Arrterial hypertension (HTN) is one of the most common sequelae of chronic kidney disease (CKD) in children. In children with chronic kidney disease (CKD) HTN is several times higher than in the general pediatric population. With progression of CKD, HTN increases, reaching 45-60% in dialysis patients. The regulation of hypertension in children is mandatory in the treatment of CKD due to the fact that hypertension is often goes unrecognized, insufficiently controlled and often masked. The etiology of hypertension is different depending on the age of diagnosis. In newborns and young children, hypertension occurs due to renovascular diseases such as renal venous thrombosis, renal artery stenosis and other renal parenchymal diseases. HTN is considered a marker for disease severity in CKD and is a risk factor for accelerated deterioration of kidney function as well as for cardiovascular disease. Activation of the renin–angiotensin–aldosterone system plays a pivotal role in renal hypertension. Оbesity and hyperuricemia are the risk factors for HTN in CKD in children and lead to the progression of CKD. HTN-induced target organ damage (TOD) manifests as microalbuminuria/proteinuria, retinopathy, increase in intima media thickness, atherosclerosis, reduced arterial compliance, cognitive impairment, and left ventricular hypertrophy (LVH). In adults and children with CKD, ABPM has been found to be superior than causal blood pressure to diagnose hypertension and to monitor adequacy of treatment. The main drug therapy used in children with HTN and CKD consists of ACE inhibitors. Strict BP control and limitation of proteinuria with ACE inhibitors and angiotensin receptor blockers (ARB) can slow the progression of CKD.
Arterial Hypertension in Children with Chronic Kidney Diseases, American Journal of Pediatrics. Special Issue: Chronic Kidney Disease in Children.
Vol. 6, No. 2,
2020, pp. 109-116.
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. 2008; 52 (4): 631–637. DOI: 0.1161/HYPERTENSIONAHA.108.
Tsygin AN, Arterial hypertension in children. Pediatric Nephrology. E. Leumann, A. N. Tsygin, A. A. Sarkissian (eds). Moscow: Litterra, 2010; 244–251
Ku. E, Kwok J. Definition of CKD. Adolescents with Chronic Kidney Disease. M. N. Haddad, E. Winniki, S. Nguyen (eds). Nature Switzerland AG 2019; 1-2.
Swinford RD, Portman RJ. Measurement and treatment of elevated blood pressure in the pediatric patient with chronic kidney disease. Adv Chronic Kidney Dis. 2004; 11 (2): 143–161. DOI: 10.1053/j.arrt.2004.02.001.
Avner ED et al eds. Chronic Kidney Disease. Pediatric Nephrology. 7th ed. Springer Reference, New York 2016; 2061-2064.
Massengill SF, Ferris M. Chronic kidney disease in children and adolescents. Pediatr Rev. 2014; 35 (1): 16–29. DOI: 10.1542/pir.35-1-16.
Halbach S, Flynn J. Treatment of hypertension in children with chronic kidney disease. Curr Hypertension Rep. 2015; 17 (1): 503. DOI: 10.1007/s11906-014-0503-.
Savenkova N. D. Renal Arterial Hypertension in children and adolescents: causes, classification, diagnosis. Ros Vestn Perinatol i Pediatr 2017; 62: (4): 43–48. DOI: 10.21508/1027–4065–2017–62–4–43–48.
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): 137–144. DOI: 10.1681/ASN.2009060609 ed.
Hadtstein C, Schaefer F. Hypertension in children with chronic kidney disease: pathophysiology and management. Pediatr Nephrol (Berlin, Germany) 2008; 23 (3): 363–371. DOI: 10.1007/s00467-007-0643-7.
Harambat J, van Stralen KJ, Kim JJ et al. Epidemiology of chronic kidney disease in children. Pediatr Nephrol 2012; 27: 363–373. DOI: 10.1007/s00467-011-1939-1.
Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015; 116 (6): 960–975. DOI: 10.1161/CIRCRESAHA.116.303587.
