American Journal of Nephrology

Original Report: Laboratory Investigation

Osteoprotegerin Is the Strongest Predictor for Progression of Arterial Calcification in Peritoneal Dialysis Patients

Avila M.a · Mora C.a · Prado M.C.a · Zavala M.b · Paniagua R.a · Mexican Collaborative Group

Author affiliations

aUnidad de Investigación Médica en Enfermedades Nefrológicas, and bDepartamento de Radiología e Imagen, Hospital de Especialidades, CMN SXXI, Instituto Mexicano del Seguro Social, Mexico, Mexico

Keywords: Vascular calcificationOsteoprotegerinPeritoneal dialysisDiabetes mellitusArterial calcification

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Am J Nephrol 2017;46:39-46
https://doi.org/10.1159/000477380

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Article / Publication Details

First-Page Preview
Abstract of Original Report: Laboratory Investigation

Received: November 13, 2016
Accepted: March 27, 2017
Published online: June 15, 2017
Issue release date: July 2017

Number of Print Pages: 8
Number of Figures: 1
Number of Tables: 3

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: https://www.karger.com/AJN

Abstract

Background: Arterial calcification (AC) is frequent in patients with end stage renal disease and is also considered a risk factor for later morbidity and mortality. However, long-term factors associated with the process are not well known. We analyzed the trends over time of biomarkers related with development and progression of AC in incident patients on peritoneal dialysis (PD). Methods: We performed a prospective study with 186 patients on PD followed up for 1 year. We analyzed the progression of AC in the abdominal aorta and pelvic vessels by calcification score (CaSc), using16-cut computerized multidetector tomography at baseline and 1 year. Variables related with PD treatment, inflammation, and mineral metabolism were measured at baseline, 6, and 12 months of follow-up. Changes in biochemical variables were analyzed for their relationship with changes in AC. Results: Over 1 year, the number of patients with AC increased from 47 to 56%, and CaSc from 355 (interquartile range [IQR] 75-792) to 529 (IQR 185-1632). A total of 43.5% of patients remained free of calcification, 11.7% had new calcifications, and 44.8% had progression of calcification. Older age, diabetes, high systolic blood pressure, body mass index, cholesterol, and osteoprotegerin (OPG), as well as lower levels of albumin, serum creatinine, and osteocalcin, were associated with development of new, and rapid progression of, calcification. In multivariate logistic analysis, OPG remained the most significant (OR 1.27, 95% CI 1.11-1.47, p < 0.001). Conclusion: OPG was the strongest risk factor associated with new development and rapid progression of AC in incident PD patients.

