Störungen des Mineral- und Knochenhaushalts bei Niereninsuffizienz und Gefäßverkalkungen

Zusammenfassung

Im Rahmen einer neuen Betrachtungsweise der renalen Osteopathie soll nun der Terminus der “Störungen des Mineral- und Knochenhaushalts bei Niereninsuffizienz” (engl. Akronym: CKD-MBD) die ehemals rein knochenzentrische Sicht zu diesem Krankheitsbild ablösen. CKD-MBD wird nun betrachtet als ein Syndrom, zu dessen Diagnose auch der Nachweis kardiovaskulärer Verkalkungen gehört. Es ist bereits gut untersucht, dass die Prävalenz von Gefäßverkalkungen mit fortschreitender Niereninsuffizienz zunimmt und diese bei Weitem schwerwiegender sind als in einer nierengesunden Normalbevölkerung. Es wurde außerdem erkannt, dass spezifische pathophysiologische Störungen den Verlauf von Weichteilverkalkungen determinieren, wie beispielsweise die Hyperphosphatämie, die osteogene Differenzierung von Gefäßwandzellen und Verkalkungsinhibitormangel. Der Schweregrad kardiovaskulärer Verkalkungen entspricht zudem einem erheblichen Risikofaktor für kardiovaskuläre Ereignisse. Es bestehen jedoch noch Unsicherheiten hinsichtlich der Sensitivitäten und Spezifitäten der verfügbaren bildgebenden und funktionellen Nachweisverfahren. Ebenfalls ist noch nicht bewiesen, dass eine Progressionshemmung von Gefäßverkalkungen in der Niereninsuffizienz unmittelbaren Einfluss auf patientenrelevante Endpunkte hat. Schließlich bedarf es noch der Definition von geradlinigen klinischen Algorithmen zur Diagnostik und Therapie, nachdem kardiovaskuläre Verkalkungen bei niereninsuffizienten Patienten detektiert wurden.

Summary

Recently, a new view was taken on renal osteopathy, and it was suggested to replace this term by Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) leaving its historically “osteocentric” character behind. CKD-MBD should now be regarded as a syndrome which also includes the detection of arterial, valvular, and myocardial calcifications. It is generally well-recognized that with progressively decreasing kidney function the prevalence of vascular calcification increases when compared to the general population. It is also recognized that there are distinct pathophysiological disturbances involved such as hyperphosphatemia, osteogenic differentiation of the vessel wall and deficiencies of calcification inhibitors. Cardiovascular calcification is a potent risk factor in CKD patients associated with adverse clinical outcomes including cardiovascular events and death. However, there are uncertainties about the sensitivity and specificity of available imaging and functional detection tests. Further, there is uncertainty, whether altering the progression of calcification will directly impact on patient outcome in CKD patients. Finally,a definition is lacking for clinically useful algorithms on how to proceed with diagnostic and therapeutic strategies followinga positive calcification test result.