Wen Chen, Kirstie Ducharme-Smith, Laura Davis, Alvin Wun Fung Hui, Bradley Warady. Dietary Sources of Energy and Nutrient Intake among Children and Adolescents with CKD. Pediatr Nephrol. 2017 Jul; 32 (7): 1233–1241. DOI: 10.1007/s00467-017-3580-0.
Rees L, Mak RH. Nutrition and growth in children with chronic kidney disease. Nat Rev Nephrol. 2011; 7 (11): 615–623. DOI: 10.1038/nrneph.2011.137.
Rozanov V. B. Prognostic value of blood pressure in adolescence (22 year prospective observation). Rost Vestn Perinatol Pediat 2006; 5: 27-41.
Karimdzhanov IA, Israilova NA. Chronic kidney disease in children (literature review). Child health. 2017; 12 (7): 146-154 (in Russ)] DOI: 10.22141/2224-05184.108.40.2067.116190.
Wuhl E, Hadtstein C, Mehls O, Schaefer F, Escape Trial G. Home, clinic, and ambulatory blood pressure monitoring in children with chronic renal failure. Pediatr Res. 2004; 55 (3): 492–7. DOI.org/10.1203/01.PDR.0000106863.90996.76.
Mitsnefes M, Stablein D. Hypertension in pediatric patients on long-term dialysis: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Am J Kidney Dis. 2005; 45 (2): 309–15. DOI: 10.1053/j.ajkd.2004.11.006.
Dionne JM, Abitbol CL, Flynn JT. Hypertension in infancy: diagnosis, management and outcome. Pediatr Nephrol (Berlin, Germany) 2012; 27 (1): 17–32. DOI: 10.1007/s00467-010-1755-z.
Flynn JT. Neonatal hypertension: diagnosis and management. Pediatr Nephrol (Berlin, Germany) 2000; 14 (4): 332–341. DOI: 10.1007/s004670050771.
Flynn JT. Hypertension in the neonatal period. Curr Opin Pediatr. 2012; 24 (2): 197–204. DOI: 10.1097/MOP.0b013e32834f8329.
Tkaczyk M, Stanczyk M, Miklaszewska M, et al. What has changed in the prevalence of hypertension in dialyzed children during the last decade? Ren Fail. 2017; 39 (1): 283–289. DOI: 10.1080/0886022X.2016.1260033.
Samuels J, Ng D, Flynn JT, et al. Ambulatory blood pressure patterns in children with chronic kidney disease. Hypertension. 2012; 60 (1): 43–50. tDOI.org/10.1161/HYPERTENSIONAHA.111.189266.
Wong H, Mylrea K, Feber J, Drukker A, Filler G. Prevalence of complications in children with chronic kidney disease according to KDOQI. Kidney Int. 2006; 70 (3): 585–590. DOI: 10.1038/sj.ki.5001608.
Agarwal R, Flynn J, Pogue V, Rahman M, Reisin E, Weir MR. Assessment and management of hypertension in patients on dialysis. J Am Soc Nephrol. 2014; 25 (8): 1630–1646. DOI: 10.1681/ASN.2013060601.
Horowitz B, Miskulin D, Zager P. Epidemiology of hypertension in CKD. Adv Chronic Kidney Dis. 2015; 22 (2): 88–95. DOI: 10.1053/j.ackd.2014.09.004.
Klag MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med. 1996; 334 (1): 13–18. DOI: 10.1056/NEJM199601043340103.
Middleton RJ, Parfrey PS, Foley RN. Left ventricular hypertrophy in the renal patient. J Am Soc Nephrol. 2001; 12 (5): 1079–1084. PMID: 11316868.
Brass H, Ochs HG, Armbruster H, Heintz R. Plasma renin activity (PRA) and aldosterone (PA) in patients with chronic glomerulonephritis (GN) and hypertension. Clin Nephrol 1976; 5: 57–60. PMID: 943254.