© 2017 S. Karger AG, Basel

References

  1. Merjanian R, Budoff M, Adler S, Berman N, Mehrotra R: Coronary artery, aortic wall, and valvular calcification in nondialyzed individuals with type 2 diabetes and renal disease. Kidney Int 2003;64:263-271.
    External Resources
  2. Roman-Garcia P, Carrillo-Lopez N, Cannata-Andia JB: Pathogenesis of bone and mineral related disorders in chronic kidney disease: key role of hyperphosphatemia. J Ren Care 2009;35(suppl 1):34-38.
    External Resources
  3. Shigematsu T, Kono T, Satoh K, Yokoyama K, Yoshida T, Hosoya T, Shirai K: Phosphate overload accelerates vascular calcium deposition in end-stage renal disease patients. Nephrol Dial Transplant 2003;18(suppl 3):iii86-iii89.
    External Resources
  4. Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ, Proudfoot D, Jahnen-Dechent W, Weissberg PL, Shanahan CM: Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. J Am Soc Nephrol 2004;15:2857-2867.
    External Resources
  5. Malluche HH, Blomquist G, Monier-Faugere MC, Cantor TL, Davenport DL: High parathyroid hormone level and osteoporosis predict progression of coronary artery calcification in patients on dialysis. J Am Soc Nephrol 2015;26:2534-2544.
    External Resources
  6. Henaut L, Sanchez-Nino MD, Aldamiz-Echevarria Castillo G, Sanz AB, Ortiz A: Targeting local vascular and systemic consequences of inflammation on vascular and cardiac valve calcification. Expert Opin Ther Targets 2016;20:89-105.
    External Resources
  7. Stompor T, Krasniak A, Sulowicz W, Dembinska-Kiec A, Janda K, Wojcik K, Tabor B, Kowalczyk-Michalek ME, Zdzienicka A, Janusz-Grzybowska E: Changes in common carotid artery intima-media thickness over 1 year in patients on peritoneal dialysis. Nephrol Dial Transplant 2005;20:404-412.
    External Resources
  8. Yamada S, Oshima M, Watanabe Y, Miyake H: Arterial location-specific calcification at the carotid artery and aortic arch for chronic kidney disease, diabetes mellitus, hypertension, and dyslipidemia. Calcif Tissue Int 2014;95:267-274.
    External Resources
  9. Russo D, Morrone LF, Imbriaco M, Pota A, Russo L, Scognamiglio B, Sorrentino R: Coronary artery calcification and outcomes in diabetic patients with and without chronic kidney disease. Blood Purif 2013;36:17-20.
    External Resources
  10. Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM: Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 2001;38:938-942.
    External Resources
  11. London GM: Role of arterial wall properties in the pathogenesis of systolic hypertension. Am J Hypertens 2005;18(1 pt 2):19S-22S.
    External Resources
  12. Raggi P, Bellasi A, Ferramosca E, Islam T, Muntner P, Block GA: Association of pulse wave velocity with vascular and valvular calcification in hemodialysis patients. Kidney Int 2007;71:802-807.
    External Resources
  13. Schousboe JT, Taylor BC, Kiel DP, Ensrud KE, Wilson KE, McCloskey EV: Abdominal aortic calcification detected on lateral spine images from a bone densitometer predicts incident myocardial infarction or stroke in older women. J Bone Miner Res 2008;23:409-416.
    External Resources
  14. Walsh CR, Cupples LA, Levy D, Kiel DP, Hannan M, Wilson PW, O'Donnell CJ: Abdominal aortic calcific deposits are associated with increased risk for congestive heart failure: the Framingham Heart Study. Am Heart J 2002;144:733-739.
    External Resources
  15. Okuno S, Ishimura E, Kitatani K, Fujino Y, Kohno K, Maeno Y, Maekawa K, Yamakawa T, Imanishi Y, Inaba M, Nishizawa Y: Presence of abdominal aortic calcification is significantly associated with all-cause and cardiovascular mortality in maintenance hemodialysis patients. Am J Kidney Dis 2007;49:417-425
    External Resources
  16. Sigrist MK, Taal MW, Bungay P, McIntyre CW: Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease. Clin J Am Soc Nephrol 2007;2:1241-1248.
    External Resources
