Association Between the Vascular Calcification and High Turnover Radiographic Bone Changes in Chronic Kidney Disease Patients

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SP_021 Association Between the Vascular Calcification and High Turnover Radiographic Bone Changes in Chronic Kidney Disease Patients Virayavanich W, MD Department of Diagnostic and Therapeutic Radiology, Ramathibodi Hospital, Mahidol University, Rama VI Road, Ratchathewi, Bangkok 10400, Thailand E-mail: kaooat7@hotmail.com Category of the paper: Scientific paper

SP_021 Association Between the Vascular Calcification and High Turnover Radiographic Bone Changes in Chronic Kidney Disease Patients Corresponding author: Virayavanich W Co-authurs: Jaovisidha S, Disthabanchong S, Jenjitranant P Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Introduction Chronic kidney disease (CKD) is a worldwide health problem, which affects 5-10% of the world population In CKD patients, vascular calcification is a major cause of cardiovascular disease and associated with increased morbidity and mortality, especially in the dialysis patients (1-6)

Introduction Renal osteodystrophy (ROD) is a disorder of bone turnover or remodeling in the setting of CKD (4, 7, 8) There are 3 major patterns of bone response High-bone turnover - most common form Low-bone turnover Mixed osteodystrophy

Introduction The Kidney Disease Improving Global Outcomes (KDIGO) foundation Suggested relationship between mineral and bone disorder in CKD patients and defined a term CKD-MBD (Chronic kidney disease-mineral and bone disorder) = A systemic disorder of mineral and bone metabolism due to CKD

Introduction Previous studies in CKD patients: Some studies reported an inverse relationship between bone demineralization and vascular calcification (7, 9, 10) Other studies suggested a positive correlation between bone turn over and vascular calcification (1, 4)

Objectives To evaluate the association between vascular calcification and high turnover bone changes observed in pelvic and lumbosacral (LS) lateral spine radiographs in CKD patients

Methods Study population: Out-patient nephrology clinic of Ramathibodi Hospital during January 2009 - March 2012 Inclusion criteria: 1. Chronic hemodialysis patients who were eligible for kidney transplant (KT) waiting list 2. Age between 18-75 years 3. Available Pelvis AP and LS spine lateral radiographs

Methods Exclusion criteria: 1. Patients who had acute illnesses or acute kidney injury 2. A change in serum creatinine >15% within the past 3 months

Methods Demographic assessment: Patient s age, gender, underlying disease, clinical history Enrolled CKD patients Laboratory data: PTH level and serum calcium Radiographic assessment: Pelvis AP and lateral LS spine Bone change related to CKD Vascular calcification

Methods Radiographic assessment of bone changes related to CKD Subchondral bone resorption Sacroiliiac joints Pubic symphysis Subligamentous bone resorption Anteorsuperior iliac spine (ASIS) Anteroinferior iliac spine (AIIS) Ischial tuberosities Greater trochanter Lessor trochanter

Methods Radiographic assessment of bone changes related to CKD Subchondral bone resportion Sacroiliiac joint Pubic symphysis Irregular surface, adjacent reactive sclerosis or pseudo-widening

Methods Radiographic assessment of bone changes related to CKD Subligamentous bone resportion ASIS: Sartorius AIIS: Rectus femoris Greater trochanter: Gluteus medius & minimus Lesser trochanter: Iliopsoas tendon Ischial tuberosity: Hamstring tendons

Methods Radiographic assessment of vascular calcification Abdominal aortic calcification - using lateral lumbar spine radiograph Scored according to Kauppila et al method (Total score 0-24) (11-13) Pelvic vascular calcification (iliac and femoral arteries)- using pelvic radiograph Scored according to Adragao et al method (Total score 0-4) (14, 15) Total VC score = aortic calcification score (maximum score of 24) + (pelvic calcification score x 6) (maximum score of 24) Scored according to Vipattawat et al method (maximum score = 48) (16)

Radiographic assessment of aortic calcification Grading 0: no calcific deposits in front of the vertebra Methods L1 1: small scattered calcific deposits filling less than 1/3 of the longitudinal wall of the aorta L2 2: 1/3-2/3 of the wall calcified L4 L3 Level 3: 2/3 or more of the wall calcified Affected segment Score of the individual segments Posterior wall range 0-3 Anterior wall range 0-3 Composition score (AAC) Anterior-Posterior Severity range 0-6 L1 1 1 3 4 L2 1 2 2 4 L3 1 3 3 6 L4 1 0 3 3 Grading of calcification was assessed at the anterior and the posterior walls of the abdominal aorta adjacent to vertebrae L1-L4 Total 4 9 6 17 Maximum 4 12 12 24 Kauppila LI et.al. Nephrol Dial Transplant (2008) 23: 4009 15 ; Atherosclerosis. 1997 Jul 25;132(2):245-50

Radiographic assessment of pelvic calcification (Iliac and femoral arteries) Methods Divided into four sections by two imaginary lines: a horizontal line over the upper limit of both femoral heads and a median vertical line over the vertebral column Calcification score is the sum of the presence (1) or absence (0) of parallel linear calcifications in each section. In the example, pelvis score = 1+1+1+1 = 4 Adragao T. Nephrol Dial Transplant (2004) 19(6): 1480 8