Warren DJ, Ferris TF, Renin secretion in renal hypertension. Lancet.1970 1: 159–162. DOI: 10.1016/s0140-6736(70)90404-6.
Loghman-Adham M, Soto CE, Inagami T, Cassis L. The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am J Physiol Renal Physiol. 2004; 287: F775–F788. DOI: 10.1152/ajprenal.00370.2003.
Wolf G, Butzmann U, Wenzel UO. The renin-angiotensin system and progression of renal disease: from hemodynamics to cell biology. Nephron Physiol. 2003 93: P3–P13. DOI: 10.1159/000066656.
Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007; 116 (1): 85–97. DOI: 10.1161/CIRCULATIONAHA.106.678342.
Thomas P, Dasgupta I. The role of the kidney and the sympathetic nervous system in hypertension. Pediatr Nephrol (Berlin, Germany) 2015; 30 (4): 549–560. DOI: 10.1007/s00467-014-2789-4.
Reid IA. Role of nitric oxide in the regulation of renin and vasopressin secretion. Front Neuroendocrinol. 1994; 15 (4): 351–383. DOI: 10.1006/frne.1994.1014.
Urushihara M, Kagami S. Role of the intrarenal renin-angiotensin system in the progression of renal disease. Pediatr Nephrol (Berlin, Germany) 2016: 1–9. DOI: 10.1007/s00467-016-3449-7.
Joppich R, Weber P. Effects of ADH on the activity and function of the renin-angiotensin-aldosterone system in infants and in children. Eur J Pediatr. 1976; 122 (4): 303–308. https://doi.org/10.1007/BF00481512.
Noone D, Licht C. Chronic kidney disease: a new look at pathogenetic mechanisms and treatment options. Pediatr Nephrol (Berlin, Germany) 2014; 29 (5): 779–792. DOI: 10.1007/s00467-013-2436-5.
D’Amico G, Bazzi C. Pathophysiology of proteinuria. Kidney Int. 2003; 63 (3): 809–825. DOI: 10.1046/j.1523-1755.2003.00840.x.
Eddy AA. Progression in chronic kidney disease. Adv Chronic Kidney Dis. 2005; 12 (4): 353–365. DOI: 10.1053/j.ackd.2005.07.011.
Wong CS, Pierce CB, Cole SR, et al. Association of proteinuria with race, cause of chronic kidney disease, and glomerular filtration rate in the chronic kidney disease in children study. Clin J Am Soc Nephrol. 2009; 4 (4): 812–819. DOI: 10.2215/CJN.01780408.
Inker LA, Coresh J, Levey AS, Tonelli M, Muntner P. Estimated GFR, albuminuria, and complications of chronic kidney disease. J Am Soc Nephrol. 2011; 22 (12): 2322–2331. DOI: 10.1681/ASN.2010111181.
WHO Updated Factsheet 2016. Obesity and owerweight. http://www.who.int/mediacentre/factsheets/fs311/ru.
Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of obesity among adults and youth: United States, 2011–2014. NCHS Data Brief. 2015; (219): 1–8. http://www.cdc.gov/nchs/products/databriefs.htm.
Cattaneo A, Monasta L, Stamatakis E, et al. Overweight and obesity in infants and pre-school children in the European Union: a review of existing data. Obes Rev. 2010; 11 (5): 389–398. DOI: 10.1111/j.1467-789X.2009.00639.x.
Dzhumagaziev AA., Bezrukova DA., Bogdanyants MV et al. Obesity in Children in the Modern World: Realities and Possible Solutions. Current Pediatrics. 2016; 15 (3): 250-256. https://doi.org/10.15690/vsp.v15i3.1561.
Kovesdy CP, Furth S, Zoccali C. Obesity and kidney disease: hidden consequences of the epidemic. Rev Med Chil. 2017; 145 (3): 281–291. DOI: 10.4103/ijn.IJN_61_17.
