Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Pediatric Nephrology
Published in: Pediatric Nephrology 1/2019

01-01-2019 | Review

Pathophysiology and treatment of cardiovascular disease in pediatric chronic kidney disease

Authors: Nadine Khouzam, Katherine Wesseling-Perry

Published in: Pediatric Nephrology | Issue 1/2019

Login to get access

Abstract

Life expectancy in patients with all stages of chronic kidney disease (CKD) falls far short of that in the general population. Cardiovascular disease is the leading cause of mortality in pediatric patients with CKD. In contrast to the intimal atherosclerotic lesions that characterize cardiovascular disease in the general population, vascular endothelial dysfunction, medial arterial calcification, and cardiac dysfunction contribute to cardiovascular pathological conditions in CKD. The pathogenesis of these lesions, the origins of which can be identified in the absence of traditional cardiovascular risk factors, is incompletely understood. CKD-mediated vascular calcification in CKD is characterized by a transition of vascular smooth muscle cells to an osteoblast-like phenotype and altered bone and mineral metabolism are strongly linked to progressive cardiovascular disease in this population. Renal osteodystrophy therapies, including phosphate binders, vitamin D analogs, and calcimimetics, have an impact on the progression of cardiovascular disease. However, cardiovascular disease has its origins before the development of secondary hyperparathyroidism, and optimal therapeutic regimens that minimize cardiac dysfunction, vascular calcification, and early mortality remain to be defined.
Literature
1.
2.
Mitsnefes MM (2005) Cardiovascular disease in children with chronic kidney disease. Adv Chronic Kidney Dis 12:397–405PubMedCrossRef
3.
Groothoff JW, Lilien MR, van de Kar NC, Wolff ED, Davin JC (2005) Cardiovascular disease as a late complication of end-stage renal disease in children. Pediatr Nephrol 20:374–379PubMedCrossRef
4.
Gruppen MP, Groothoff JW, Prins M, van der WP, Offringa M, Bos WJ, Davin JC, Heymans HS (2003) Cardiac disease in young adult patients with end-stage renal disease since childhood: a Dutch cohort study. Kidney Int 63:1058–1065PubMedCrossRef
5.
Rees L, Shroff R, Hutchinson C, Fernando ON, Trompeter RS (2007) Long-term outcome of paediatric renal transplantation: follow-up of 300 children from 1973 to 2000. Nephron Clin Pract 105:c68–c76PubMedCrossRef
6.
Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF, American College of Cardiology/American Heart Association Task Force on Practice (2014) 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation 129:S1–45PubMedCrossRef
7.
Wanner C, Krane V, Marz W, Olschewski M, Mann JF, Ruf G, Ritz E (2005) Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 353:238–248PubMedCrossRef
8.
London GM, Marty C, Marchais SJ, Guerin AP, Metivier F, de Vernejoul MC (2004) Arterial calcifications and bone histomorphometry in end-stage renal disease. J Am Soc Nephrol 15:1943–1951PubMedCrossRef
9.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group (2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int 76:s1–s130
10.
Schaefer F, Doyon A, Azukaitis K, Bayazit A, Canpolat N, Duzova A, Niemirska A, Sozeri B, Thurn D, Anarat A, Ranchin B, Litwin M, Caliskan S, Candan C, Baskin E, Yilmaz E, Mir S, Kirchner M, Sander A, Haffner D, Melk A, Wuhl E, Shroff R, Querfeld U, Consortium CS (2017) Cardiovascular phenotypes in children with CKD: the 4C study. Clin J Am Soc Nephrol 12:19–28PubMedCrossRef