Schlüsselwörter

Gefäßverkalkungen - Hyperphosphatämie - Verkalkungsinhibitoren - CKD-MBD

Keywords

Vascular calcification - hyperphosphatemia - calcification inhibitors - CKD-MBD

• Literatur

• 1 ACCF/AHA 2007. Clinical Expert Consensus Document on Coronary Artery Calcium Scoring by Computed Tomography in Global Cardiovascular Risk Assessment and in Evaluation of Patients With Chest Pain. Circulation. 2007 115. 402-426.
• 2 Adragao T, Pires A, Lucas C. et al. A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients. Nephrol Dial Transplant 2004; 19: 1480-1488.
• 3 Baigent C, Landray MJ, Wheeler DC. Misleading associations between cholesterol and vascular outcomes in dialysis patients: the need for randomized trials. Seminars in Dialysis 2007; 20: 498-503.
• 4 Bellasi A, Ferramosca E, Muntner P. et al. Correlation of simple imaging tests and coronary artery calcium measured by computed tomography in hemodialysis patients. Kidney Int 2006; 70: 1623-1628.
• 5 Blacher J, Guerin AP, Pannier B. et al. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 2001; 38: 938-942.
• 6 Block GA, Spiegel DM, Ehrlich J. et al. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 2005; 68: 1815-1824.
• 7 Block GA, Raggi P, Bellasi A. et al. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int 2007; 71: 438-441.
• 8 Bursztyn M, Motro M, Grossman E, Shemesh J. Accelerated coronary artery calcification in mildly reduced renal function of high-risk hypertensives: a 3-year prospective observation. J Hypertension 2003; 21: 1953-1959.
• 9 Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002; 62: 245-255.
• 10 Giachelli CM. Vascular calcification mechanisms. J Am Soc Nephrol 2004; 15: 2959-2964.
• 11 Gross ML, Meyer HP, Ziebart H. et al. Calcification of coronary intima and media: immunohistochemistry, backscatter imaging, and x-ray analysis in renal and nonrenal patients. Clin J Am Soc Nephrol 2007; 02: 121-134.
• 12 Haffner D, Hocher B, Müller D. et al. Systemic cardiovascular disease in uremic rats induced by 1,25(OH)2D3. J Hypertens 2005; 23: 1067-1075.
• 13 Haydar AA, Hujairi NM, Covic AA. et al. Coronary artery calcification is related to coronary atherosclerosis in chronic renal disease patients: a study comparing EBCT-generated coronary artery calcium scores and coronary angiography. Kidney Int 2004; 65: 1790-1794.
• 14 Hernández D, Rufino M, Bartolomei S. et al. Clinical impact of preexisting vascular calcifications on mortality after renal transplantation. Kidney Int 2005; 67: 2015-2020.
• 15 Ibels LS, Stewart JH, Mahony JF, Sheil AG. Deaths from occlusive arterial disease in renal allograft recipients. Br Med J 1974; 03: 552-554.
• 16 Ix JH, Shlipak MG, Katz R. et al. Kidney function and aortic valve and mitral annular calcification in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Kidney Dis 2007; 50: 412-420.
• 17 Ketteler M, Schlieper G, Floege J. Calcification and cardiovascular health: new insights into an old phenomenon. Hypertension 2006; 47: 1027-1034.
• 18 Ketteler M, Biggar P, Brandenburg VM. et al. Calciphylaxie: Neues zur Epidemiologie, Pathophysiologie und Therapiemöglichkeiten. Dtsch Arztebl 2007; 104: A3481-A3485.
• 19 Kronenberg F, Mündle M, Längle M, Neyer U. Prevalence and progression of peripheral arterial calcifications in patients with ESRD. Am J Kidney Dis 2003; 41: 140-148.
• 20 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.
• 21 Lopez I, Aguilera-Tejero E, Mendoza FJ. et al. Calcimimetic R-568 decreases extraosseous calcifications in uremic rats treated with calcitriol. J Am Soc Nephrol 2006; 17: 795-804.
• 22 Lopez I, Mendoza FJ, Aguilera-Tejero E. et al. The effect of calcitriol, paricalcitol, and a calcimimetic on extraosseous calcifications in uremic rats. Kidney Int 2008; 73: 300-307.
• 23 Matsuoka M, Iseki K, Tamashiro M. et al. Impact of high coronary artery calcification score (CACS) on survival in patients on chronic hemodialysis. Clin Exp Nephrol 2004; 08: 54-58.
• 24 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.
