Abstract
Background
Coronary calcifications (CC) portend increased mortality in adults receiving hemodialysis (HD), however the risk factors associated with CC progression are not well known in pediatric patients. Our previous cross-sectional studies demonstrated high CC prevalence (31 %) in pediatric patients, which were significantly associated with high serum phosphorus (P), fibroblast growth factor 23 (FGF) levels, dialysis vintage, and low cholesterol. The current study was undertaken to determine and elucidate CC progression in pediatric HD patients.
Methods
A 1-year prospective longitudinal study of 16 pediatric patients (ten male; mean age, 16.9 ± 3 years; range, 10.1–20.4 years) receiving chronic HD was conducted.
Results
CC were observed in five of 16 (31.3 %) patients on baseline computed tomogram (CT) scan; 14/16 patients underwent 1-year CT. All patients with initial CC who completed CT at 1 year (3/5) progressed; one patient had new CC and none of the patients had resolved CC. Mean Agatston score increased from 23.4 ± 18.06 HU (baseline) to 169 ± 298.9 HU. Patients with CC progression had higher mean serum P (8.6 ± 1.8 mg/dl vs. 6.3 ± 1.1 mg/dl, p = 0.015) and FGF 23 levels (3,994 ± 860.5 pg/ml vs. 2,327 ± 1,206.4 pg/ml, p = 0.028). Serum P and FGF 23 levels were positively correlated with final Agatston scores (R = 0.65, p = 0.01 for serum P and R = 0.54, p = 0.045 for FGF 23) and change in Agatston scores (R = 0.65, p = 0.01 for serum P and R = 0.52, p = 0.048 for FGF 23).
Conclusions
Our study shows that CC is progressive in pediatric patients receiving HD and that increased serum P and FGF 23 levels are associated with this progression.
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References
Sarnak MJ, Levey AS (2000) Cardiovascular disease and chronic renal disease: a new paradigm. Am J Kidney Dis 35:S117–131
McDonald SP, Craig JC (2004) Long-term survival of children with end-stage renal disease. N Engl J Med 350:2654–2662
Parekh RS, Carroll CE, Wolfe RA, Port FK (2002) Cardiovascular mortality in children and young adults with end-stage kidney disease. J Pediatr 141:191–197
Kopple JD (2005) The phenomenon of altered risk factor patterns or reverse epidemiology in persons with advanced chronic kidney failure. Am J Clin Nutr 81:1257–1266
Kalantar-Zadeh K, Ikizler TA, Block G, Avram MM, Kopple JD (2003) Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences. Am J Kidney Dis 42:864–881
(2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl:S1-130.
Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15:827–832
Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM (2007) Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int 71:438–441
Block GA, Spiegel DM, Ehrlich J, Mehta R, Lindbergh J, Dreisbach A, Raggi P (2005) Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 68:1815–1824
Civilibal M, Caliskan S, Adaletli I, Oflaz H, Sever L, Candan C, Canpolat N, Kasapcopur O, Kuruoglu S, Arisoy N (2006) Coronary artery calcifications in children with end-stage renal disease. Pediatr Nephrol 21:1426–1433
Shroff RC, Donald AE, Hiorns MP, Watson A, Feather S, Milford D, Ellins EA, Storry C, Ridout D, Deanfield J, Rees L (2007) Mineral metabolism and vascular damage in children on dialysis. J Am Soc Nephrol 18:2996–3003
Srivaths PR, Silverstein DM, Leung J, Krishnamurthy R, Goldstein SL (2010) Malnutrition-inflammation-coronary calcification in pediatric patients receiving chronic hemodialysis. Hemodial Int 14:263–269
Srivaths PR, Goldstein SL, Silverstein DM, Krishnamurthy R, Brewer ED (2011) Elevated FGF 23 and phosphorus are associated with coronary calcification in hemodialysis patients. Pediatr Nephrol 26:945–951
Chertow GM, Burke SK, Raggi P (2002) Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 62:245–252
Raggi P, Bommer J, Chertow GM (2004) Valvular calcification in hemodialysis patients randomized to calcium-based phosphorus binders or sevelamer. J Heart Valve Dis 13:134–141