Foster MC, Hwang SJ, Larson MG, et al. Overweight, obesity, and the development of stage 3 CKD: the Framingham Heart Study. Am J Kidney Dis. 2008; 52 (1): 39–48. DOI: 10.1053/j.ajkd.2008.03.003.
Kanasaki K, Kitada M, Kanasaki M, Koya D. The biological consequence of obesity on the kidney. Nephrol Dial Transplant. 2013; 28 (Suppl 4): iv1–iv7. https://doi.org/10.1093/ndt/gft098.
Savino A, Pelliccia P, Chiarelli F, Mohn A. Obesity-related renal injury in childhood. Horm Res Paediatr. 2010; 73 (5): 303–311. DOI: 10.1159/000308161.
Tsuboi N, Utsunomiya Y, Hosoya T. Obesity-related glomerulopathy and the nephron complement. Nephrol Dial Transplant. 2013; 28 (Suppl 4): iv108–iv113. DOI: 10.1093/ndt/gft258.
Ruster C, Wolf G. The role of the renin-angiotensin-aldosterone system in obesity-related renal diseases. Semin Nephrol. 2013; 33 (1): 44–53. DOI: 10.1016/j.semnephrol.2012.12.002.
Litwin M, Niemirska A. Metabolic syndrome in children with chronic kidney disease and after renal transplantation. Pediatr Nephrol (Berlin, Germany) 2014; 29 (2): 203–216. DOI: 10.1007/s00467-013-2500-1.
Grayson PC, Kim SY, LaValley M, Choi HK. Hyperuricemia and incident hypertension: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2011 Jan; 63 (1): 102-10. DOI: 10.1002/acr.20344.
Nashar K, Fried LF. Hyperuricemia and the progression of chronic kidney disease: is uric acid a marker or an independent risk factor? Adv Chronic Kidney Dis. 2012; 19 (6): 386–391. DOI: 10.1053/j.ackd.2012.05.004.
Noone DG, Marks SD. Hyperuricemia is associated with hypertension, obesity, and albuminuria in children with chronic kidney disease. J Pediatr. 2013; 162 (1): 128–132.
Rodenbach KE, Schneider MF, Furth SL, et al. Hyperuricemia and progression of CKD in children and adolescents: the chronic kidney disease in children (CKiD) cohort study. Am J Kidney Dis. 2015; 66 (6): 984–992. DOI: 10.1053/j.ajkd.2015.06.015.
Assadi F. Effect of microalbuminuria lowering on regression of left ventricular hypertrophy in children and adolescents with essential hypertension. Pediatr Cardiol. 2007; 28 (1): 27–33. DOI: 10.1007/s00246-006-1390-4.
Conkar S, Yılmaz E, Hacıkara Ş, Bozabalı S, Mir S. Is daytime systolic load an important risk factor for target organ damage in pediatric hypertension? J Clin Hypertens. Greenwich. 2015; 17 (10): 760–6. DOI: 10.1111/jch.12608.
Lande MB, Batisky DL, Kupferman JC, Samuels J, Hooper SR, Falkner B, et al. Neurocognitive function in children with primary hypertension. J Pediatr. 2017; 180: 148–55.e1. DOI: 10.1016/j.jpeds.2016.08.076.
Kupferman JC, Aronson Friedman L, Cox C, Flynn J, Furth S, Warady B, et al. BP control and left ventricular hypertrophy regression in children with CKD. Clin J Am Soc Nephrol. 2014; 25 (1): 167–74. DOI: 10.1681/ASN.2012121197.
Staples A, Wong C. Risk Factors for Progression of Chronic Kidney Disease Curr Opin Pediatr. 2010 Apr; 22 (2): 161–169. DOI: 10.1097/MOP.0b013e328336ebb0.
