Vaszkuláris kalcifikáció krónikus veseelégtelenségben

Az előadások a következő témára: "Vaszkuláris kalcifikáció krónikus veseelégtelenségben"— Előadás másolata:

1 Vaszkuláris kalcifikáció krónikus veseelégtelenségben
Dr. Csiky Botond egyetemi docens / orvos-igazgató Pécsi Tudományegyetem ÁOK II. sz. Belgyógyászati Klinika és Nephrologiai Centrum / FMC Dialízis Centrum, Pécs

2 Vaszkuláris kalcifikáció krónikus veseelégtelenségben
Dr. habil. Csiky Botond PTE-ÁOK II. sz. Belgyógyászati Klinika és Nephrológiai Centrum FMC Dialízis Centrum Pécs

3 A csontrendszeren kívüli kalcifikáció a CKD következménye
B Key Points The images on these slides show calcifications at different sites in the body. A: X-ray showing severe soft-tissue calcification in the right index finger and wrist of one patient with secondary HPT. A 37-yr-old man on long-term haemodialysis developed a relapse of secondary HPT after subtotal parathyroidectomy.1 B: The radiograph of arterial media calcification (AMC) of the pelvic arteries taken from a study evaluating the prognostic value of AMC in predicting all-cause or cardiovascular mortality in stable haemodialysis patients.2 References Zerbi S, et al. J Clin Endocrinol Metab. 2008;93: London GM, et al. Nephrol Dial Transplant. 2003;18: Kok M, et al. Clin Nucl Med. 2003;28: A. Zerbi S, et al. J Clin Endocrinol Metab. 2008;93: ; B. London GM, et al. Nephrol Dial Transplant. 2003;18:

4 A kalcifikáció rizikófaktorai CKD betegek esetében
Életkor Diabetes Hiperfoszfatémia Dialízis ideje (hó) Lipidek Gyulladás Csökkent GFR Hiperkalcémia Pozitív kálcium egyensúly Key points: A number of risk factors exist that increase the likelihood of vascular calcification in CKD patients, including elevations in serum calcium and phosphorous.1,2 Several of the risk factors listed on this slide are believed to increase the risk of both arterial intimal and medial wall calcification, including advanced age, diabetes or glucose intolerance, and hyperphosphatemia.1,2 It is now recognized that inflammation is a pivotal component of intimal (atherosclerotic) calcification, and may also increase the severity of this condition.1 References: Goodman WG, London G. Am J Kidney Dis. 2004;43: London GM, et al. Nephrol Dial Transplant. 2003;18: Goodman WG, et al. Am J Kidney Dis. 2004;43: ; Kok M, et al. Clin Nucl Med. 2003;28(2): ; London GM, et al. Nephrol Dial Transplant. 2003;18: 4

5 Vaszkuláris kalcifikáció CKD betegekben
Vaszkuláris kalcifikáció az incidens dializált betegek 63–69%-ában van jelen.1 Key points: In a study of 129 patients initiating dialysis (incident patients), a measurement of coronary vascular calcification by electron computed tomography demonstrated that the majority (63–69%) of patients already had signs of vascular calcification at baseline.1 The baseline coronary vascular calcification measurements were taken prior to initiation of an open-label trial testing sevelamer or calcium-containing phosphate binders (RIND study).1 In a separate trial, a multivariable linear regression analysis was carried out in 170 maintenance haemodialysis patients attending one of 15 dialysis centers in the US or Europe with evidence of coronary artery calcification to determine whether any laboratory, demographic, or clinical variable could explain the significant extent of calcification seen in this population.2 A high prevalence of calcification of the coronary arteries, aorta, and cardiac valves was observed in the prevalent haemodialysis population study. Specifically, the degree of coronary artery calcification (CAC) observed was far greater than expected for age- and gender-matched individuals in the normal population, and the extent of CAC was significantly and independently associated with advanced age, male gender, diabetes, years on dialysis, and serum concentrations of calcium and phosphorous .2 In addition, the prevalence of preexisiting cardiovascular disease was proportional to the severity of vascular calcification.2 Linear regression analyses revealed that 1 mg/dL increases in phosphorous or calcium were associated with an elevated risk of vascular calcification in this population. These increases in phosphorous or calcium conferred the same risk of vascular calcification as seen after almost 2.5 years or > 5 years of dialysis, respectively.2 This study analysis was limited in that evaluation of the association between laboratory values and the extent of calcification was based on one baseline laboratory value for each laboratory parameter studied.2 References: Block GA, et al. Kidney Int. 2005;68: Raggi P, et al. J Am Coll Cardiol. 2002;39: 1Block GA, et al. Kidney Int. 2005;68: 5