  17. Bover J, Urena-Torres P, Gorriz JL, Lloret MJ, da Silva I, Ruiz-Garcia C, Chang P, Rodriguez M, Ballarin J: Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications. Nefrologia 2016;36:597-608.
    External Resources
  18. Bellasi A, Raggi P: Vascular calcification in chronic kidney disease: usefulness of a marker of vascular damage. J Nephrol 2011;24(suppl 18):S11-S15.
    External Resources
  19. Liabeuf S, Okazaki H, Desjardins L, Fliser D, Goldsmith D, Covic A, Wiecek A, Ortiz A, Martinez-Castelao A, Lindholm B, Suleymanlar G, Mallamaci F, Zoccali C, London G, Massy ZA: Vascular calcification in chronic kidney disease: are biomarkers useful for probing the pathobiology and the health risks of this process in the clinical scenario? Nephrol Dial Transplant 2014;29:1275-1284.
    External Resources
  20. Kim SM, Lee J, Ryu OH, Lee KW, Kim HY, Seo JA, Kim SG, Kim NH, Baik SH, Choi DS, Choi KM: Serum osteoprotegerin levels are associated with inflammation and pulse wave velocity. Clin Endocrinol 2005;63:594-598.
    External Resources
  21. Onyia JE, Miles RR, Yang X, Halladay DL, Hale J, Glasebrook A, McClure D, Seno G, Churgay L, Chandrasekhar S, Martin TJ: In vivo demonstration that human parathyroid hormone 1-38 inhibits the expression of osteoprotegerin in bone with the kinetics of an immediate early gene. J Bone Miner Res 2000;15:863-871.
    External Resources
  22. Morena M, Jaussent I, Dupuy AM, Bargnoux AS, Kuster N, Chenine L, Leray-Moragues H, Klouche K, Vernhet H, Canaud B, Cristol JP: Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis: potential partners in vascular calcifications. Nephrol Dial Transplant 2015;30:1345-1356.
    External Resources
  23. Mikami S, Hamano T, Fujii N, Nagasawa Y, Isaka Y, Moriyama T, Matsuhisa M, Ito T, Imai E, Hori M: Serum osteoprotegerin as a screening tool for coronary artery calcification score in diabetic pre-dialysis patients. Hypertens Res 2008;31:1163-1170.
    External Resources
  24. Nitta K, Akiba T, Uchida K, Kawashima A, Yumura W, Kabaya T, Nihei H: The progression of vascular calcification and serum osteoprotegerin levels in patients on long-term hemodialysis. Am J Kidney Dis 2003;42:303-309.
    External Resources
  25. Fabbian F, Catalano C, Orlandi V, Conte MM, Lupo A, Catizone L: Evaluation of aortic arch calcification in hemodialysis patients. J Nephrol 2005;18:289-293.
    External Resources
  26. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R: Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990;15:827-832.
    External Resources
  27. Keshaviah PR, Nolph KD, Moore HL, Prowant B, Emerson PF, Meyer M, Twardowski ZJ, Khanna R, Ponferrada L, Collins A: Lean body mass estimation by creatinine kinetics. J Am Soc Nephrol 1994;4:1475-1485.
    External Resources
  28. Temmar M, Liabeuf S, Renard C, Czernichow S, Esper NE, Shahapuni I, Presne C, Makdassi R, Andrejak M, Tribouilloy C, Galan P, Safar ME, Choukroun G, Massy Z: Pulse wave velocity and vascular calcification at different stages of chronic kidney disease. J Hypertens 2010;28:163-169.
    External Resources
  29. Taniwaki H, Ishimura E, Tabata T, Tsujimoto Y, Shioi A, Shoji T, Inaba M, Inoue T, Nishizawa Y: Aortic calcification in haemodialysis patients with diabetes mellitus. Nephrol Dial Transplant 2005;20:2472-2478.
    External Resources
  30. Porter CJ, Stavroulopoulos A, Roe SD, Pointon K, Cassidy MJ: Detection of coronary and peripheral artery calcification in patients with chronic kidney disease stages 3 and 4, with and without diabetes. Nephrol Dial Transplant 2007;22:3208-3213.
    External Resources
  31. Shroff RC, McNair R, Figg N, Skepper JN, Schurgers L, Gupta A, Hiorns M, Donald AE, Deanfield J, Rees L, Shanahan CM: Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis. Circulation 2008;118:1748-1757.
    External Resources
  32. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS: Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998;12:1260-1268.
    External Resources
  33. Van Campenhout A, Golledge J: Osteoprotegerin, vascular calcification and atherosclerosis. Atherosclerosis 2009;204:321-329.