11.
Barletta GM, Flynn J, Mitsnefes M, Samuels J, Friedman LA, Ng D, Cox C, Poffenbarger T, Warady B, Furth S (2014) Heart rate and blood pressure variability in children with chronic kidney disease: a report from the CKiD study. Pediatr Nephrol 29:1059–1065PubMedPubMedCentralCrossRef
12.
Mitsnefes MM, Kimball TR, Border WL, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2004) Impaired left ventricular diastolic function in children with chronic renal failure. Kidney Int 65:1461–1466PubMedCrossRef
13.
Mitsnefes MM, Kimball TR, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2003) Left ventricular mass and systolic performance in pediatric patients with chronic renal failure. Circulation 107:864–868PubMedCrossRef
14.
Park M, Shlipak MG, Katz R, Agarwal S, Ix JH, Hsu CY, Peralta CA (2012) Subclinical cardiac abnormalities and kidney function decline: the multi-ethnic study of atherosclerosis. Clin J Am Soc Nephrol 7:1137–1144PubMedPubMedCentralCrossRef
15.
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 119:2545–2552PubMedPubMedCentralCrossRef
16.
Mehta R, Cai X, Lee J, Scialla JJ, Bansal N, Sondheimer JH, Chen J, Hamm LL, Ricardo AC, Navaneethan SD, Deo R, Rahman M, Feldman HI, Go AS, Isakova T, Wolf M, Chronic Renal Insufficiency Cohort Study I (2016) Association of fibroblast growth factor 23 with atrial fibrillation in chronic kidney disease, from the Chronic Renal Insufficiency Cohort Study. JAMA Cardiol 1:548–556PubMedPubMedCentralCrossRef
17.
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 359:584–592PubMedPubMedCentralCrossRef
18.
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 121:4393–4408PubMedPubMedCentralCrossRef
19.
Fliser D, Wiecek A, Suleymanlar G, Ortiz A, Massy Z, Lindholm B, Martinez-Castelao A, Agarwal R, Jager KJ, Dekker FW, Blankestijn PJ, Goldsmith D, Covic A, London G, Zoccali C, for ER, Dialysis CAMwgotERA-E, Transplant A (2011) The dysfunctional endothelium in CKD and in cardiovascular disease: mapping the origin(s) of cardiovascular problems in CKD and of kidney disease in cardiovascular conditions for a research agenda. Kidney Int Suppl 1:6–9CrossRef
20.
Quek KJ, Boyd R, Ameer OZ, Zangerl B, Butlin M, Murphy TV, Avolio AP, Phillips JK (2016) Progressive vascular remodelling, endothelial dysfunction and stiffness in mesenteric resistance arteries in a rodent model of chronic kidney disease. Vasc Pharmacol 81:42–52CrossRef
21.
Shukla V, Dey R, Chandra A, Karoli R, Khanduri S (2015) Endothelial dysfunction by flow-mediated vasodilatation in chronic kidney disease. J Assoc Physicians India 63:30–33PubMed
22.
Burkhardt D, Bartosova M, Schaefer B, Grabe N, Lahrmann B, Nasser H, Freise C, Schneider A, Lingnau A, Degenhardt P, Ranchin B, Sallay P, Cerkauskiene R, Malina M, Ariceta G, Schmitt CP, Querfeld U (2016) Reduced microvascular density in omental biopsies of children with chronic kidney disease. PLoS One 11:e0166050PubMedPubMedCentralCrossRef
23.
Stevens KK, Denby L, Patel RK, Mark PB, Kettlewell S, Smith GL, Clancy MJ, Delles C, Jardine AG (2016) Deleterious effects of phosphate on vascular and endothelial function via disruption to the nitric oxide pathway. Nephrol Dial Transplant. https://​doi.​org/​10.​1093/​ndt/​gfw252