6 Coronaria kalcifikáció krónikusan dializált betegekben
Key points: Kalpakian and Mehrotra recently summarized data from seven separate studies published between 2002 and 2005 evaluating patients on maintenance dialysis. Each study included the prevalence of detectable coronary artery disease in the population evaluated. The majority of patients in each study, from 53%–92%, exhibited detectable coronary artery calcification.1 Reference: Kalpakian MA, Mehrotra R. Semin Dial. 2007;20; N 37 205 71 43 104 53 101 % Diabetes Mellitus 0% 30% 34% 9% 38% 40% Kalpakian MA, Mehrotra R. Semin Dial. 2007;20: 6

7 Kalcifikációs Score– a dialízis időtartama alapján (év)
Coronaria kalcifikáció krónikus dialízis kezelésben részesülő fiatal felnőttekben Kalcifikációs Score– életkor alapján Kalcifikációs Score– a dialízis időtartama alapján (év) 10,000 1,000 100 10 1 0.1 Key points: Approximately 50% of deaths among adults undergoing regular dialysis is due to cardiovascular disease.1 The maintenance dialysis population also includes children and young adults (< 30 years of age), but less is known about the prevalence and extent of cardiovascular disease in this population.1 Using electron-beam computed tomography (EBCT) to screen for coronary artery calcification (CAC), Goodman and colleagues evaluated 39 patients (mean [±SD] age, 19 ± 7 years; range, 7 to 30) with ESRD on dialysis and 60 normal subjects (age 20–30).1 Both graphs on this slide refer solely to data from the 39 ESRD patients. As seen on the left-sided graph, the probability of calcification in ESRD patients increased as a function of age. None of the 23 ESRD patients younger than 20 years of age had evidence of CAC, but it was present in 14 of 16 patients 20–30 years of age. (Three out of 60 normal subjects had calcification).1 Compared to patients without calcification, patients with calcification were older (26 ± 3 vs 15 ± 5 years, P < 0.001) and had been undergoing dialysis for longer (14 ± 5 vs 4 ± 4 years, P < 0.001).1 The probability of calcification increased as a function of duration of dialysis as seen on the graph to the right.1 The stepped dashed line indicates the proportion of patients with evidence of coronary-artery calcification within each interval of approximately 4 years. The curved line reflects estimates derived by logistic-regression analysis.1 In addition, mean serum phosphorous and calcium-phosphorous product were higher in patients with CAC.1 Reference: Goodman WG, et al. N Engl J Med. 2000;342: N = 39 Szaggatott vonal: a coronaria calcificatioval rendelkező betegek aránya kb. 4 évres időszakonként.. Görbe: becslés (logisztikus-regressziós analízis alapján). „Fiatal felnőtt”: < 30 év. Coronaria kalcifikáció: EBCT Goodman WG. N Engl J Med. 2000;342: 7

