Vascular calcification in stage 5 Chronic Kidney Disease patients on dialysis

Transcription

1 Vascular calcification in stage 5 Chronic Kidney Disease patients on dialysis Seoung Woo Lee Div. Of Nephrology and Hypertension, Dept. of Internal Medicine, Inha Unv. College of Medicine, Inchon, Korea

2 Case Female, 61 years-old CC : general weakness, poor intake x 3 weeks PHx : ESRD 1990 ( IgA nephropathy) CAPD for 10 years Transfer to HD via AV graft (brachiocephalic) due to CAPD peritonitis in 2002 Transfer to Inha Univ. Hospital Angioplasty due to AVG obstruction x 3 Sclerosing encapsulating peritonitis, 2002 Admission several times due to poor intake, abdominal pain

3 Laboratory data CBC: K BUN/Cr : 78.1/ 8.2 mg/dl Ca/P : 11.2 / 6.8 mg/dl Total cholesterol : 184 mg/dl HDL-cholesterol : 30 mg/dl Albumin : 2.8 g/dl Intact PTH : 45.9 pg/nl Lipoprotein (a) : 67.5 mg/dl

4 Mg/dL 12.0 Total calcium Inorganic phosphate Changes of total calcium and phosphate

5 Chest PA

6 KUB

7 Femoral angiography

8

9

10

11

12

13

14

15

16

17

18

19

20 Abdomen-pelvis CT

21 Hospital course HD # 4: acute respiratory failure due to CO 2 narcosis HD # 10: ischemic pain and bluish changes in color on left 1 st toe Angiography: Angioplasty failed Femoro- bypass graft failed Ischemic necrosis of left lower leg, up to knee level HD # 93 : necrosis of right 1 st, 5 th toe HD # 111: expired

22 CKD5 patient on hemodialysis

23 Arterial calcification in stage 5 chronic kidney disease (CKD5) patients on dialysis Why problem? Increase in long-term CKD5 patients on dialysis DM, Hypertension, old age CKD5 High risk group for arterial calcification and cardiovascular disease Accelerated atherosclerosis in CKD5 Uremia-associated risk factors, classic risk factors Complicated with the management of calcium and phosphate, secondary hyperparathyroidism Mechanism of arterial calcification Management

24 Lindner A, et al. Accelerated atherosclerosis in prolonged Maintenance hemodialysis. N Engl J Med 1974; 290:

25 London GM, et al. Curr Opin Nephrol Hypertens 2005; 14: 525

26 Cardiovascular calcification and CVD mortality in ESRD Risk of CVD mortality in adults with ESRD times higher than that of general population Hyperphosphatemia and elevated Ca x P product Promote vascular calcification Significantly linked to all cause and CVD mortality in ESRD patients

27 Coronary-artery calcification in young adults with ESRD who are undergoing dialysis Goodman J, et al. N Engl J Med 2000; 342: 1478

28 Goodman J, et al. N Engl J Med 2000; 342: 1478

29 Goodman J, et al. N Engl J Med 2000; 342: 1478

30 Raggi P, et al. J Am Coll Cardiol 2002; 39: 695

31 London GM, et al. NDT 2003; 18; 1731

32 Moe S. KI 2006; 70:1535

33

34

35 Nemeth E.

36

37

38 Moe S, e t al. KI 2006

39 Both secondary hyperparathyroidism and adynamic bone Linked to adverse clinical outcomes among patients undergoing dialysis Soft tissue and vascular calcification Skeletal fracture

40 Adynamic bone Adversely affects systemic calcium homeostasis Increase the risk of soft tissue and vascular calcification Due to reduction in the capacity of the skeleton to buffer calcium entering ECF from GI tract or from dialysate

41 Adynamic bone Serum calcium concentration and episodes of hypercalcemia Higher than other types of renal bone diseases Arterial calcification score Greater in patients with relatively low plasma PTH levels and histomorphometric features of adynamic bone Salusky IB, et al. KI 1994 London GM,e t al. JASN 2004

42 Mechanisms of vascular calcification Giachelli CM. JASN 2004; 15: 2959

43 Giachelli CM. JASN 2004; 15: 2959

44 Cozzolino M, et al. KI 2005; 68: 429

45 Can vascular calcification be controlled? Restrict calcium-containing phosphate binder and use of non-calcium-containing P binders Sevelamer, Lanthanum Bisphosphonate Anti-hypertensives Control of secondary hyperparathyroidism Reversal of adynamic bone disease

46 Restrict calcium-containing phosphate binder intake of less than 1.5 g/day Should not be used in patients with low ipth hormone level or evidence of vascular calcification Use of non-calcium-containing P binders Sevelamer Lanthanum

47

48 Salusky IB. KI 2006

49 Sevelamer attenuates the progression of coronary calcification In HD patients Chertow GM, et al. KI 2002; 62: 245

50

51

52 Mathew S, et al. JASN 2007

53

54

55 Price PA, et al. KI 2006; 70:1577

56 Price PA, et al. KI 2006; 70:1577

57 Anti-hypertensive agents Calcium channel blocker Endothelin(ET-1) receptor antagonist Angiotensin II blocker

58 Nifedipine slows down progression of coronary calcification in hypertensive Patients compared with diuretics Motro, Shemesh. Hypertension. 2001

59 Aortic calcification WK: warfarin, vitamin K1, DAR: ET-antagonist, IRB: ATII blocker HCTZ: thiazide Dao HH, et al. J Hypertens 2002

60 Control of secondary hyperparathyrodism Use active form of vitamin D Use of calcimimetics Cinacalcet Reversal of adynamic bone disease By reducing dialysate calcium concentration

61

62

63

64

65 1.62 mm 1.0 mm Harris A, et al. KI 2006

66 Harris A, et al. KI 2006

67 Harris A, et al. KI 2006

68 Summary Vascular calcification is highly correlated with CVD morbidity and mortality, especially in high-risk populations such as ESRD or DM. Derangements in calcium and phosphate metabolism effect by elevating Ca x P product, and also by direct effects on smooth muscle cells that promote bonelike differentiation. The challenge remains to develop therapeutic strategies that may prevent and potentially reverse vascular calcification.