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Dialyse aktuell 2014; 18(9): 474-482
DOI: 10.1055/s-0034-1396563
Dialyse
© Georg Thieme Verlag Stuttgart · New York

Optimierung des kardiovaskulären Risikos bei Dialysepatienten – Phosphat und Vitamin D

Optimizing cardiovascular risk in dialysis patients – Phosphate and vitamin D
Markus van der Giet
1   Charité Centrum 13 – Schwerpunkt Nephrologie Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin (Klinikdirektor: Prof. Dr. Walter Zidek)
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Publication Date:
24 November 2014 (online)

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Die kardiovaskuläre Morbidität und Mortalität bei Patienten mit Dialysepflichtigkeit ist extrem hoch. Es kommt bei Niereninsuffizienz zu einer deutlichen Störung im Kalzium-Phosphat-Haushalt. Hierdurch entsteht auch eine stark progrediente vaskuläre Kalzifizierung, die die kardiovaskuläre Mortalität relevant beeinflusst. In den letzten Jahren gab es viele Bemühungen, den Phosphat- und Kalziumhaushalt durch die Gabe von unterschiedlichen Phosphatbindern, aber auch durch Gabe von Präparaten mit aktivem Vitamin D zu beeinflussen. Hier zeigt sich, dass sowohl Phosphatbinder wie auch die Gabe von Vitamin D in der Lage sind, die vaskuläre Kalzifizierung zu beeinflussen, wobei in klinischen Studien der Effekt dann sehr moderat bis kaum messbar war. In der vorliegenden Arbeit soll eine Übersicht über aktuell verwendete Phosphatbinder bzw. auch Vitamin-D-Derivate sowie über ihre Auswirkungen auf die potenziellen kardiovaskulären Effekte bei Patienten mit terminaler Niereninsuffizienz gegeben werden.

The cardiovascular morbidity and mortality in patients on chronic renal replacement therapy is extremely high. Chronic renal insufficiency induces substantial disturbances in the calcium phosphate homeostasis. An excessive strong progredient vascular calcification is observed which has deep impact on the patients' cardiovascular mortality. In the last years, many attempts were undertaken to reduce calcium and phosphate disturbances using phosphate resorption inhibitors or active vitamin D supplementation. Both phosphate resorption inhibitors and active vitamin D substances at low concentrations show an impact on vascular calcification. The effect shown in clinical studies, however, is very moderate and sometimes even not detectable. In the present work, a review is given on the cardiovascular risk reducing effects of phosphate binders and vitamin D supplementation in patients with end-stage renal disease.

