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Current Hypertension Reviews


ISSN (Print): 1573-4021
ISSN (Online): 1875-6506

Review Article

Secondary Hypertension in Children and Adolescents: Novel Insights

Author(s): Katerina Chrysaidou, Athanasia Chainoglou, Vasiliki Karava, John Dotis, Nikoleta Printza and Stella Stabouli*

Volume 16 , Issue 1 , 2020

Page: [37 - 44] Pages: 8

DOI: 10.2174/1573402115666190416152820


Hypertension is a significant risk factor for cardiovascular morbidity and mortality, not only in adults, but in youths also, as it is associated with long-term negative health effects. The predominant type of hypertension in children is the secondary hypertension, with the chronic kidney disease being the most common cause, however, nowadays, there is a rising incidence of primary hypertension due to the rising incidence of obesity in children. Although office blood pressure has guided patient management for many years, ambulatory blood pressure monitoring provides useful information, facilitates the diagnosis and management of hypertension in children and adolescents, by monitoring treatment and evaluation for secondary causes or specific phenotypes of hypertension. In the field of secondary hypertension, there are numerous studies, which have reported a strong association between different determinants of 24-hour blood pressure profile and the underlying cause. In addition, in children with secondary hypertension, ambulatory blood pressure monitoring parameters offer the unique advantage to identify pediatric low- and high-risk children for target organ damage. Novel insights in the pathogenesis of hypertension, including the role of perinatal factors or new cardiovascular biomarkers, such as fibroblast growth factor 23, need to be further evaluated in the near future.

Keywords: Children, hypertension, ambulatory blood pressure, chronic kidney disease, prematurity, diagnosis.