    External Resources
  34. Ketteler M, Wuthrich RP, Floege J: Management of hyperphosphataemia in chronic kidney disease-challenges and solutions. Clin Kidney J 2013;6:128-136.
    External Resources
  35. Jean G, Bresson E, Terrat JC, Vanel T, Hurot JM, Lorriaux C, Mayor B, Chazot C: Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant 2009;24:948-955.
    External Resources
  36. Paniagua R, Ventura MD, Avila-Diaz M, Hinojosa-Heredia H, Mendez-Duran A, Cisneros A, Gomez AM, Cueto-Manzano A, Trinidad P, Obrador GT, Garcia-Lopez E, Lindholm B: Reaching targets for mineral metabolism clinical practice guidelines and its impact on outcomes among Mexican chronic dialysis patients. Arch Med Res 2013;44:229-234.
    External Resources
  37. Merle E, Roth H, London GM, Jean G, Hannedouche T, Bouchet JL, Drüeke T, Fouque D, Daugas E; French Calcium and Phosphate Observatory: Low parathyroid hormone status induced by high dialysate calcium is an independent risk factor for cardiovascular death in hemodialysis patients. Kidney Int 2016;89:666-674
    External Resources
  38. Schoppet M, Shroff RC, Hofbauer LC, Shanahan CM: Exploring the biology of vascular calcification in chronic kidney disease: what's circulating? Kidney Int 2008;73:384-390.
    External Resources
  39. Sage AP, Tintut Y, Demer LL: Regulatory mechanisms in vascular calcification. Nat Rev Cardiol 2010;7:528-536.
    External Resources
  40. Ozkok A, Caliskan Y, Sakaci T, Erten G, Karahan G, Ozel A, Unsal A, Yildiz A: Osteoprotegerin/RANKL axis and progression of coronary artery calcification in hemodialysis patients. Clin J Am Soc Nephrol 2012;7:965-973.
    External Resources
  41. Stolina M, Schett G, Dwyer D, Vonderfecht S, Middleton S, Duryea D, Pacheco E, Van G, Bolon B, Feige U, Zack D, Kostenuik P: RANKL inhibition by osteoprotegerin prevents bone loss without affecting local or systemic inflammation parameters in two rat arthritis models: comparison with anti-TNFalpha or anti-IL-1 therapies. Arthritis Res Ther 2009;11:R187.
    External Resources
  42. Kurz K, Herold M, Russe E, Klotz W, Weiss G, Fuchs D: Effects of antitumor necrosis factor therapy on osteoprotegerin, neopterin, and sRANKL concentrations in patients with rheumatoid arthritis. Dis Markers 2015;2015:276969.
    External Resources
  43. Matsubara K, Stenvinkel P, Qureshi AR, Carrero JJ, Axelsson J, Heimburger O, Barany P, Alvestrand A, Lindholm B, Suliman ME: Inflammation modifies the association of osteoprotegerin with mortality in chronic kidney disease. J Nephrol 2009;22:774-782.
    External Resources
  44. Avila-Diaz M, Ventura MD, Valle D, Vicente-Martinez M, Garcia-Gonzalez Z, Cisneros A, Furlong MD, Gomez AM, Prado-Uribe MD, Amato D, Paniagua R: Inflammation and extracellular volume expansion are related to sodium and water removal in patients on peritoneal dialysis. Perit Dial Int 2006;26:574-580.
    External Resources
  45. Kim YL, Biesen WV: Fluid overload in peritoneal dialysis patients. Semin Nephrol 2017;37:43-53.
    External Resources
  46. Zoccali C, Bolignano D, D'Arrigo G, Dekker FW, Fliser D, Heine GH, Jager KJ, Kanbay M, Mallamaci F, Massy Z, Ortiz A, Parati G, Rossignol P, Tripepi G, Vanholder R, Wiecek A, London G; European Renal and Cardiovascular Medicine (EURECA-m) Working Group of the European Renal Association-European Dialysis Transplantation Association (ERA-EDTA): Validity of vascular calcification as a screening tool and as a surrogate end point in clinical research. Hypertension 2015;66:3-9.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Report: Laboratory Investigation

Received: November 13, 2016
Accepted: March 27, 2017
Published online: June 15, 2017
Issue release date: July 2017

Number of Print Pages: 8
Number of Figures: 1
Number of Tables: 3

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: https://www.karger.com/AJN

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