8 CKD betegekben gyakori az intima és a media kalcifikáció egyaránt
Szövettan Atherosclerosis Diffúz morphologia. Calcium kristályok aggregációja Arteriosclerosis Linearis depozitumok az elasztikus lamellák mentén. A legsúlyosabb esetekben körkörösen kálcium kristályok denz rétege. Következmény Akut elzáródás (okklúzió) Vaszkuláris stiffness (non-okklúzív) Előfordulás Generalizált kardiovaszkuláris betegség CKD, diabetes (Monckeberg sclerosis) Kialakulás Lipid, makrofágok, vaszkuláris símaizom, gyulladás Elasztin, vaszkuláris símaizom Key points: There are two types of vascular calcification that occur in distinct areas of the artery wall, the intima and the media. These can be differentiated by histology, consequence, occurrence, and the type of cells and factors associated with them.1 Arterial intimal calcification occurs in atherosclerotic plaques. It can result in acute occlusion when the plaque ruptures.1 It is mainly observed in older patients with a history of diabetes and atherosclerosis and atherosclerotic complications before starting haemodialysis. It is associated with the typical risk factors of atherosclerotic disease.2 Arterial medial calcification occurs independently of intimal calcification and atherosclerosis. It is a non-occlusive condition. Medial vascular calcification leads to increased stiffness of the arterial wall and disturbances in blood flow, which can be assessed by aortic pulse wave velocity measurements.2,3 Medial calcification is observed in young and middle-aged CKD patients without conventional atherosclerotic risk factors and is closely associated with duration of haemodialysis and calcium phosphate disorders.2 CKD patients frequently exhibit both types of calcification.4 References: Proudfoot D, Shanahan CM. Herz. 2001;26: London GM, et al. Nephrol Dial Transplant. 2003;18: Raggi P, et al. Kidney Int. 2007;71: Giachelli CM. J Am Soc Nephrol. 2004;15: Proudfoot D, Shanahan CM. Herz. 2001;26: Giachelli CM. J Am Soc Nephrol. 2004;15: London GM, et al. Nephrol Dial Transplant. 2003;18: 8

9 A vaszkuláris kalcifikáció szabályozott folyamat
Az ér símaizom sejtek transzdifferenciálódásának mechanizmusa urémias körülmények következtében (in vivo és in vitro): RANKL kalcifikáció aktivátorai Osteoblast irányú differenciálódás inhibitorai Kalcifikálódó sejtek A hidroxiapatit vezikulumok nucleatioja A símaizom sejtek (VSMC) apoptosisa Mineralis imbalance Key points Evidence now suggests that vascular calcification is an active, regulated process, with many similarities to the process of skeletal mineralization,1 being the outcome of the active and dynamic balance of procalcifying and anticalcifying influences2 In this process, various proteins related to the control of bone and mineral metabolism are involved: down-regulation or perturbation of these proteins may lead to a phenotypic transformation of vascular smooth muscle cells (VSMCs) to osteo/chondrocytic-like calcifying cells1 Background A model of uraemic vascular calcification has been proposed1 An in vitro model of VSMCs has shown that a mineral imbalance can induce VSMC apoptosis The apoptotic bodies and vesicles can nucleate basic calcium (Ca) phosphate in the form of hyroxyapatite, the same mineral found in bone VSMC apoptosis also stimulates a host of changes in gene expression that are representative of an osteoblastic conversion of VSMCs and ultimately lead to vascular calcification Disturbances in mineral metabolism in the uraemic milieu, Ca-containing phosphate binders, and vitamin D treatment of secondary hyperparathyroidism may contribute to the pathogenesis of vascular calcification2 References 1. Shanahan CM. Clin Nephrol 2005;63:146–157 2. Derici U et al. Semin Dial 2006;9:60–68 Shanahan CM. Mechanisms of vascular calcification in renal disease. Clin Nephrol 2005;63:146–157 reproduced with permission from Dustri-Verlag Derici U and Meguid El Nahas A. Vascular Calcifications in Uremia: Old Concepts and New Insights. Semin Dial 2006;9:60–68, adapted with permission from Blackwell Publishing Shanahan CM. Clin Nephrol 2005;63:146–157 Derici U et al. Semin Dial 2006;19:60–68 Hidroxiapatit VSMC osteoblast phenotypussal