Materials and methods Vascular calcification Total VC score (maximum score of 48) Aortic calcification score (maximum score of 24) Pelvic calcification score x 6 (maximum score of 24) Vipattawat K et al. Vascular calcification in long-term kidney transplantation. Nephrology. 2014 Apr;19(4):251-6

Results Table 1: Patient characteristics

Table 2: Radiographic bone changes in chronic hemodialysis patients Results

Table 3: Prevalence and severity of vascular calcification Results

Table 4: Association between vascular calcificationa and radiographic bone resorption in hemodialysis pateints Results

Results No significant correlation between radiographic bone change and age (p = 0.762) The vascular calcification Significant correlation with age (r = 0.496, p < 0.001) Not correlate with serum PTH level (r = 0.280, p = 0.761)

Discussion Our study: The association between CKD related bone changes and vascular calcification, using AP pelvic and lateral LS spine radiographs Routinely used for screening VC Modovan et al and Coen et al: The positive correlation between high bone turn over and VC in CKD patients Our study: The significant association between vascular calcification and subligamentous/subtendinous resorption No association between vascular calcification and subchondral bone resorption

Discussion The exact mechanisms of the relationship between bone turnover and vascular calcification is not clearly defined. Small number of positive radiographic bone changes Subchondral resorption (19.8%) & Subligamentous/subtendinous resorption (14%) Not represent all the CKD patients A positive correlation between age and vascular calcification The vascular calcification tends to increase in older patients

Discussion Limitation: Cross-sectional study Not determine the consequences of the developing vascular calcification and bone changes Need further longitudinal study Plain radiograph is less accurate and less sensitive than CT in detection of vascular calcification The vascular calcification scoring technique is not routinely used in our institution

Conclusions Chronic hemodialysis patients demonstrated significant association between vascular calcification and subligamentous/subtendinous resorption that encourages the pathologic link between bone changes related to high bone turn over and the vascular calcification in CKD patients

Conflict of interest The authors declare no conflict of interest

References 1. Coen G. Calcimimetics, parathyroid hormone, and vascular calcification in chronic kidney disease. Kidney international. 2008 Nov;74(10):1229-31. 2. Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM. Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circulation research. 2011 Sep 2;109(6):697-711. 3. Neven E, D'Haese PC. Vascular calcification in chronic renal failure: what have we learned from animal studies? Circulation research. 2011 Jan 21;108(2):249-64. 4. Moldovan D, Moldovan I, Rusu C, Racasan S, Patiu IM, Brumboiu A, et al. Vascular calcifications and renal osteodystrophy in chronic hemodialysis patients: what is the relationship between them? International urology and nephrology. 2011 Dec;43(4):1179-86. 5. Pai AS, Giachelli CM. Matrix remodeling in vascular calcification associated with chronic kidney disease. Journal of the American Society of Nephrology : JASN. 2010 Oct;21(10):1637-40. 6. Sinha S EH, Kalra PA. Vascular calcifiation: mechanisms and management. Br J Cardiol. 2008;15(6):316-20.

References 7. Moe SM. Vascular calcification and renal osteodystrophy relationship in chronic kidney disease. European journal of clinical investigation. 2006 Aug;36 Suppl 2:51-62. 8. Hruska KA, Teitelbaum SL. Renal osteodystrophy. The New England journal of medicine. 1995 Jul 20;333(3):166-74. 9. Persy V, D'Haese P. Vascular calcification and bone disease: the calcification paradox. Trends in molecular medicine. 2009 Sep;15(9):405-16. 10. Cannata-Andia JB, Roman-Garcia P, Hruska K. The connections between vascular calcification and bone health. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2011 Nov;26(11):3429-36. PubMed PMID: 22039012. 11. Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PW. New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis. 1997 Jul 25;132(2):245-50.

References 12. Bellasi A, Ferramosca E, Muntner P, Ratti C, Wildman RP, Block GA, et al. Correlation of simple imaging tests and coronary artery calcium measured by computed tomography in hemodialysis patients. Kidney international. 2006 Nov;70(9):1623-8. 13. Toussaint ND, Pedagogos E, Lau KK, Heinze S, Becker GJ, Beavis J, et al. Lateral lumbar X-ray assessment of abdominal aortic calcification in Australian haemodialysis patients. Nephrology. 2011 May;16(4):389-95. 14. Adragao T, Pires A, Branco P, Castro R, Oliveira A, Nogueira C, et al. Ankle-- brachial index, vascular calcifications and mortality in dialysis patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2012 Jan;27(1):318-25. 15. Adragao T, Pires A, Lucas C, Birne R, Magalhaes L, Goncalves M, et al. A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2004 Jun;19(6):1480-8. 16. Vipattawat K, Kitiyakara C, Phakdeekitcharoen B, Kantachuvesiri S, Sumethkul V, Jirasiritham S, et al. Vascular calcification in long-term kidney transplantation. Nephrology. 2014 Apr;19(4):251-6.