Raggi P, Boulay A, Chasan-Taber S, Amin N, Dillon M, Burke SK, Chertow GM (2002) Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease? J Am Coll Cardiol 39:695–701
Sigrist MK, Taal MW, Bungay P, McIntyre CW (2007) 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 2:1241–1248
Civilibal M, Caliskan S, Kurugoglu S, Candan C, Canpolat N, Sever L, Kasapcopur O, Arisoy N (2009) Progression of coronary calcification in pediatric chronic kidney disease stage 5. Pediatr Nephrol 24:555–563
van Husen M, Fischer AK, Lehnhardt A, Klaassen I, Moller K, Muller-Wiefel DE, Kemper MJ (2010) Fibroblast growth factor 23 and bone metabolism in children with chronic kidney disease. Kidney Int 78:200–206
Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592
Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB (2000) Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342:1478–1483
Moe SM, O’Neill KD, Reslerova M, Fineberg N, Persohn S, Meyer CA (2004) Natural history of vascular calcification in dialysis and transplant patients. Nephrol Dial Transplant 19:2387–2393
Schankel K, Robinson J, Bloom RD, Guerra C, Rader D, Joffe M, Rosas SE (2007) Determinants of coronary artery calcification progression in renal transplant recipients. Am J Transplant 7:2158–2164
Shroff RC, McNair R, Figg N, Skepper JN, Schurgers L, Gupta A, Hiorns M, Donald AE, Deanfield J, Rees L, Shanahan CM (2008) Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis. Circulation 118:1748–1757
Mathew S, Lund RJ, Strebeck F, Tustison KS, Geurs T, Hruska KA (2007) Reversal of the adynamic bone disorder and decreased vascular calcification in chronic kidney disease by sevelamer carbonate therapy. J Am Soc Nephrol 18:122–130
Isakova T, Gutierrez OM, Chang Y, Shah A, Tamez H, Smith K, Thadhani R, Wolf M (2009) Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol 20:388–396
Kuro-o M (2010) Overview of the FGF23-Klotho axis. Pediatr Nephrol 25:583–590
Razzaque MS (2009) The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis. Nat Rev Endocrinol 5:611–619
Jean G, Bresson E, Terrat JC, Vanel T, Hurot JM, Lorriaux C, Mayor B, Chazot C (2009) Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant 24:948–955
Balci M, Kirkpantur A, Gulbay M, Gurbuz OA (2010) Plasma fibroblast growth factor-23 levels are independently associated with carotid artery atherosclerosis in maintenance hemodialysis patients. Hemodial Int 14:425–432
Gutierrez OM, Januzzi JL, Isakova T, Laliberte K, Smith K, Collerone G, Sarwar A, Hoffmann U, Coglianese E, Christenson R, Wang TJ, deFilippi C, Wolf M (2009) Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 119:2545–2552
Mirza MA, Larsson A, Melhus H, Lind L, Larsson TE (2009) Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. Atherosclerosis 207:546–551
Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, Gutierrez OM, Aguillon-Prada R, Lincoln J, Hare JM, Mundel P, Morales A, Scialla J, Fischer M, Soliman EZ, Chen J, Go AS, Rosas SE, Nessel L, Townsend RR, Feldman HI, St John Sutton M, Ojo A, Gadegbeku C, Di Marco GS, Reuter S, Kentrup D, Tiemann K, Brand M, Hill JA, Moe OW, Kuro OM, Kusek JW, Keane MG, Wolf M (2011) FGF23 induces left ventricular hypertrophy. J Clin Invest 121:4393–4408
Wolf M (2012) Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int 82:737–747
Lim K, Lu TS, Molostvov G, Lee C, Lam FT, Zehnder D, Hsiao LL (2012) Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation 125:2243–2255
Khan AM, Chirinos JA, Litt H, Yang W, Rosas SE (2012) FGF-23 and the progression of coronary arterial calcification in patients new to dialysis. Clin J Am Soc Nephrol 7:2017–2022
Nigwekar SU, Bhan I, Thadhani R (2012) Ergocalciferol and cholecalciferol in CKD. Am J Kidney Dis 60:139–156
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Srivaths, P.R., Goldstein, S.L., Krishnamurthy, R. et al. High serum phosphorus and FGF 23 levels are associated with progression of coronary calcifications. Pediatr Nephrol 29, 103–109 (2014). https://doi.org/10.1007/s00467-013-2575-8
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DOI: https://doi.org/10.1007/s00467-013-2575-8