10 A vaszkuláris kalcifikáció lehetséges mechanizmusai
A Ca-P háztartás zavara Ca x P Sejthalál Apoptotikus testek és nekrotikus törmelék Gátló tényezők elvesztése Vaszkuláris kalcifikáció Csontképződés indukciója Ca/P-tartalmú matrix vezikulumok P Lipidek Gyulladásos cytokinek Egyéb Key points: Evidence suggests that multiple, non-mutually exclusive mechanisms of vascular calcification exist.1 Disordered Mineral Metabolism: Hyperphosphataemia and hypercalcaemia. Elevated serum calcium and phosphorous levels have been highly correlated with vascular calcification and are associated with all-cause and CVD mortality.1 As described earlier, in a study by Raggi et al., a 1 mg/dL increase in phosphorous or calcium conferred the same risk of vascular calcification as nearly 2.5 years (28.8 months) or > 5 years (63.5 months) of treatment with dialysis, respectively2 Loss of inhibition: Under normal conditions, inhibitory mechanisms exist to prevent spontaneous mineralization. Expression of a number of calcification inhibitors, such as matrix gla protein (MGP), pyrophosphate, osteopontin, and fetuin/2-HS-glycoprotein has been observed in healthy blood vessels. Under pathological conditions, a reduction in, or lack of these molecules, may lead to loss of inhibition and to vascular calcification.1,3 Induction of bone formation: Stimulation of vascular osteoblast/ chrondrocyte-like cells. Under mineralizing conditions (elevated Ca and/or P), smooth muscle cells (SMCs) undergo a phenotypic transition to gain osteogenic markers.1,3 Circulating Nucleational Complexes: Disordered bone turnover is a hallmark pathology of CKD. Elevated osteoclastic activity leads to release of circulating complexes that may serve to nucleate mineral deposition.1,3 Cell death: eg, due to increased intracellular phosphate levels. Dying cells become highly permeable to calcium and phosphate. Cell death provides phospholipid-rich membranous debris and apoptotic bodies that may act to nucleate calcium-phosphate deposition.1,3 References: Giachelli CM. J Am Soc Nephrol. 2004;15: Raggi P, et al. J Am Coll Cardiol. 2002;39: Speer MY. Cardiovasc Pathol. 2004;13:63-70. Keringő nucleatios komplexek Csont remodeling Adapted from Giachelli CM. J Am Soc Nephrol. 2004;15: 10

11 Vaszkuláris kalcifikáció és mortalitás dializált betegekben
1.00 NC NC = nincs kalcifikáció (n = 73) 0.75 P < 0.001 Összmortalitás 0.50 AMC AMC = arteria media kalcifikáció (n = 54) P < 0.01 0.25 AIC 0.00 AIC = arteria intima kalcifikáció (n = 75) 25 50 75 100 1.00 NC P < 0.01 0.75 Key points: A number of studies have linked arterial calcification with cardiovascular morbidity and mortality in CKD patients. However, most have not differentiated between type of calcification (ie, intimal versus medial). London and colleagues differentiated between these two types of calcification in a study of 202 maintenance haemodialysis patients using soft-tissue native radiograms of the pelvis and thigh.1 The presence and type of arterial calcification was evaluated for its prognostic value in predicting all-cause or cardiovascular mortality.1 According to their analyses, arterial intimal (AIC) and medial (AMC) calcification were both associated with an increased risk in all-cause and cardiovascular mortality.1 Background: Of the 73 deaths that occurred during the follow-up period, 46 were due to cardiovascular causes.1 All-cause mortality was independently and significantly associated with calcification: Risk ratios (RRs) for the AMC versus no calcification (NC) group was 15.7 (4.8–51.4; P < ) and for the AIC versus NC group was 4.85 (1.68–14.10; P = ).1 Similarly, cardiovascular mortality was independently and significantly associated with calcification: RR for the AMC versus NC group was 45.7 (9.75–213.0; P < ) and for the AIC versus NC group was 7.50 (1.59–35.5; P = ).1 In this study, intimal calcification was predominantly observed in older patients with a history of diabetes and atherosclerosis and atherosclerotic complications before starting haemodialysis. It was additionally associated with typical risk factors associated with atherosclerotic disease.1 Medial calcification was observed in young and middle-age patients without conventional atherosclerotic risk factors and was closely associated with duration of haemodialysis and calcium phosphate disorders.1 Reference: London GM, et al. Nephrol Dial Transplant. 2003;18: AMC Kardiovaszkuláris mortalitás 0.50 P < 0.001 AIC 0.25 0.00 25 50 75 100 N = 202 Idő (hónap) London GM,. Nephrol Dial Transplant. 2003;18: 11