24.
El-Sadek AE, Behery EG, Azab AA, Kamal NM, Salama MA, Abdulghany WE, Abdallah EA (2016) Arginine dimethylation products in pediatric patients with chronic kidney disease. Ann Med Surg 9:22–27CrossRef
25.
Fujimi-Hayashida A, Ueda S, Yamagishi S, Kaida Y, Ando R, Nakayama Y, Fukami K, Okuda S (2011) Association of asymmetric dimethylarginine with severity of kidney injury and decline in kidney function in IgA nephropathy. Am J Nephrol 33:1–6PubMedCrossRef
26.
Von Haehling S, Bode-Boger SM, Martens-Lobenhoffer J, Rauchhaus M, Schefold JC, Genth-Zotz S, Karhausen T, Cicoira M, Anker SD, Doehner W (2010) Elevated levels of asymmetric dimethylarginine in chronic heart failure: a pathophysiologic link between oxygen radical load and impaired vasodilator capacity and the therapeutic effect of allopurinol. Clin Pharmacol Ther 88:506–512CrossRef
27.
Kuwahata S, Hamasaki S, Ishida S, Kataoka T, Yoshikawa A, Orihara K, Ogawa M, Oketani N, Saihara K, Okui H, Shinsato T, Kubozono T, Ichiki H, Fujita S, Takumi T, Yoshino S, Nakazaki M, Miyata M, Tei C (2010) Effect of uric acid on coronary microvascular endothelial function in women: association with eGFR and ADMA. J Atheroscler Thromb 17:259–269PubMedCrossRef
28.
Lariviere R, Gauthier-Bastien A, Ung RV, St-Hilaire J, Mac-Way F, Richard DE, Agharazii M (2017) Endothelin type a receptor blockade reduces vascular calcification and inflammation in rats with chronic kidney disease. J Hypertens 35:376–384PubMedCrossRef
29.
Garcia-Jerez A, Luengo A, Carracedo J, Ramirez-Chamond R, Rodriguez-Puyol D, Rodriguez-Puyol M, Calleros L (2015) Effect of uraemia on endothelial cell damage is mediated by the integrin linked kinase pathway. J Physiol 593:601–618 discussion 618PubMedCrossRef
30.
Richter B, Haller J, Haffner D, Leifheit-Nestler M (2016) Klotho modulates FGF23-mediated NO synthesis and oxidative stress in human coronary artery endothelial cells. Pflugers Arch 468:1621–1635PubMedCrossRef
31.
Damjanovic T, Djuric S, Schlieper G, Markovic N, Dimkovic S, Radojicic Z, Kruger T, Floege J, Dimkovic N (2009) Clinical features of hemodialysis patients with intimal versus medial vascular calcifications. J Nephrol 22:358–366PubMed
32.
Milliner DS, Zinsmeister AR, Lieberman E, Landing B (1990) Soft tissue calcification in pediatric patients with end-stage renal disease. Kidney Int 38:931–936PubMedCrossRef
33.
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 342:1478–1483PubMedCrossRef
34.
Oh J, Wunsch R, Turzer M, Bahner M, Raggi P, Querfeld U, Mehls O, Schaefer F (2002) Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation 106:100–105PubMedCrossRef
35.
Ishitani MB, Milliner DS, Kim DY, Bohorquez HE, Heimbach JK, Sheedy PF, Morgenstern BZ, Gloor JM, Murphy JG, McBane RD, Bielak LF, Peyser PA, Stegall MD (2005) Early subclinical coronary artery calcification in young adults who were pediatric kidney transplant recipients. Am J Transplant 5:1689–1693PubMedCrossRef
36.
Di Lullo L, Floccari F, Santoboni A, Barbera V, Rivera RF, Granata A, Morrone L, Russo D (2013) Progression of cardiac valve calcification and decline of renal function in CKD patients. J Nephrol 26:739–744PubMedCrossRef
37.
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 39:695–701PubMedCrossRef
38.