Deva R, Alias MA, Colville D, Tow FK, Ooi QL. Vision-threatening retinal abnormalities in chronic kidney disease stages 3 to 5. Clin J Am Soc Nephrol. 2011 Aug; 6 (8): 1866-71. DOI: 10.2215/CJN.10321110.
El-Ghany, S. M. A., El-Salam, M. A., Farag, M. M. and El-Ashwah, O. A. (2019) Ocular Changes in Egyptian Children on Regular Hemodialysis. International Journal of Clinical Medicine, 10, 353-362.
Brady TM, Schneider MF, Flynn JT, Cox C, Samuels J. et al.. Carotid Intima-Media Thickness in Children with CKD: Results from the CKiD Study. Clin J Am Soc Nephrol. 2012; 7: 1930–1937. DOI: 10.2215/CJN.0313031.
Sinha MD, Tibby SM, Rasmussen P, et al. Blood pressure control and left ventricular mass in children with chronic kidney disease. Clin J Am Soc Nephrol. 2011; 6 (3): 543–551. DOI: 10.2215/CJN.04690510.
Makarova T. P., Melnikova Yu. S. Echocardiographic parameters of the heart with chronic kidney disease in children and adolescents. Ros Vestn Perinatol i Pediatr 2017; 62: (5): 149–152. DOI: 10.21508/1027–4065–2017–62–5–149–152.
Chen K., Didsbury M., Van Zwieten A., Howell M., Kim S. et al. Neurocognitive and Educational Outcomes in Children and Adolescents with CKD. A Systematic Review and Meta-Analysis. CJASN, March 2018; 13 (3): 387-397; DOI: https://doi.org/10.2215/CJN.09650917.
Staples AO, Greenbaum LA, Smith JM, Gipson DS, Filler G, Warady BA, et al. Association between clinical risk factors and progression of chronic kidney disease in children. Clin J Am Soc Nephrol. 2010; 5: 2172–9. DOI: 10.2215/CJN.07851109.
Kamath N, Iyengar A, George N, Luyckx VA. Risk Factors and Rate of Progression of CKD in Children. Kidney Int Rep 2019; 4: 1472-77. DOI: https://doi.org/10.1016/j.ekir.2019.06.004.
Chaudhuri A, Sutherland SM, Begin B, Salsbery K, McCabe L, Potter D, et al. Role of twenty-four-hour ambulatory blood pressure monitoring in children on dialysis. Clin J Am Soc Nephrol. 2011; 6: 870–6. DOI: 10.2215/CJN.07960910.
Hermida RC, Smolensky MH, Ayala DE, Portaluppi F, Crespo JJ, Fabbian F, et al. Ambulatory blood pressure monitoring recommendations for the diagnosis of adult hypertension, assessment of cardiovascular and other hypertension-associated risk, and attainment of therapeutic goals (summary). Joint recommendations from the International Society for Chronobiology (ISC), American Association of Medical Chronobiology and Chronotherapeutics (AAMCC), Spanish Society of Applied Chronobiology, Chronotherapy, and Vascular Risk (SECAC), Spanish Society of Atherosclerosis (SEA), and Romanian Society of Internal Medicine (RSIM) Clin Investig Arterioscler. 2013; 25: 74–82. DOI: 10.1016/j.arteri.2013.03.002.
Mancia G, Parati G. Ambulatory blood pressure monitoring and organ damage. Hypertension. 2000; 36: 894–900 DOI: 10.1161/01.hyp.36.5.894.
Flynn JT, Daniels SR, Hayman LL, Maahs DM, McCrindle BW, Mitsnefes M, et al. Update: Ambulatory blood pressure monitoring in children and adolescents: A scientific statement from the American Heart Association. Hypertension. 2014; 63: 1116–35.
Franklin SS, Thijs L, Hansen TW, O'Brien E, Staessen JA. White-coat hypertension: New insights from recent studies. Hypertension. 2013; 62: 982–7. DOI: 10.1161/HYPERTENSIONAHA.113.01275.
Urbina E, Alpert B, Flynn J, Hayman L, Harshfield GA, Jacobson M, et al. Ambulatory blood pressure monitoring in children and adolescents: Recommendations for standard assessment: A scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee of the council on cardiovascular disease in the young and the council for high blood pressure research. Hypertension. 2008; 52: 433–51. DOI: 10.1161/HYPERTENSIONAHA.108.190329.
Gupta D, S. Chaturvedi S, S. Chandy S, and Agarwal I Role of 24-h ambulatory blood pressure monitoring in children with chronic kidney disease Indian J Nephrol. 2015; 25 (6): 355-361. DOI: 10.4103/0971-4065.148305.
Olowu WA. Pre-treatment considerations in childhood hypertension due to chronic kidney disease. World J Nephrol. 2015 Nov; 6; 4 (5): 500-10. DOI: 10.5527/wjn.v4.i5.50.
Wheeler DC, Becker GJ. Summary of KDIGO guideline. What do we really know about management of blood pressure in patients with chronic kidney disease? Kidney Int. 2013; 83 (3): 377–383. DOI: 10.1038/ki.2012.425.
Lurbe E, Cifkova R, Cruickshank JK, et al. Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension. J Hypertens. 2009; 27 (9): 1719–1742. DOI: 10.1097/HJH.0b013e32832f4f6b.
Gallibois C. M, Jawa NA, and G Noone DG. Hypertension in pediatric patients with chronic kidney disease: management challenges. Int J Nephrol Renovasc Dis. 2017; 10: 205–213. DOI: 10.2147/IJNRD.S100891.
Rogan JW, Lyszkiewicz DA, Blowey D, Khattak S, Arbus GS, Koren G. A randomized prospective crossover trial of amlodipine in pediatric hypertension. Pediatr Nephrol (Berlin, Germany) 2000; 14 (12): 1083–1087. DOI: 10.1007/s004670000400.
Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017; 140: e20171904 DOI: 10.1542/peds.2017-1904.
Berl T. Review: renal protection by inhibition of the renin-angiotensin-aldosterone system. J Renin Angiotensin Aldosterone Syst. 2009; 10 (1): 1–8. DOI: 10.1177/1470320309102747.
ESCAPE Trial Group, Wühl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, et al. Strict blood-pressure control and progression of renal failure in children. N Engl J Med. 2009; 361 (17): 1639–50. DOI: 10.1056/NEJMoa0902066.
Lou-Meda R, Stiller B, Antonio ZL, Zielinska E, Yap HK, Kang HG. Long-term safety and tolerability of valsartan in children aged 6 to 17 years with hypertension. Pediatr Nephrol. 2019 Mar; 34 (3): 495-506. DOI: 10.1007/s00467-018-4114-0.
Wells T, Frame V, Soffer B, et al. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of enalapril for children with hypertension. J Clin Pharmacol. 2002; 42 (8): 870–880. DOI: 10.1177/009127002401102786.
Trachtman H, Frank R, Mahan JD, et al. Clinical trial of extended-release felodipine in pediatric essential hypertension. Pediatr Nephrol (Berlin, Germany) 2003; 18 (6): 548–553. DOI: 10.1007/s00467-003-1134-0.
Chaturvedi S, Lipszyc DH, Licht C, Craig JC, Parekh R. Pharmacological interventions for hypertension in children. Cochrane Database Syst Rev. 2014; (2): CD008117. DOI: 10.1002/14651858.CD008117.pub2.
Vasavada N, Agarwal R. Role of excess volume in the pathophysiology of hypertension in chronic kidney disease. Kidney Int. 2003; 64 (5): 1772–1779. DOI: 10.1046/j.1523-1755.2003.00273.x.
Blowey DL. Diuretics in the treatment of hypertension. Pediatr Nephrol (Berlin, Germany) 2016; 31 (12): 2223–2233. DOI: 10.1007/s00467-016-3334-4.