Graphical Abstract
Juhola J, Magnussen CG, Berenson GS, et al. Combined effects of child and adult elevated blood pressure on subclinical atherosclerosis: The International Childhood Cardiovascular Cohort Consortium. Circulation 2013; 128(3): 217-24.
Chen X, Wang Y. Tracking of blood pressure from childhood to adulthood: A systematic review and meta-regression analysis. Circulation 2008; 117(25): 3171-80.
Flynn JT, Kaelber DC, Baker-Smith CM, et al. Subcommittee on screening and management of high blood pressure in children. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 2017; 140(3)e20171904
Rao G. Diagnosis, epidemiology, and management of hypertension in children. Pediatrics 2016; 138(2 : pii: )e20153616
Lurbe E, Agabiti-Rosei E, Cruickshank JK, et al. 2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents. J Hypertens 2016; 34(10): 1887-920.
Genovesi S, Giussani M, Pieruzzi F, et al. Results of blood pressure screening in a population of school-aged children in the province of Milan: Role of overweight. J Hypertens 2005; 23(3): 493-7.
Falkner B. Recent clinical and translational advances in pediatric hypertension. Hypertension (Dallas, Tex : 1979) 2015; 65(5): 926-31.
Flynn JT, Mitsnefes M, Pierce C, et al. Blood pressure in children with chronic kidney disease: A report from the Chronic Kidney Disease in Children study. Hypertension (Dallas, Tex : 1979) 2008; 52(4): 631-7.
Wyszynska T, Cichocka E, Wieteska-Klimczak A, Jobs K, Januszewicz P. A single pediatric center experience with 1025 children with hypertension. Acta Paediatr 1992; 81(3): 244-6.
Arar MY, Hogg RJ, Arant BS Jr, Seikaly MG. Etiology of sustained hypertension in children in the southwestern United States. Pediatr Nephrol 1994; 8(2): 186-9.
Gomes RS, Quirino IG, Pereira RM, et al. Primary versus secondary hypertension in children followed up at an outpatient tertiary unit. Pediatr Nephrol 2011; 26(3): 441-7.
Viera AJ, Neutze DM. Diagnosis of secondary hypertension: An age-based approach. Am Fam Physician 2010; 82(12): 1471-8.
Dillon MJ. Renovascular hypertension. J Hum Hypertens 1994; 8(5): 367-9.
Tullus K, Brennan E, Hamilton G, et al. Renovascular hypertension in children. Lancet 2008; 371(9622): 1453-63.
Ellis D, Shapiro R, Scantlebury VP, Simmons R, Towbin R. Evaluation and management of bilateral renal artery stenosis in children: A case series and review. Pediatr Nephrol 1995; 9(3): 259-67.
Tullus K. Renovascular hypertension--is it fibromuscular dysplasia or Takayasu arteritis. Pediatr Nephrol 2013; 28(2): 191-6.
Lee Y, Lim YS, Lee ST, Cho H. Pediatric renovascular hypertension: Treatment outcome according to underlying disease. Pediatr Int 2018; 60(3): 264-9.
Kapur G, Baracco R. Evaluation of hypertension in children. Curr Hypertens Rep 2013; 15(5): 433-43.
Croix B, Feig DI. Childhood hypertension is not a silent disease. Pediatr Nephrol 2006; 21(4): 527-32.
Kapur G, Ahmed M, Pan C, Mitsnefes M, Chiang M, Mattoo TK. Secondary hypertension in overweight and stage 1 hypertensive children: A Midwest Pediatric Nephrology Consortium report. J Clin Hypertens (Greenwich) 2010; 12(1): 34-9.
Falkner B, Gidding SS, Portman R, Rosner B. Blood pressure variability and classification of prehypertension and hypertension in adolescence. Pediatrics 2008; 122(2): 238-42.
Flynn JT, Daniels SR, Hayman LL, et al. Update: Ambulatory blood pressure monitoring in children and adolescents: A scientific statement from the American Heart Association. Hypertension (Dallas, Tex : 1979) 2014; 63(5): 1116-35.
Flynn JT, Urbina EM. Pediatric ambulatory blood pressure monitoring: Indications and interpretations. J Clin Hypertens (Greenwich) 2012; 14(6): 372-82.
Flynn JT. Differentiation between primary and secondary hypertension in children using ambulatory blood pressure monitoring. Pediatrics 2002; 110(1 Pt 1): 89-93.
Drawz PE, Abdalla M, Rahman M. Blood pressure measurement: Clinic, home, ambulatory, and beyond. Am J Kidney Dis 2012; 60(3): 449-62.
Lee SH, Kim JH, Kang MJ, Lee YA, Won Yang S, Shin CH. Implications of nocturnal hypertension in children and adolescents with type 1 diabetes. Diabetes Care 2011; 34(10): 2180-5.
Lurbe E, Redon J, Kesani A, et al. Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med 2002; 347(11): 797-805.
Samuels J, Ng D, Flynn JT, et al. Ambulatory blood pressure patterns in children with chronic kidney disease. Hypertension (Dallas, Tex: 1979) 2012; 60(1): 43-50.
McGlothan KR, Wyatt RJ, Ault BH, et al. Predominance of nocturnal hypertension in pediatric renal allograft recipients. Pediatr Transplant 2006; 10(5): 558-64.