Okuno S, Ishimura E, Kitatani K, Fujino Y, Kohno K, Maeno Y, Maekawa K, Yamakawa T, Imanishi Y, Inaba M, Nishizawa Y (2007) Presence of abdominal aortic calcification is significantly associated with all-cause and cardiovascular mortality in maintenance hemodialysis patients. Am J Kidney Dis 49:417–425PubMedCrossRef
39.
Moe SM, Duan D, Doehle BP, O'Neill KD, Chen NX (2003) Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels. Kidney Int 63:1003–1011PubMedCrossRef
40.
Moe SM, O'Neill KD, Duan D, Ahmed S, Chen NX, Leapman SB, Fineberg N, Kopecky K (2002) Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. Kidney Int 61:638–647PubMedCrossRef
41.
Shroff RC, McNair R, Skepper JN, Figg N, Schurgers LJ, Deanfield J, Rees L, Shanahan CM (2010) Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification. J Am Soc Nephrol 21:103–112PubMedPubMedCentralCrossRef
42.
Murshed M, Harmey D, Millan JL, McKee MD, Karsenty G (2005) Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone. Genes Dev 19:1093–1104PubMedPubMedCentralCrossRef
43.
Bae E, Cha RH, Kim YC, An JN, Kim DK, Yoo KD, Lee SM, Kim MH, Park JT, Kang SW, Park JY, Lim CS, Kim YS, Yang SH, Lee JP (2017) Circulating TNF receptors predict cardiovascular disease in patients with chronic kidney disease. Medicine 96:e6666PubMedPubMedCentralCrossRef
44.
Ahmed S, O'Neill KD, Hood AF, Evan AP, Moe SM (2001) Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells. Am J Kidney Dis 37:1267–1276PubMedCrossRef
45.
Neven E, Dauwe S, De Broe ME, D'Haese PC, Persy V (2007) Endochondral bone formation is involved in media calcification in rats and in men. Kidney Int 72:574–581PubMedCrossRef
46.
Shao JS, Cai J, Towler DA (2006) Molecular mechanisms of vascular calcification: lessons learned from the aorta. Arterioscler Thromb Vasc Biol 26:1423–1430PubMedCrossRef
47.
Steitz SA, Speer MY, Curinga G, Yang HY, Haynes P, Aebersold R, Schinke T, Karsenty G, Giachelli CM (2001) Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res 89:1147–1154PubMedCrossRef
48.
Hanley KP, Oakley F, Sugden S, Wilson DI, Mann DA, Hanley NA (2008) Ectopic SOX9 mediates extracellular matrix deposition characteristic of organ fibrosis. J Biol Chem 283:14063–14071PubMedCrossRef
49.
Simionescu A, Philips K, Vyavahare N (2005) Elastin-derived peptides and TGF-beta1 induce osteogenic responses in smooth muscle cells. Biochem Biophys Res Commun 334:524–532PubMedCrossRef
50.
Simionescu A, Simionescu DT, Vyavahare NR (2007) Osteogenic responses in fibroblasts activated by elastin degradation products and transforming growth factor-beta1: role of myofibroblasts in vascular calcification. Am J Pathol 171:116–123PubMedPubMedCentralCrossRef
51.
Schulick AH, Taylor AJ, Zuo W, Qiu CB, Dong G, Woodward RN, Agah R, Roberts AB, Virmani R, Dichek DA (1998) Overexpression of transforming growth factor beta1 in arterial endothelium causes hyperplasia, apoptosis, and cartilaginous metaplasia. Proc Natl Acad Sci U S A 95:6983–6988PubMedPubMedCentralCrossRef
52.
Gross ML, Meyer HP, Ziebart H, Rieger P, Wenzel U, Amann K, Berger I, Adamczak M, Schirmacher P, Ritz E (2007) Calcification of coronary intima and media: immunohistochemistry, backscatter imaging, and x-ray analysis in renal and nonrenal patients. Clin J Am Soc Nephrol 2:121–134PubMedCrossRef
53.
54.
Dao HH, Essalihi R, Bouvet C, Moreau P (2005) Evolution and modulation of age-related medial elastocalcinosis: impact on large artery stiffness and isolated systolic hypertension. Cardiovasc Res 66:307–317PubMedCrossRef