12 Arteria femoralis superficialis kalcifikációja ESRD betegekben és 24 hónapos túlélés
Key points: This prospective study of 60 haemodialysis, 28 peritoneal dialysis, and 46 CKD stage 4 patients in one UK center evaluated calcification of the superficial femoral artery as measured by multislice computer tomography (CT).1 Each CT slice was scored individually, and a calcification score (CaSc) generated.1 CT of the superficial femoral artery and measurement of haemodynamic variables were performed at baseline, 12 and 24 months.1 Of the 134 patients evaluated, 20 of the 21 who died during the study had vascular calcification and 40% of deaths were due to cardiovascular-related causes.1 As seen in this figure, calcification was associated with increased risk of all-cause mortality.1 Cox proportional hazard analysis identified that the change in CaSc from baseline to 12 months was significantly associated with reduced survival, P = Interestingly, 4% to 8% of patients demonstrated regression of vascular calcification over the study period demonstrating that vascular calcification is a dynamic process. This process may provide opportunities for therapeutic intervention.1 Background: The small number of patients evalulated is a limitation of this study.1 Reference: Sigrist MK, et al. Clin J Am Soc Nephrol. 2007:2; Nem kalcifikált Kalcifikált N = 134 (60 HD, 28 CAPD, 46 CKD st 4.) Sigrist MK. Clin J Am Soc Nephrol.2007; 2:1241–1248. 12

13 A kardiovaszkuláris kalcifikáció szorosan összefügg a mortalitással dializált betegekben
*Calcification score from 0 (absence of calcium deposit) to 4 (calcifications present in all arterial segments examined). Blacher J, et al. Hypertension. 2001;38:

14 EBCT Amgen Confidential Information - Do Not Distribute

15 50%-70% RR intervallum

16 Spiral/Multidetektoros CT

17 Spiral/Multidetektoros CT
2-4 szelet 8-16 szelet 16-32 szelet 32-64 szelet 64 x 2 szelet 256 szelet 320 szelet

18 Az Agatston score Jelentett variabilitás 8-10%
2 4 3 Kalcifikált plakk area=A; density=D 2 Ér lumen Denzitás = 130–200; koefficiens 1 Denzitás = 201–300; koefficiens Agatston score = A x Dcoef Denzitás = 301–400; koefficiens 3 Denzitás >401; koefficiens 4 Jelentett variabilitás 8-10%

19 Kálcium volumen score Jelentett variabilitás 5-6% d y A B 0.56 mm x z
DA x (1–d) + (DB x d) 130 HU included (orange) 130 HU excluded (red) DA, density in A; DB, density in B Jelentett variabilitás 5-6% Callister et al. Radiology 1998;208:807–814

20 A kiindulási CAC score az összmortalitás prediktora dializált betegekben
Shantouf et al. Am J Nephrol. 2010;31:

21 Vaszkuláris kalcifikáció: összefoglalás
A vaszkuláris kalcifikáció korán jelentkezik – a legtöbb dializált betegben kimutatható. Az intima és a media kalcifikáció két különböző entitás, de mindkettőt gyakran (akár egyidejűleg is) látjuk ezekben a betegekben. A vaszkuláris kalcifikáció mechanizmusa komplex. A vaszkuláris kalcifikáció a mortalitás rizikójának növekedésével jár krónikus vesebetegkben. References: Block GA, et al. Kidney Int. 2005;68: Kalpakian MA, Mehrotra R. Semin Dial. 2007;20; Proudfoot D, Shanahan CM. Herz. 2001;26: Giachelli, CM. J Am Soc Nephrol. 2004;15: Speer MY, Giachelli CM. Cardiovasc Pathol. 2004;13:63-70. London GM, et al. Nephrol Dial Transplant. 2003;18: Sigrist MK, et al. Clin J Am Soc Nephrol. 2007;2: Blacher J, et al. Hypertension. 2001;38: Block GA. Kidney Int. 2005;68: Kalpakian MA. Semin Dial. 2007;20; Proudfoot D. Herz. 2001;26: Giachelli CM. J Am Soc Nephrol. 2004;15: London GM. Nephrol Dial Transplant. 2003;18: Sigrist MK. Clin J Am Soc Nephrol. 2007;2: Blacher J. Hypertension. 2001;38: 21

22 Vaszkuláris kalcifikáció és hyperparathyreosis
A vaszkuláris kalcifikáció kialakulásához hozzájárul: A csontanyagcsere zavara Magas Ca és P szint Secunder hyperparathyreosis (SHPT) SHPT kezelése Cinacalcet SHPT hatékony kezelése – PTH szint csökkentése Ca és P szintet is csökkenti A CKD állatmodelljeiben a calcimimeticumok lassítják a vascularis calcificatiot CT általánosan használt a vaszkuláris kalcifikáció objektív mérésre