• 25 Moe SM, Duan D, Doehle BP. et al. Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels. Kidney Int 2003; 63: 1003-1011.
• 26 Moe SM, O’Neill KD, Reslerova M. et al. Natural history of vascular calcification in dialysis and transplant patients. Nephrol Dial Transplant 2004; 19: 2387-2393.
• 27 Nitta K, Akiba T, Suzuki K. et al. Assessment of coronary artery calcification in hemodialysis patients using multi-detector spiral CT scan. Hypertension Res 2004; 27: 527-533.
• 28 Oei HH, Vliegenthart R, Deckers JW. et al. The association of Rose questionnaire angina pectoris and coronary calcification in a general population: the Rotterdam Coronary Calcification Study. Ann Epidemiol 2004; 14: 431-436.
• 29 Okuno S, Ishimura E, Kitatani K. et al. 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.
• 30 Panuccio V, Tripepi R, Tripepi G. et al. Heart valve calcifications, survival, and cardiovascular risk in hemodialysis patients. Am J Kidney Dis 2004; 43: 479-484.
• 31 Qunibi W, Moustafa M, Muenz LR. et al. A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation-2 (CARE-2) study. Am J Kidney Dis 2008; 51: 952-965.
• 32 Raggi P, Bommer J, Chertow GM. Valvular calcification in hemodialysis patients randomized to calcium- based phosphorus binders or sevelamer. J Heart Valve Dis 2004; 13: 134-141.
• 33 Raggi P, Bellasi A, Ferramosca E. et al. Association of pulse wave velocity with vascular and valvular calcification in hemodialysis patients. Kidney Int 2007; 71: 802-807.
• 34 Russo D, Corrao S, Miranda I. et al. Progression of coronary artery calcification in predialysis patients. Am J Nephrology 2007; 27: 152-158.
• 35 Russo D, Miranda I, Ruocco C. et al. The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney Int 2007; 72: 1255-1261.
• 36 Schwarz U, Buzello M, Ritz E. et al. Morphology of coronary atherosclerotic lesions in patients with end- stage renal failure. Nephrol Dial Transplant 2000; 15: 218-223.
• 37 Sharma R, Pellerin D, Gaze DC. et al. Mitral annular calcification predicts mortality and coronary artery disease in end stage renal disease. Atherosclerosis 2007; 191: 348-354.
• 38 Shroff RC, Donald AE, Hiorns MP. et al. Mineral metabolism and vascular damage in children on dialysis. JAm Soc Nephrol 2007; 18: 2996-3003.
• 39 Sigrist M, Bungay P, Taal MW, McIntyre CW. Vascular calcification and cardiovascular function in chronic kidney disease. Nephrol Dial Transplant 2006; 21: 707-714.
• 40 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; 02: 1241-1248.
• 41 Stompór T, Rajzer M, Pasowicz M. et al. Coronary artery calcification, common carotid artery intima-media thickness and aortic pulse wave velocity in patients on peritoneal dialysis. Int J Artif Organs 2006; 29: 736-744.
• 42 Suki WN, Zabaneh R, Cangiano JL. et al. Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Kidney Int 2007; 72 (09) 1130-1137.
• 43 Tatler GL, Baillod RA, Varghese Z. et al. Evolution of bone disease over 10 years in 135 patients with terminal renal failure. Br Med J 1973; 04: 315-319.
• 44 Varma R, Aronow WS, McClung JA. et al. Prevalence of valve calcium and association of valve calcium with coronary artery disease, atherosclerotic vascular disease, and all-cause mortality in 137 patients undergoing hemodialysis for chronic renal failure. Am J Cardiol 2005; 95: 742-743.
• 45 Vliegenthart R, Hollander M, Breteler MM. et al. Stroke is associated with coronary calcification as detected by electron-beam CT: the Rotterdam Coronary Calcification Study. Stroke 2002; 33: 462-465.
• 46 Vliegenthart R, Oudkerk M, Song B. et al. Coronary calcification detected by electron-beam computed tomography and myocardial infarction. The Rotterdam Coronary Calcification Study. Eur Heart J 2002; 23: 1596-1603.
• 47 Wang AY, Wang M, Woo J. et al. Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in longterm peritoneal dialysis patients: a prospective study. J Am Soc Nephrol 2003; 14: 159-168.
• 48 Wanner C, Krane V, März W. et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005; 353: 238-248.