55.
Shanahan CM, Cary NR, Salisbury JR, Proudfoot D, Weissberg PL, Edmonds ME (1999) Medial localization of mineralization-regulating proteins in association with Monckeberg's sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation 100:2168–2176PubMedCrossRef
56.
Lomashvili KA, Narisawa S, Millan JL, O'Neill WC (2014) Vascular calcification is dependent on plasma levels of pyrophosphate. Kidney Int 85:1351–1356PubMedPubMedCentralCrossRef
57.
Li X, Yang HY, Giachelli CM (2006) Role of the sodium-dependent phosphate cotransporter, Pit-1, in vascular smooth muscle cell calcification. Circ Res 98:905–912PubMedCrossRef
58.
Mizobuchi M, Ogata H, Hatamura I, Koiwa F, Saji F, Shiizaki K, Negi S, Kinugasa E, Ooshima A, Koshikawa S, Akizawa T (2006) Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism. Nephrol Dial Transplant 21:911–916PubMedCrossRef
59.
Thamratnopkoon S, Susantitaphong P, Tumkosit M, Katavetin P, Tiranathanagul K, Praditpornsilpa K, Eiam-Ong S (2017) Correlations of plasma desphosphorylated uncarboxylated matrix Gla protein with vascular calcification and vascular stiffness in chronic kidney disease. Nephron 135:167–172PubMedCrossRef
60.
Nigwekar SU, Bloch DB, Nazarian RM, Vermeer C, Booth SL, Xu D, Thadhani RI, Malhotra R (2017) Vitamin K-dependent carboxylation of matrix Gla protein influences the risk of calciphylaxis. J Am Soc Nephrol 28:1717–1722PubMedPubMedCentralCrossRef
61.
62.
Zhu D, Mackenzie NC, Shanahan CM, Shroff RC, Farquharson C, MacRae VE (2015) BMP-9 regulates the osteoblastic differentiation and calcification of vascular smooth muscle cells through an ALK1 mediated pathway. J Cell Mol Med 19:165–174PubMedCrossRef
63.
Fang Y, Ginsberg C, Seifert M, Agapova O, Sugatani T, Register TC, Freedman BI, Monier-Faugere MC, Malluche H, Hruska KA (2014) CKD-induced wingless/integration1 inhibitors and phosphorus cause the CKD-mineral and bone disorder. J Am Soc Nephrol 25:1760–1773PubMedPubMedCentralCrossRef
64.
Russo D, Palmiero G, De Blasio AP, Balletta MM, Andreucci VE (2004) Coronary artery calcification in patients with CRF not undergoing dialysis. Am J Kidney Dis 44:1024–1030PubMedCrossRef
65.
Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS (1998) Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12:1260–1268PubMedPubMedCentralCrossRef
66.
Van Campenhout A, Golledge J (2009) Osteoprotegerin, vascular calcification and atherosclerosis. Atherosclerosis 204:321–329PubMedCrossRef
67.
Smith ER, Ford ML, Tomlinson LA, Rajkumar C, McMahon LP, Holt SG (2012) Phosphorylated fetuin-A-containing calciprotein particles are associated with aortic stiffness and a procalcific milieu in patients with pre-dialysis CKD. Nephrol Dial Transplant 27:1957–1966PubMedCrossRef
68.
Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK (2001) Association of elevated serum PO(4), ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 12:2131–2138PubMedCrossRef
69.
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 24:948–955PubMedCrossRef
70.
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 26:945–951PubMedCrossRef
71.
Van Venrooij NA, Pereira RC, Tintut Y, Fishbein MC, Tumber N, Demer LL, Salusky IB, Wesseling-Perry K (2014) FGF23 protein expression in coronary arteries is associated with impaired kidney function. Nephrol Dial Transplant 29:1525–1532
72.