Key words

cardiovascular risk - dialysis patients - phosphate - vitamin D
 

  • Literatur

  • 1 Goodman WG, Goldin J, Kuizon BD et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342: 1478-1783
    CrossrefGoogle Scholar
  • 2 London GM, Guérin AP, Marchais SJ et al. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003; 18: 1731-1740
    CrossrefGoogle Scholar
  • 3 Shimada T, Hasegawa H, Yamazaki Y et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 2004; 19: 429-435
    Google Scholar
  • 4 Chartsrisak K, Vipattawat K, Assanatham M et al. Mineral metabolism and outcomes in chronic kidney disease stage 2-4 patients. BMC Nephrol 2013; 14: 14-14
    CrossrefGoogle Scholar
  • 5 Faul C, Amaral AP, Oskouei B et al. FGF23 induces left ventricular hypertrophy. J Clin Invest 2011; 121: 4393-4408
    CrossrefGoogle Scholar
  • 6 Scialla JJ, Xie H, Rahman M et al. Chronic Renal Insufficiency Cohort (CRIC) Study Investigators. Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol 2014; 25: 349-360
    CrossrefGoogle Scholar
  • 7 Isakova T, Xie H, Yang W et al. Chronic Renal Insufficiency Cohort (CRIC) Study Group. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 2011; 305: 2432-2439
    CrossrefGoogle Scholar
  • 8 Moe SM, O'Neill KD, Duan D et al. Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. Kidney Int 2002; 61: 638-647
    CrossrefGoogle Scholar
  • 9 Neven E, D'Haese PC. Vascular calcification in chronic renal failure: what have we learned from animal studies?. Circ Res 2011; 108: 249-264
    CrossrefGoogle Scholar
  • 10 Cardus A, Panizo S, Parisi E et al. Differential effects of vitamin D analogs on vascular calcification. J Bone Miner Res 2007; 22: 860-866
    CrossrefGoogle Scholar
  • 11 Yang H, Curinga G, Giachelli CM. Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro. Kidney Int 2004; 66: 2293-2299
    CrossrefGoogle Scholar
  • 12 Lim K, Lu TS, Molostvov G et al. Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation 2012; 125: 2243-2255
    CrossrefGoogle Scholar
  • 13 Oschatz E, Benesch T, Kodras K et al. Changes of coronary calcification after kidney transplantation. Am J Kidney Dis 2006; 48: 307-313
    CrossrefGoogle Scholar
  • 14 Mazzaferro S, Pasquali M, Taggi F et al. Progression of coronary artery calcification in renal transplantation and the role of secondary hyperparathyroidism and inflammation. Clin J Am Soc Nephrol 2009; 4: 685-690
    CrossrefGoogle Scholar
  • 15 Seyahi N, Cebi D, Altiparmak MR et al. Progression of coronary artery calcification in renal transplant recipients. Nephrol Dial Transplant 2012; 27: 2101-2107
    CrossrefGoogle Scholar
  • 16 Daugirdas JT, Finn WF, Emmett M et al. The phosphate binder equivalent dose. Semin Dial 2011; 24: 41-49
    CrossrefGoogle Scholar
  • 17 Che Y, Bing C, Akhtar J et al. Lanthanum carbonate prevents accelerated medial calcification in uremic rats: role of osteoclast-like activity. J Transl Med 2013; 11: 308-308
    CrossrefGoogle Scholar
  • 18 Wada K, Wada Y. Evaluation of aortic calcification with lanthanum carbonate vs. calcium-based phosphate binders in maintenance hemodialysis patients with type 2 diabetes mellitus: an open-label randomized controlled trial. Ther Apher Dial 2014; 18: 353-360
    CrossrefGoogle Scholar
  • 19 Wilson R, Zhang P, Smyth M, Pratt R. Assessment of survival in a 2-year comparative study of lanthanum carbonate versus standard therapy. Curr Med Res Opin 2009; 25: 3021-3028
    CrossrefGoogle Scholar
  • 20 Maier JA. Low magnesium and atherosclerosis: an evidence-based link. Mol Aspects Med 2003; 24: 137-146
    CrossrefGoogle Scholar
  • 21 Montezano AC, Zimmerman D, Yusuf H et al. Vascular smooth muscle cell differentiation to an osteogenic phenotype involves TRPM7 modulation by magnesium. Hypertension 2010; 56: 453-462
    CrossrefPubMedGoogle Scholar
  • 22 De Schutter TM, Behets GJ, Geryl H et al. Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia. Kidney Int 2013; 83: 1109-1117
    CrossrefGoogle Scholar
  • 23 de Francisco AL, Leidig M, Covic AC et al. Evaluation of calcium acetate/magnesium carbonate as a phosphate binder compared with sevelamer hydrochloride in haemodialysis patients: a controlled randomized study (CALMAG study) assessing efficacy and tolerability. Nephrol Dial Transplant 2010; 25: 3707-3717
    CrossrefGoogle Scholar
  • 24 Covic A, Passlick-Deetjen J, Kroczak M et al. A comparison of calcium acetate/magnesium carbonate and sevelamer-hydrochloride effects on fibroblast growth factor-23 and bone markers: post hoc evaluation from a controlled, randomized study. Nephrol Dial Transplant 2013; 28: 2383-2392
    CrossrefGoogle Scholar
  • 25 Wuthrich RP, Chonchol M, Covic A et al. Randomized clinical trial of the iron-based phosphate binder PA21 in hemodialysis patients. Clin J Am Soc Nephrol 2013; 8: 280-289
    CrossrefGoogle Scholar
  • 26 Yokoyama K, Hirakata H, Akiba T et al. Effect of oral JTT-751 (ferric citrate) on hyperphosphatemia in hemodialysis patients: results of a randomized, double-blind, placebo-controlled trial. Am J Nephrol 2012; 36: 478-487
    CrossrefGoogle Scholar
  • 27 Phan O, Maillard M, Peregaux C et al. PA21, a new iron-based noncalcium phosphate binder, prevents vascular calcification in chronic renal failure rats. J Pharmacol Exp Ther 2013; 346: 281-289
    CrossrefGoogle Scholar
  • 28 Guida B, Cataldi M, Riccio E et al. Plasma p-cresol lowering effect of sevelamer in peritoneal dialysis patients: evidence from a Cross-Sectional Observational Study. PLoS One 2013; 8
    Google Scholar
  • 29 Vlassara H, Uribarri J, Cai W et al. Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease. Clin J Am Soc Nephrol 2012; 7: 934-942
    CrossrefGoogle Scholar
  • 30 Di Iorio B, Molony D, Bell C et al. INDEPENDENT Study Investigators. Sevelamer versus calcium carbonate in incident hemodialysis patients: results of an open-label 24-month randomized clinical trial. Am J Kidney Dis 2013; 62: 771-778
    CrossrefGoogle Scholar
  • 31 Block GA, Wheeler DC, Persky MS et al. Effects of phosphate binders in moderate CKD. J Am Soc Nephrol 2012; 23: 1407-1415
    CrossrefGoogle Scholar
  • 32 Locatelli F, Spasovski G, Dimkovic N et al. The effects of colestilan versus placebo and sevelamer in patients with CKD 5D and hyperphosphataemia: a 1-year prospective randomized study. Nephrol Dial Transplant 2014; 29: 1061-1073
    CrossrefGoogle Scholar
  • 33 Mizobuchi M, Finch JL, Martin DR, Slatopolsky E. Differential effects of vitamin D receptor activators on vascular calcification in uremic rats. Kidney Int 2007; 72: 709-715
    CrossrefGoogle Scholar
  • 34 Mathew S, Lund RJ, Chaudhary LR et al. Vitamin D receptor activators can protect against vascular calcification. J Am Soc Nephrol 2008; 19: 1509-1519
    CrossrefGoogle Scholar
  • 35 Lomashvili KA, Wang X, O'Neill WC. Role of local versus systemic vitamin D receptors in vascular calcification. Arterioscler Thromb Vasc Biol 2014; 34: 146-151
    CrossrefGoogle Scholar
  • 36 Park CW, Oh YS, Shin YS et al. Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism. Am J Kidney Dis 1999; 33: 73-81
    CrossrefGoogle Scholar
  • 37 Thadhani R, Appelbaum E, Pritchett Y et al. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA 2012; 307: 674-684
    CrossrefGoogle Scholar
  • 38 Duranton F, Rodriguez-Ortiz ME, Duny Y et al. Vitamin D treatment and mortality in chronic kidney disease: a systematic review and meta-analysis. Am J Nephrol 2013; 37: 239-248
    CrossrefGoogle Scholar
  • 39 Di Iorio B, Bellasi A, Russo D. INDEPENDENT Study Investigators. Mortality in kidney disease patients treated with phosphate binders: a randomized study. Clin J Am Soc Nephrol 2012; 7: 487-493
    CrossrefGoogle Scholar