorp W, Schafer C, Jahnen-Dechent W (2008) Hierarchical role of fetuin-A and acidic serum proteins in the formation and stabilization of calcium phosphate particles. J Biol Chem 283:14815–14825

    CAS  PubMed  Google Scholar 

  47. Heiss A, DuChesne A, Denecke B, Grotzinger J, Yamamoto K, Renne T, Jahnen-Dechent W (2003) Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. J Biol Chem 278:13333–13341

    CAS  PubMed  Google Scholar 

  48. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB (2000) Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342:1478–1483

    CAS  PubMed  Google Scholar 

  49. Ketteler M, Brandenburg V, Jahnen-Dechent W, Westenfeld R, Floege J (2005) Do not be misguided by guidelines: the calcium x phosphate product can be a Trojan horse. Nephrol Dial Transplant 20:673–677

    PubMed  Google Scholar 

  50. Berner YN, Shike M (1988) Consequences of phosphate imbalance. Annu Rev Nutr 8:121–148

    CAS  PubMed  Google Scholar 

  51. Brown WE, Eidelman N, Tomazic B (1987) Octacalcium phosphate as a precursor in biomineral formation. Adv Dent Res 1:306–313

    CAS  PubMed  Google Scholar 

  52. Szabo A, Sallay P, Tausz I (1990) The serum hormone levels, phosphate complex concentrations and enzyme activities in haemodialysed and kidney-transplanted children. Acta Paediatr Hung 30:73–88

    CAS  PubMed  Google Scholar 

  53. Sarkozi L, Szabo A, Ors E, Beck MT (1984) Calculated distribution of various inorganic phosphate constituents in body fluids, based on the principles of complex equilibria. Clin Physiol Biochem 2:221–226

    CAS  PubMed  Google Scholar 

  54. Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Bohm R, Metzger T, Wanner C, Jahnen-Dechent W, Floege J (2003) Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Lancet 361:827–833

    CAS  PubMed  Google Scholar 

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Acknowledgement

This study was supported by OTKA-071730, NNF 78846, ETT 435/2006 and TÁMOP-4.2.2.-08/1/KMR-2008-2004. AJS is recipient of Bolyai Scholarship.

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Authors and Affiliations

  1. First Department of Pediatrics, Semmelweis University, Budapest, Bókay János u. 53–54, 1083, Hungary

    Éva Kis, Orsolya Cseprekál, Kata Kelen, Dóra Ferenczi, Andrea Kerti, Attila J. Szabó, Antal Szabó & György S. Reusz

  2. Central Laboratory, Semmelweis University, Budapest, Hungary

    Edina Bíró

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  1. Éva Kis
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  2. Orsolya Cseprekál
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Correspondence to György S. Reusz.

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Éva Kis and Orsolya Cseprekál contributed equally to the manuscript.

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Kis, É., Cseprekál, O., Bíró, E. et al. Effects of bone and mineral metabolism on arterial elasticity in chronic renal failure. Pediatr Nephrol 24, 2413–2420 (2009). https://doi.org/10.1007/s00467-009-1292-9

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