Scialla JJ, Lau WL, Reilly MP, Isakova T, Yang HY, Crouthamel MH, Chavkin NW, Rahman M, Wahl P, Amaral AP, Hamano T, Master SR, Nessel L, Chai B, Xie D, Kallem RR, Chen J, Lash JP, Kusek JW, Budoff MJ, Giachelli CM, Wolf M (2013) Fibroblast growth factor 23 is not associated with and does not induce arterial calcification. Kidney Int 83:1159–1168PubMedPubMedCentralCrossRef
73.
Mattinzoli D, Rastaldi MP, Ikehata M, Armelloni S, Pignatari C, Giardino LA, Li M, Alfieri CM, Regalia A, Riccardi D, Messa P (2016) FGF23-regulated production of Fetuin-A (AHSG) in osteocytes. Bone 83:35–47PubMedCrossRef
74.
Hu MC, Shi M, Zhang J, Quinones H, Griffith C, Kuro-o M, Moe OW (2011) Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol 22:124–136PubMedPubMedCentralCrossRef
75.
Matteucci MC, Chinali M, Rinelli G, Wuhl E, Zurowska A, Charbit M, Pongiglione G, Schaefer F, Group ET (2013) Change in cardiac geometry and function in CKD children during strict BP control: a randomized study. Clin J Am Soc Nephrol 8:203–210PubMedCrossRef
76.
Nursalim A, Siregar P, Widyahening IS (2013) Effect of folic acid, vitamin B6 and vitamin B12 supplementation on mortality and cardiovascular complication among patients with chronic kidney disease: an evidence-based case report. Acta Med Indones 45:150–156PubMed
77.
Dad T, Tighiouart H, Joseph A, Bostom A, Carpenter M, Hunsicker L, Kusek JW, Pfeffer M, Levey AS, Weiner DE (2016) Aspirin use and incident cardiovascular disease, kidney failure, and death in stable kidney transplant recipients: a post hoc analysis of the folic acid for vascular outcome reduction in transplantation (FAVORIT) trial. Am J Kidney Dis 68:277–286PubMedPubMedCentralCrossRef
78.
Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, Knecht A, Weissgarten Y, Brunner D, Fainaru M, Green MS (2000) Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet 356:1213–1218PubMedCrossRef
79.
Nataatmadja M, Cho Y, Fahim M, Johnson DW (2016) Recent clinical trials of pharmacologic cardiovascular interventions in patients with chronic kidney disease: an update. Rev Recent Clin Trials 11:12–32PubMedCrossRef
80.
Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG, Canadian Critical Care Trials Group (2013) A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med 368:1489–1497PubMedCrossRef
81.
Tonelli M, Keech A, Shepherd J, Sacks F, Tonkin A, Packard C, Pfeffer M, Simes J, Isles C, Furberg C, West M, Craven T, Curhan G (2005) Effect of pravastatin in people with diabetes and chronic kidney disease. J Am Soc Nephrol 16:3748–3754PubMedCrossRef
82.
Jun M, Zhu B, Tonelli M, Jardine MJ, Patel A, Neal B, Liyanage T, Keech A, Cass A, Perkovic V (2012) Effects of fibrates in kidney disease: a systematic review and meta-analysis. J Am Coll Cardiol 60:2061–2071PubMedCrossRef
83.
Hill KM, Martin BR, Wastney ME, McCabe GP, Moe SM, Weaver CM, Peacock M (2013) Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease. Kidney Int 83:959–966PubMedCrossRef
84.
Block GA, Wheeler DC, Persky MS, Kestenbaum B, Ketteler M, Spiegel DM, Allison MA, Asplin J, Smits G, Hoofnagle AN, Kooienga L, Thadhani R, Mannstadt M, Wolf M, Chertow GM (2012) Effects of phosphate binders in moderate CKD. J Am Soc Nephrol 23:1407–1405PubMedPubMedCentralCrossRef
85.
Slatopolsky E, Liapis H, Finch J (2005) Progressive accumulation of lanthanum in the liver of normal and uremic rats. Kidney Int 68:2809–2813PubMedCrossRef
86.