Stabouli S, Kotsis V, Toumanidis S, Papamichael C, Constantopoulos A, Zakopoulos N. White-coat and masked hypertension in children: Association with target-organ damage. Pediatr Nephrol 2005; 20(8): 1151-5.
Stabouli S, Kotsis V, Zakopoulos N. Ambulatory blood pressure monitoring and target organ damage in pediatrics. J Hypertens 2007; 25(10): 1979-86.
Mitsnefes M, Flynn J, Cohn S, et al. Masked hypertension associates with left ventricular hypertrophy in children with CKD. J Am Soc Nephrol 2010; 21(1): 137-44.
Sulakova T, Janda J, Cerna J, et al. Arterial HTN in children with T1DM--frequent and not easy to diagnose. Pediatr Diabetes 2009; 10(7): 441-8.
Agarwal R, Andersen MJ. Prognostic importance of clinic and home blood pressure recordings in patients with chronic kidney disease. Kidney Int 2006; 69(2): 406-11.
Lurbe E, Torro I, Alvarez V, et al. Prevalence, persistence, and clinical significance of masked hypertension in youth. Hypertension (Dallas, Tex: 1979) 2005; 45(4): 493-8.
Di Salvo G, Castaldi B, Baldini L, et al. Masked hypertension in young patients after successful aortic coarctation repair: Impact on left ventricular geometry and function. J Hum Hypertens 2011; 25(12): 739-45.
Shatat IF, Flynn JT. Hypertension in children with chronic kidney disease. Adv Chronic Kidney Dis 2005; 12(4): 378-84.
Macumber I. Ambulatory blood pressure monitoring in children and adolescents: A review of recent literature and new guidelines. Curr Hypertens Rep 2017; 19(12): 96.
Flynn JT, Alderman MH. Characteristics of children with primary hypertension seen at a referral center. Pediatr Nephrol 2005; 20(7): 961-6.
Seeman T, Palyzova D, Dusek J, Janda J. Reduced nocturnal blood pressure dip and sustained nighttime hypertension are specific markers of secondary hypertension. J Pediatr 2005; 147(3): 366-71.
Chavers BM, Solid CA, Daniels FX, et al. Hypertension in pediatric long-term hemodialysis patients in the United States. Clin J Am Soc Nephrol 2009; 4(8): 1363-9.
Chaudhuri A, Sutherland SM, Begin B, et al. Role of twenty-four-hour ambulatory blood pressure monitoring in children on dialysis. Clin J Am Soc Nephrol 2011; 6(4): 870-6.
Bald M, Lettgen B, Wingen AM, Bonzel KE. 24-hour blood pressure monitoring in children and adolescents after recovery from hemolytic uremic syndrome. Clin Nephrol 1996; 46(1): 50-3.
Seeman T, John U, Blahova K, Vondrichova H, Janda J, Misselwitz J. Ambulatory blood pressure monitoring in children with unilateral multicystic dysplastic kidney. Eur J Pediatr 2001; 160(2): 78-83.
Seeman T, Dusek J, Vondrichova H, et al. Ambulatory blood pressure correlates with renal volume and number of renal cysts in children with autosomal dominant polycystic kidney disease. Blood Press Monit 2003; 8(3): 107-10.
Westland R, Schreuder MF, van der Lof DF, et al. Ambulatory blood pressure monitoring is recommended in the clinical management of children with a solitary functioning kidney. Pediatr Nephrol 2014; 29(11): 2205-11.
Lee MG, Kowalski R, Galati JC, et al. Twenty-four-hour ambulatory blood pressure monitoring detects a high prevalence of hypertension late after coarctation repair in patients with hypoplastic arches. J Thorac Cardiovasc Surg 2012; 144(5): 1110-6.
Lee MG, Allen SL, Kawasaki R, et al. High prevalence of hypertension and end-organ damage late after coarctation repair in normal arches. Ann Thorac Surg 2015; 100(2): 647-53.
O’Sullivan JJ, Derrick G, Darnell R. Prevalence of hypertension in children after early repair of coarctation of the aorta: A cohort study using casual and 24 hour blood pressure measurement. Heart 2002; 88(2): 163-6.
Brown ML, Burkhart HM, Connolly HM, et al. Coarctation of the aorta: Lifelong surveillance is mandatory following surgical repair. J Am Coll Cardiol 2013; 62(11): 1020-5.
Marcovecchio ML, Dalton RN, Schwarze CP, et al. Ambulatory blood pressure measurements are related to albumin excretion and are predictive for risk of microalbuminuria in young people with type 1 diabetes. Diabetologia 2009; 52(6): 1173-81.
ESCAPE Trial Group, Wühl E, Trivelli A, Picca S, et al. . Strict blood-pressure control and progression of renal failure in children. N Engl J Med 2009; 361(17): 1639-50.
Seeman T, Dostalek L, Gilik J. Control of hypertension in treated children and its association with target organ damage. Am J Hypertens 2012; 25(3): 389-95.
Sieber US, von Vigier RO, Sforzini C, Fossali E, Edefonti A, Bianchetti MG. How good is blood pressure control among treated hypertensive children and adolescents? J Hypertens 2003; 21(3): 633-7.