23 McCullough PA et al. Arch Intern Med. 2009;169(22):2064-2070

24 CAC átlagos progressziója évente
klinikai vizsgálatok alapján McCullough PA et al. Arch Intern Med. 2009;169(22):

25 Effects of cinacalcet on vascular calcification in hemodialysis patients (J Almiral)
N=11; chr HD, secunder hyperparathyreosis Th: Cinacalcet / átlagos dózis: 50±22 mg/nap

26 CAC score átlagos éves progressziója: 8%
Effects of cinacalcet on vascular calcification in hemodialysis patients (J Almiral) N=11; chr HD, secunder hyperparathyreosis Th: Cinacalcet / átlagos dózis: 50±22 mg/nap CAC score átlagos éves progressziója: 8%

27 Csak egy randomizált klinikai vizsgálat szolgáltathat evidenciát arra, hogy az SHPT specifikus kezelése hogyan hat a vaszkuláris kalcifikáció progressziójára.

28 A randomizeD VAscular calcificatioN study to evaluate the effects of CinacalcEt

29

30 Hipotézis Cinacalcet-et és kisdózisú D-vitamint tartalmazó
kezelés lassítja a coronaria arteria kalcifikáció (CAC) progresszióját egy év alatt a hagyományos kezeléshez* képest kálcium-tartalmú foszfátkötővel kezelt hemodializált betegekben. Data on file, Amgen; [ADVANCE Protocol ; 6/22/2007]. *Hagyományos kezelés = D-vitamin + foszfátkötő, ha szükséges. Raggi P et al. Poster presented at the 2010 Clinical Meeting of the National Kidney Foundation, Orlando, FL, April 13-17, 2010. Floege J et al. Poster presented at the 2010 ISN Nexus Meeting, Kyoto, Japan, April 15-18, 2010. 30

31 Vizsgálati végpontok Elsődleges végpont Secondary Endpoints
Percentage change from baseline in CAC score at week 52 Elsődleges végpont Secondary Endpoints A CAC score százalékos változása az 52. héten. Másodlagos végpontok Abszolut változás a CAC score-ban az 52. héten Abszolut és százalékos változás a kiindulási értékhez képest: aorta kalcifikációban az 52. héten aorta és mitrális billentyű kalcifikációban az 52. héten laboratóriumi paraméterekben a vizsgálat végén ( hét) Azon betegek aránya, akiknél a CAC score progressziója > 15% az 52. héten Biztonságosság Data on file, Amgen [ADVANCE Protocol ; 6/22/2007]. Laboratory parameters = PTH, calcium, phosphorus and Ca x P Safety = nature, frequency, severity and relationship to treatment of adverse events Inclusion Criteria Informed Consent Adults ≥ 18 years of age On hemodialysis for ≥ 3 months prior to study day 1 iPTH > 300 pg/mL (31.8 pmol/L) OR iPTH  150 pg/mL and ≤ 300 pg/mL (15.9 – 31.8 pmol/L) and receiving treatment with vitamin D analogs at time of PTH assessment and corrected serum Ca x P > 50 mg2/dL2 (3.9 mmol2/L2) Corrected serum Ca ≥ 8.4 mg/dL (2.1 mmol/L) Screening CAC score ≥ 30 Subjects were subsequently stratified: ≥ 30–399, ≥ 400–999, and ≥ 1000 Concomitenet Therapy Changes in active vitamin D brand were to be avoided Calcium-containing phosphate binders Were to remain as stable as possible Best practice guidelines were to be followed Dialysate calcium concentration and cholesterol-lowering medications were to remain stable throughout study Not permitted Non–calcium containing phosphate binders [sevelamer HCl, lanthanum carbonate, aluminum-based phosphate binders]* Non-study cinacalcet Other investigational agents Raggi P et al. Poster presented at the 2010 Clinical Meeting of the National Kidney Foundation, Orlando, FL, April 13-17, 2010. Floege J et al. Poster presented at the 2010 ISN Nexus Meeting, Kyoto, Japan, April 15-18, 2010.

32 Betegek 737 beteget szűrtek és 360 beteget randomizáltak, 180 beteget csoportonként. Átlag életkor 61.5 ± 12.7 év, 58% férfi és 24% fekete Hemodialízis kezelésben töltött median (P10, P90) idő 36.7 (9.5, 107.0) hó. A végső analízisre 235 beteg esetében került sor: 115 beteg: cinacalcet + kisdózisú D-vitamin 120 beteg: rugalmasan adagolt D-vitamin Kisdózisú D-vitamin: Iv 0.5 μg calcitriol , 1 μg alfacalcidol, 1 μg doxecalciferol vagy 2 μg paricalcitol dialízis kezelésenként ill. oralisan 0.25 μg calcitriol másnaponta vagy 0.25 alfacalcidol naponta. Raggi P et al. Poster presented at the 2010 Clinical Meeting of the National Kidney Foundation, Orlando, FL, April 13-17, 2010. Floege J et al. Poster presented at the 2010 ISN Nexus Meeting, Kyoto, Japan, April 15-18, 2010.

33 A vizsgálat felépítése

34 Kardiovazkuláris kalcifikációs score a vizsgálat kezdetén
Anatomiai hely Agatston score† Median (P10, P90) Volumen score, ‡ mm3 Cinacalcet (n=115) Kontroll (n=120) kontroll Coronaria 695 (98, 1959) 590 (71, 2583) 464 (94, 1565) 466 (77, 1968) Aorta thoracica 2114 (8, 14836) 1552 (9, 8097) 1706 (9, 11691) 1329 (16, 6014) Aorta billentyű 2 (0, 907) 0 (0, 281) 4 (0, 710) 0 (0, 218) Mitralis billentyű 0 (0, 1125) 6 (0, 978) 0 (0, 973) 12 (0, 887) Agatston: Table Volume: Table *patients with a calcium score of zero on the original scale or a calcium volume score of zero on the original scale have been assigned a value of zero on the base2 log scale (ie, a value of one on the original scale). †The total coronary calcification score is based on the sum of the scores from the left main, left anterior descending, circumflex, and right coronary scores. ‡The total coronary artery calcium volume score includes the calcium volume for the left main, left anterior descending, circumflex, and right coronary arteries. Efficacy Evaluable Analysis Set †The total coronary calcification score is based on the sum of the scores from the left main, left anterior descending, circumflex, and right coronary scores. ‡The total coronary artery calcium volume score includes the calcium volume for the left main, left anterior descending, circumflex, and right coronary arteries. Efficacy Evaluable Analysis Set Raggi P et al. Poster presented at the 2010 Clinical Meeting of the National Kidney Foundation, Orlando, FL, April 13-17, 2010. Floege J et al. Poster presented at the 2010 ISN Nexus Meeting, Kyoto, Japan, April 15-18, 2010.

35 Laboratóriumi parametérek a vizsgálat kezdetén
Cinacalcet N=115 Kontroll N=120 Összes beteg N=235 PTH , pg/mL Átlag (P10, P90) 417 (239, 1045) 412 (265, 1091) 413 (247, 1046) Korrigált szérum kálcium, mg/dL Átlag (SD) mmol/l 9.4 (0.7) 2.4 (0.2) 9.3 (0.5) 2.3 (0.1) 9.3 (0.6) Szérum foszfát, mg/dL 6.1 (1.9) 2.0 (0.6) 5.4 (1.7) 1.8 (0.6) 5.8 (1.8) Korrigált Ca x P, mg2/dL2 mmol²/l² 56.8 (17.4) 4.6 (1.4) 50.4 (16.0) 4.1 (1.3) 53.5 (17.0) Table: To come Raggi P et al. Poster presented at the 2010 Clinical Meeting of the National Kidney Foundation, Orlando, FL, April 13-17, 2010. Floege J et al. Poster presented at the 2010 ISN Nexus Meeting, Kyoto, Japan, April 15-18, 2010.

36 Kiindulási paraméterek
Viszonylag jól kiegyensúlyozottak a két betegcsoport között. A betegek megoszlása a szűréskor mért CAC score alapján felállított csoportokba (≥ 30 to 399, ≥ 400 to 999, and ≥ 1000) kiegyensúlyozott volt a vizsgálat két ágában. Raggi P et al. Poster presented at the 2010 Clinical Meeting of the National Kidney Foundation, Orlando, FL, April 13-17, 2010. Floege J et al. Poster presented at the 2010 ISN Nexus Meeting, Kyoto, Japan, April 15-18, 2010.