Spasovski GB, Sikole A, Gelev S, Masin-Spasovska J, Freemont T, Webster I, Gill M, Jones C, De Broe ME, D'Haese PC (2006) Evolution of bone and plasma concentration of lanthanum in dialysis patients before, during 1 year of treatment with lanthanum carbonate and after 2 years of follow-up. Nephrol Dial Transplant 21:2217–2224PubMedCrossRef
87.
Jamal SA, Vandermeer B, Raggi P, Mendelssohn DC, Chatterley T, Dorgan M, Lok CE, Fitchett D, Tsuyuki RT (2013) Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis. Lancet 382:1268–1277PubMedCrossRef
88.
Oliveira RB, Cancela AL, Graciolli FG, dos Reis LM, Draibe SA, Cuppari L, Carvalho AB, Jorgetti V, Canziani ME, Moyses RM (2010) Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol 5:286–291PubMedPubMedCentralCrossRef
89.
Isakova T, Gutierrez OM, Smith K, Epstein M, Keating LK, Juppner H, Wolf M (2011) Pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease. Nephrol Dial Transplant 26:584–591PubMedCrossRef
90.
Yokoyama K, Hirakata H, Akiba T, Fukagawa M, Nakayama M, Sawada K, Kumagai Y, Block GA (2014) Ferric citrate hydrate for the treatment of hyperphosphatemia in nondialysis-dependent CKD. Clin J Am Soc Nephrol 9:543–552PubMedPubMedCentralCrossRef
91.
Farrow EG, Yu X, Summers LJ, Davis SI, Fleet JC, Allen MR, Robling AG, Stayrook KR, Jideonwo V, Magers MJ, Garringer HJ, Vidal R, Chan RJ, Goodwin CB, Hui SL, Peacock M, White KE (2011) Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice. Proc Natl Acad Sci U S A 108:E1146–E1155PubMedPubMedCentralCrossRef
92.
Shroff R, Wan M, Gullett A, Ledermann S, Shute R, Knott C, Wells D, Aitkenhead H, Manickavasagar B, van't Hoff W, Rees L (2012) Ergocalciferol supplementation in children with CKD delays the onset of secondary hyperparathyroidism: a randomized trial. Clin J Am Soc Nephrol 7:216–223PubMedCrossRef
93.
94.
Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernan MA, Camargo CA Jr, Thadhani R (2005) Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol 16:1115–1125PubMedCrossRef
95.
Kalantar-Zadeh K, Kuwae N, Regidor DL, Kovesdy CP, Kilpatrick RD, Shinaberger CS, McAllister CJ, Budoff MJ, Salusky IB, Kopple JD (2006) Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 70:771–780PubMedCrossRef
96.
Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R (2003) Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 349:446–456PubMedCrossRef
97.
Wolf M, Betancourt J, Chang Y, Shah A, Teng M, Tamez H, Gutierrez O, Camargo CA Jr, Melamed M, Norris K, Stampfer MJ, Powe NR, Thadhani R (2008) Impact of activated vitamin D and race on survival among hemodialysis patients. J Am Soc Nephrol 19:1379–1388PubMedPubMedCentralCrossRef
98.
Tamez H, Zoccali C, Packham D, Wenger J, Bhan I, Appelbaum E, Pritchett Y, Chang Y, Agarwal R, Wanner C, Lloyd-Jones D, Cannata J, Thompson BT, Andress D, Zhang W, Singh B, Zehnder D, Pachika A, Manning WJ, Shah A, Solomon SD, Thadhani R (2012) Vitamin D reduces left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease. Am Heart J 164:902–909.e2PubMedCrossRef
99.
Alam MU, Kirton JP, Wilkinson FL, Towers E, Sinha S, Rouhi M, Vizard TN, Sage AP, Martin D, Ward DT, Alexander MY, Riccardi D, Canfield AE (2009) Calcification is associated with loss of functional calcium-sensing receptor in vascular smooth muscle cells. Cardiovasc Res 81:260–268PubMedCrossRef
100.