Silverstein DM, Champoux E, Aviles DH, Vehaskari VM. Treatment of primary and secondary hypertension in children. Pediatr Nephrol 2006; 21(6): 820-7.
Svensson P, de Faire U, Sleight P, Yusuf S, Ostergren J. Comparative effects of ramipril on ambulatory and office blood pressures: A HOPE Substudy. Hypertension (Dallas, Tex: 1979) 2001; 38(6): E28-32.
Woroniecki RP, Flynn JT. How are hypertensive children evaluated and managed? A survey of North American pediatric nephrologists. Pediatr Nephrol 2005; 20(6): 791-7.
Zohdi V, Sutherland MR, Lim K, Gubhaju L, Zimanyi MA, Black MJ. Low birth weight due to intrauterine growth restriction and/or preterm birth: effects on nephron number and long-term renal health. Int J Nephrol 2012; 2012:136942
Luyckx VA, Bertram JF, Brenner BM, et al. Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease. Lancet 2013; 382(9888): 273-83.
Savant JD, Furth SL, Meyers KE. Arterial stiffness in children: Pediatric measurement and considerations. Pulse 2014; 2(1-4): 69-80.
Franco MCCD, Carneiro-Ramos MS, Sawaya AL, Barreto-Chaves ML, Sesso R. Circulating renin-angiotensin system and catecholamines in childhood: Is there a role for birthweight? Clin Sci (Lond) 2008; 114(5): 375-80.
Simonetti GD, Raio L, Surbek D, Nelle M, Frey FJ, Mohaupt MG. Salt sensitivity of children with low birth weight. Hypertension 2008; 52(4): 625-30.
Poplawska K, Dudek K, Koziarz M, et al. Prematurity-related hypertension in children and adolescents. Int J Pediatr 2012; 2012:537936
Sipola-Leppänen M, Karvonen R, Tikanmäki M, et al. Ambulatory blood pressure and its variability in adults born preterm. Hypertension 2015; 65(3): 615-21.
Mu M, Wang SF, Sheng J, et al. Birth weight and subsequent blood pressure: A meta-analysis. Arch Cardiovasc Dis 2012; 105(2): 99-113.
de Jong F, Monuteaux MC, van Elburg RM, Gillman MW, Belfort MB. Systematic review and meta-analysis of preterm birth and later systolic blood pressure. Hypertension 2012; 59(2): 226-34.
Huxley RR, Shiell AW, Law CM. The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: A systematic review of the literature. J Hypertens 2000; 18(7): 815-31.
Zohdi V, Sutherland MR, Lim K, Gubhaju L, Zimanyi MA, Black MJ. Low birth weight due to intrauterine growth restriction and/or preterm birth: Effects on nephron number and long-term renal health. Int J Nephrol 2012; 2012:136942
Komaba H, Fukagawa M. FGF23-parathyroid interaction: implications in chronic kidney disease. Kidney Int 2010; 77(4): 292-8.
Nitta K. Fibroblast growth factor 23 and cardiovascular disease in patients with chronic kidney disease. Renal Replacement Therapy 2018; 4(1): 31.
Scialla JJ, Xie H, Rahman M, et al. Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol 2014; 25(2): 349-60.
Xue C, Yang B, Zhou C, et al. Fibroblast growth factor 23 predicts all-cause mortality in a dose-response fashion in pre-dialysis patients with chronic kidney disease. Am J Nephrol 2017; 45(2): 149-59.
Fyfe-Johnson AL, Alonso A, Selvin E, et al. Serum fibroblast growth factor-23 and incident hypertension: The Atherosclerosis Risk in Communities (ARIC) Study. J Hypertens 2016; 34(7): 1266-72.
Zajac M, Rybi-Szuminska A, Wasilewska A. Urine fibroblast growth factor 23 levels in hypertensive children and adolescents. Croat Med J 2015; 56(4): 344-50.
Andrukhova O, Slavic S, Smorodchenko A, et al. FGF23 regulates renal sodium handling and blood pressure. EMBO Mol Med 2014; 6(6): 744-59.
Yamada S, Giachelli CM. Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho. Bone 2017; 100: 87-93.
Pi M, Ye R, Han X, et al. Cardiovascular interactions between fibroblast growth factor-23 and angiotensin II. Sci Rep 2018; 8(1): 12398.
de Borst MH, Vervloet MG, ter Wee PM, Navis G. Cross talk between the renin-angiotensin-aldosterone system and vitamin D-FGF-23-klotho in chronic kidney disease. J Am Soc Nephrol 2011; 22(9): 1603-9.
Leifheit-Nestler M, Grosse Siemer R, Flasbart K, et al. Induction of cardiac FGF23/FGFR4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease. Nephrol Dial Transplant 2016; 31(7): 1088-99.
Fukumoto S. Targeting fibroblast growth factor 23 signaling with antibodies and inhibitors, is there a rationale? Front Endocrinol (Lausanne) 2018; 9: 48.
Moe SM, Chertow GM, Parfrey PS, et al. Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis: The evaluation of cinacalcet hcl therapy to lower cardiovascular events (EVOLVE) trial. Circulation 2015; 132(1): 27-39.

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