Raggi P, Chertow GM, Torres PU, Csiky B, Naso A, Nossuli K, Moustafa M, Goodman WG, Lopez N, Downey G, Dehmel B, Floege J (2011) The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant 26:1327–1339PubMedCrossRef
101.
Cunningham J, Danese M, Olson K, Klassen P, Chertow GM (2005) Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. Kidney Int 68:1793–1800PubMedCrossRef
102.
Kim HJ, Kim H, Shin N, Na KY, Kim YL, Kim D, Chang JH, Song YR, Hwang YH, Kim YS, Ahn C, Lee J, Oh KH, Representing the Cinacalcet stUdy for Peritoneal Dialysis Patients In Double Arm on the Lowing Effect Of iPTH Level (CUPID) Study Group (2013) Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: a randomized controlled study. BMC Nephrol 14:112PubMedPubMedCentralCrossRef
103.
Moe SM, Chertow GM, Parfrey PS, Kubo Y, Block GA, Correa-Rotter R, Drueke TB, Herzog CA, London GM, Mahaffey KW, Wheeler DC, Stolina M, Dehmel B, Goodman WG, Floege J, Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators (2015) Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis: the evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial. Circulation 132:27–39PubMedCrossRef
104.
Chertow GM, Block GA, Correa-Rotter R, Drueke TB, Floege J, Goodman WG, Herzog CA, Kubo Y, London GM, Mahaffey KW, Mix TC, Moe SM, Trotman ML, Wheeler DC, Parfrey PS (2012) Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med 367:2482–2494PubMedCrossRef
105.
Litwin M, Wuhl E, Jourdan C, Trelewicz J, Niemirska A, Fahr K, Jobs K, Grenda R, Wawer ZT, Rajszys P, Troger J, Mehls O, Schaefer F (2005) Altered morphologic properties of large arteries in children with chronic renal failure and after renal transplantation. J Am Soc Nephrol 16:1494–1500PubMedCrossRef
106.
Mitsnefes MM, Kimball TR, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2004) Abnormal carotid artery structure and function in children and adolescents with successful renal transplantation. Circulation 110:97–101PubMedCrossRef
107.
Balzano R, Lindblad YT, Vavilis G, Jogestrand T, Berg UB, Krmar RT (2011) Use of annual ABPM, and repeated carotid scan and echocardiography to monitor cardiovascular health over nine yr in pediatric and young adult renal transplant recipients. Pediatr Transplant 15:635–641PubMedCrossRef
108.
Kmar RT, Balzano R, Jogestrand T, Cedazo-Minguez A, Englund MD, Breg UB (2008) Prospective analysis of carotid arterial wall structure in pediatric renal transplants with ambulatory normotensin and in treated hypertensive receipients. Pediatr Transplant 12:410–419
Metadata
Title
Pathophysiology and treatment of cardiovascular disease in pediatric chronic kidney disease
Authors
Nadine Khouzam
Katherine Wesseling-Perry
Publication date
01-01-2019
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 1/2019
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-017-3798-x

Other articles of this Issue 1/2019

Pediatric Nephrology 1/2019 Go to the issue

Letter to the Editor

Total body water measurement in childhood

Educational Review

Assessment of dialysis adequacy: beyond urea kinetic measurements

Brief Report

B cell phenotype in pediatric idiopathic nephrotic syndrome

Original Article

Cinacalcet as rescue therapy for refractory hyperparathyroidism in young children with advanced chronic kidney disease

Original Article

Renal function and blood pressure are altered in adolescents born preterm

Original Article

An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis