Abstract
The importance of salt in the genesis and perpetuation of hypertension is well established. However, within the population, there is considerable heterogeneity in the individual blood pressure response to salt intake. Those with little or no change in their BP in response to salt depletion or loading are considered salt resistant (SR) while those with more significant changes are labeled as salt sensitive (SS). Currently, assessment for SS is impractical, and thus population-wide salt restriction is recommended for all who are hypertensive. This chapter will review definitions of SS, current perspectives on the pathogenesis, and mechanisms involved in inducing SS, explore the phenotype of the SS pediatric hypertensive patient, and outline appropriate interventions.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Albertoni Borghese MF, Ortiz MDC, Marinoni RC et al (2020) Inhibition of endothelin system during the postnatal nephrogenic period in the rat. Its relationship with hypertension and renal disease in adulthood. PloS One 15:e0229756. https://doi.org/10.1371/journal.pone.0229756
Bovée DM, Cuevas CA, Zietse R et al (2020) Salt-sensitive hypertension in chronic kidney disease: distal tubular mechanisms. Am J Physiol Renal Physiol 319:F729–F745. https://doi.org/10.1152/ajprenal.00407.2020
Chaundary P, Velkoska E, Wainford RD (2021) An exploratory analysis of comparative plasma metabolomic and lipidomic profiling in salt-sensitive and salt-resistant individuals from the dietary approaches to stop hypertension sodium trial. J Hypertens. 39(10):1972–1981
Chen J, Gu D, Huang J et al (2009) Metabolic syndrome and salt-sensitivity of blood pressure among persons without diabetes. Lancet 373(9666):829–835. https://doi.org/10.1016/S0140-6736(09)60144-6
Cochat P, Febvey O, Bacchetta J et al (2019) Towards adulthood with a solitary kidney. Pediatr Nephrol 34:2311–2323. https://doi.org/10.1007/s00467-018-4085-1
Cohen JFW, Lehnerd ME, Houser RF, Rimm EB (2017) Dietary approaches to stop hypertension diet, weight status, and blood pressure among children and adolescents: National Health and Nutrition Examination Surveys 2003–2012. J Acad Nutr Diet 117:14371444.e2. https://doi.org/10.1016/j.jand.2017.03.026
Correia-Costa L, Cosme D, Nogueira-Silva L et al (2016) Gender and obesity modify the impact of salt intake on blood pressure in childrenx. J Acad Nutr Diet 117:14371444.e2
Dabelea D, Stafford JM, Mayer-Davis EJ et al (2017) Association of type 1 diabetes vs type 2 diabetes diagnosed during childhood and adolescence with complications during teenage years and young adulthood. JAMA 317:825–835. https://doi.org/10.1001/jama.2017.0686
de Boer MP, Ijzerman RG, de Jongh RT et al (2008) Birth weight relates to salt sensitivity of blood pressure in healthy adults. Hypertension 51:928–932. https://doi.org/10.1161/hypertensionaha.107.101881
Elijovich F, Weinberger MH, Anderson CA et al (2016) Salt sensitivity of blood pressure: a scientific statement from the American Heart Association. Hypertension 68:e7–e46. https://doi.org/10.1161/hyp.0000000000000047
Elijovich F, Kleyman TR, Laffer CL, Kirabo A (2020) Immune mechanisms of dietary salt-induced hypertension and kidney disease: Harry Goldblatt award for early career investigators. Hypertension 78:252–260. https://doi.org/10.1161/HYPERTENSIONAHA.121.16495
Falkner B (2017) Does potassium deficiency contribute to hypertension in children and adolescents? Curr Hypertens Rep 19:37. https://doi.org/10.1007/s11906-017-0733-2
Falkner B, Kushner H (1990) Effect of chronic sodium loading on cardiovascular response in young blacks and whites. Hypertension 15:36–43. https://doi.org/10.1161/01.hyp.15.1.36
Falkner B, Michel S (1997) Blood pressure response to sodium in children and adolescents. Am J Clin Nutr 65(Suppl):618S–621S. https://doi.org/10.1093/ajcn/65.2.618S
Falkner B, Hulman S, Kushner H (1992) Hyperinsulinemia and blood pressure sensitivity to sodium in young blacks. J Am Soc Nephrol 3:940–946. https://doi.org/10.1681/ASN.V34940
Faulkner JL, Belin de Chantemèle EJ (2020) Sex, a major risk factor for salt-sensitive hypertension. Curr Hypertens Rep 22:99. https://doi.org/10.1007/s11906-020-01113-6
Fei K, Rodriguez-Lopez JS, Ramos M et al (2017) Racial and ethnic subgroup disparities in hypertension prevalence, New York City health and nutrition examination survey, 2013–2014. Prev Chronic Dis 14:E33. https://doi.org/10.5888/pcd14.160478
Feng W, Dell’Italia LJ, Sanders PW (2017) Novel paradigms of salt and hypertension. J Am Soc Nephrol 28:1362–1369. https://doi.org/10.1681/ASN.2016080927
Ferguson JF, Aden LA, Barbaro NR et al (2019) High dietary salt-induced dendritic cell activation underlies microbial dysbiosis-associated hypertension. JCI Insight 5:e126241. https://doi.org/10.1172/jci.insight.126241
Forrester T (2004) Historic and early life origins of hypertension in Africans. J Nutr 134:211–216. https://doi.org/10.1093/jn/134.1.211
Garg R, Williams GH, Hurwitz S et al (2011) Low-salt diet increases insulin resistance in healthy subjects. Metabolism 60:965–968. https://doi.org/10.1016/j.metabol.2010.09.005
Graudal NA, Hubeck-Graudal T, Jurgens G (2020) Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride. Cochrane Database Sys Rev 12:Cd004022. https://doi.org/10.1002/14651858.CD004022.pub5
Gu D, Rice T, Wang S et al (2007) Heritability of blood pressure responses to dietary sodium and potassium intake in a Chinese population. Hypertension 50:116–122. https://doi.org/10.1161/HYPERTENSIONAHA.107.088310
Guyton AC (1991) Blood pressure control-special role of the kidneys and body fluids. Science 252:1813–1816. https://doi.org/10.1126/science.2063193
Hall JE, do Carmo JM, da Silva AA et al (2019) Obesity, kidney dysfunction and hypertension: mechanistic links. Nat Rev Nephrol 15:367–385. https://doi.org/10.1038/s41581-019-0145-4
Han S, Wu L, Wang W, Wu X (2019) Trends in dietary nutrients by demographic characteristics and BMI among US adults, 2003–2016. Nutrients 11:2617. https://doi.org/10.3390/nu11112617
Hanevold CD (2021) Salt sensitivity of blood pressure in childhood and adolescence. Pediatr Nephrol https://doi.org/10.1007/s00467-021-05178-6. Epub ahead of print. PMID: 34327584
Hanevold CD, Harshfield GA (2016) Stress and salt sensitivity in childhood hypertension. In: Flynn J, Ingelfinger JR, Redwine K (eds) Pediatric hypertension, 4th edn. Springer International Publishing, pp 1–12
Harshfield GA, Alpert BS, Pulliam DA et al (1991) Sodium excretion and racial differences in ambulatory blood pressure patterns. Hypertension 18:813–818. https://doi.org/10.1161/01.hyp.18.6.813
Harshfield GA, Hanevold CD, Jasti A et al (2018) Angiotensin II and the natriuretic and blood pressure response to mental stress in African Americans. Ethn Dis 28:511–516. https://doi.org/10.18865/ed.28.4.511
Hoorn EJ, Gritter M, Cuevas CA, Fenton RA (2020) Regulation of the renal NaCl cotransporter and its rold in potassium homeostasis. Physiol Rev 100:321–356. https://doi.org/10.1152/physrev.00044.2018
Intersalt Cooperative Research Group (1988) Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. BMJ 297:319–328. https://doi.org/10.1136/bmj.297.6644.319
Kawasaki T, Delea CS, Bartter FC, Smith H (1978) The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Am J Med 64:193–198. https://doi.org/10.1016/0002-9343(78)90045-1
Kurtz TW, DiCarlo SE, Pravenec M, Morris RC (2017) An appraisal of methods recently recommended for testing salt sensitivity of blood pressure. J Am Heart Assoc 6:e005653. https://doi.org/10.1161/jaha.117.005653
Kurtz TW, DiCarlo SE, Pravenec M, Morris RC (2018) The pivotal role of renal vasodysfunction in salt sensitivity and the initiation of salt-induced hypertension. Curr Opin Nephrol Hypertens 27:83–92. https://doi.org/10.1097/mnh.0000000000000394
Kurtz TW, DiCarlo SE, Pravenec M, Morris RC (2021) No evidence of racial disparities in blood pressure salt sensitivity when potassium intake exceeds levels recommended in the US dietary guidelines. Am J Physiol Heart Circ Physiol 320:H1903–H1918, 2021. First published April 2, 2021. https://doi.org/10.1152/ajpheart.00980.2020
Laffer CL, Elijovich F (2013) Differential predictors of insulin resistance in nondiabetic salt-resistant and salt-sensitive subjects. Hypertension 61:707–715. https://doi.org/10.1161/hypertensionaha.111.00423
Laffer CL, Scott RC, Titze JM et al (2016) Hemodynamics and salt-and-water balance link sodium storage and vascular dysfunction in salt-sensitive subjects. Hypertension 68:195–203. https://doi.org/10.1161/hypertensionaha.116.07289
Lankadeva YR, Singh RR, Tare M et al (2014) Loss of a kidney during fetal life: long-term consequences and lessons learned. Am J Physiol Renal Physiol 306:F791–F800. https://doi.org/10.1152/ajprenal.00666.2013
Leyvraz M, Chatelan A, da Costa BR et al (2018) Sodium intake and blood pressure in children and adolescents: a systematic review and meta-analysis of experimental and observational studies. Int J Epidemiol 47:1796–1810. https://doi.org/10.1093/ije/dyy121
Liu Y, Shi M, Dolan J, He J (2020) Sodium sensitivity of blood pressure in Chinese populations. J Hum Hypertens 34:94–107. https://doi.org/10.1038/s41371-018-0152-0
Loria AS, Pollock DM, Pollock JS (2015) Angiotensin II is required to induce exaggerated salt sensitivity in dahl rats exposed to maternal separation. Physiol Rep 3:e12408. https://doi.org/10.14814/phy2.12408
Luyckx VA, Brenner BM (2020) Clinical consequences of developmental programming of low nephron number. Anat Rec (Hoboken) 303:2613–2631. https://doi.org/10.1002/ar.24270
Mahumud RA, Sahle BW, Owusu-Addo E et al (2021) Association of dietary intake, physical activity, and sedentary behaviors with overweight and obesity among 282,213 adolescents in 89 low and middle income to high-income countries. Int J Obes. https://doi.org/10.1038/s41366-021-00908-0. Epub ahead of print
Mattson DL (2019) Immune mechanisms of salt-sensitive hypertension and renal end-organ damage. Nat Rev Nephrol 15:290–300. https://doi.org/10.1038/s41581-019-0121-z
Miller JZ, Weinberger MH, Daugherty SA et al (1988) Blood pressure response to dietary sodium restriction in healthy normotensive children. Am J Clin Nutr 47:113–119. https://doi.org/10.1093/ajcn/47.1.113
Morris RC Jr, Sebastian A, Forman A et al (1999) Normotensive salt sensitivity: effects of race and dietary potassium. Hypertension 33:18–23. https://doi.org/10.1161/01.hyp.33.1.18
Mu JJ, Liu ZQ, Liu WM, Liang YM, Yang DY, Zhu DJ, Wang ZX (2005) Reduction of blood pressure with calcium and potassium supplementation in children with salt sensitivity: a 2-year double-blinded placebo-controlled trial. J Hum Hypertens 19:479–483. https://doi.org/10.1038/sj.jhh.1001854
Mu J, Zheng S, Lian Q, Liu F, Liu Z (2012) Evolution of blood pressure from adolescents to youth in salt sensitives: an18-year follow-up study in Hanzhong children cohort. Nutr J 11:70. https://doi.org/10.1186/1475-2891-11-70
Mutchler SM, Kirabo A, Kleyman TR (2021) Epithelial sodium channel and salt-sensitive hypertension. Hypertension 77:759–767. https://doi.org/10.1161/HYPERTENSIONAHA.120.14481
Nosadini R, Sambataro M, Thomaseth K et al (1993) Role of hyperglycemia and insulin resistance in determining sodium retention in non-insulin-dependent diabetes. Kidney Int 44:139–146. https://doi.org/10.1038/ki.1993.224
Obi IE, McPherson KC, Pollock JS (2019) Childhood adversity and mechanistic links to hypertension risk in adulthood. Br J Pharmacol 176:1932–1950. https://doi.org/10.1111/bph.14576
Ogden CL, Fryar CD, Hales CM et al (2018) Differences in obesity prevalence by demographics and urbanization in US children and adolescents, 2013–2016. JAMA 319:2410–2418. https://doi.org/10.1001/jama.2018.5158
Otani L, Sugimoto N, Misa Kaji M et al (2012) Role of the renin–angiotensin–aldosterone system in the enhancement of salt sensitivity caused by prenatal protein restriction in stroke-prone spontaneously hypertensive rats. J Nutr Biochem 23:892–899. https://doi.org/10.1016/j.jnutbio.2011.04.014
Palacios C, Wigertz K, Martin BR et al (2004) Sodium retention in black and white female adolescents in response to salt intake. J Clin Endocrinol Metab 89:1858–1863. https://doi.org/10.1210/jc.2003-031446
Pauwaert K, Dejonckheere S, Bruneel E et al (2019) The effect of a multidisciplinary weight loss program on renal circadian rhythm in obese adolescents. Eur J Pediatr 178:1849–1858. https://doi.org/10.1007/s00431-019-03456-y
Pavlov TS, Staruschenko A (2017) Involvement of ENaC in the development of salt-sensitive hypertension. Am J Physiol Renal Physiol 313:F135–F140. https://doi.org/10.1152/ajprenal.00427.2016
Perälä MM, Moltchanova E, Kaartinen NE et al (2011) The association between salt intake and adult systolic blood pressure is modified by birth weight. Am J Clin Nutr 93:422–426. https://doi.org/10.3945/ajcn.2010.30022
Pitzer AL, Van Beusecum JP, Kleyman TR, Kirabo A (2020) ENaC in salt-sensitive hypertension: kidney and beyond. Curr Hypertens Rep 22:69. https://doi.org/10.1007/s11906-020-01067-9
Raaijmakers A, Zhang ZY, Claessens J et al (2017) Does extremely low birth weight predispose to low-renin hypertension? Hypertension 69:443–449. https://doi.org/10.1161/hypertensionaha.116.08643
Richardson SI, Freedman BI, Ellison DH, Rodriguez CJ (2013) Salt sensitivity: a review with a focus on non-Hispanic blacks and hispanics. J Am Soc Hypertens 7:170–179. https://doi.org/10.1016/j.jash.2013.01.003
Rios-Leyvraz M, Bovet P, Tabin R et al (2018) Urine spot samples can be used to estimate 24-hour urinary sodium excretion in children. J Nutr 148:1946–1953. https://doi.org/10.1093/jn/nxy211
Rios-Leyvraz M, Bloetzer C, Chatelan A et al (2019) Sodium intake and blood pressure in children with clinical conditions: a systematic review with meta-analysis. J Clin Hypertens (Greenwich) 21:118–126. https://doi.org/10.1111/jch.13436
Rocchini AP, Key J, Bondie D et al (1989) The effect of weight loss on the sensitivity of blood pressure to sodium in obese adolescents. N Engl J Med 321:580–585. https://doi.org/10.1056/nejm198908313210905
Rodan AR (2017) Potassium: friend or foe? Pediatr Nephrol 32:1109–1121. https://doi.org/10.1007/s00467-016-3411-8
Ruta LA, Dickinson H, Thomas MC et al (2010) High-salt diet reveals the hypertensive and renal effects of reduced nephron endowment. Am J Physiol Renal Physiol 298:F1384–F1392. https://doi.org/10.1152/ajprenal.00049.2010
Ruys CA, Rotteveel J, van de Lagemaat M et al (2018) Salt sensitivity of blood pressure at age 8 years in children born preterm. J Hum Hypertens 32:367–376. https://doi.org/10.1038/s41371-018-0045-2
Selvarajah V, Kaisa M, Mäki-Petäjä KM et al (2017) Novel mechanism for buffering dietary salt in humans: effects of salt loading on skin sodium, vascular endothelial growth factor C, and blood pressure. Hypertension 70:930–937. https://doi.org/10.1161/HYPERTENSIONAHA.117.10003
Selvarajah V, Connolly K, McEniery C, Wilkinson I (2018) Skin sodium and hypertension: a paradigm shift? Curr Hypertens Rep 20:94. https://doi.org/10.1007/s11906-018-0892-9 PMID: 30215153
Simonetti GD, Raio L, Surbek D et al (2008) Salt sensitivity of children with low birth weight. Hypertension 52:625–630. https://doi.org/10.1161/hypertensionaha.108.114983
Simonetti GD, Farese S, Aregger F et al (2010) Nocturnal dipping behavior in normotensive white children and young adults in response to changes in salt intake. J Hypertens 28:1027–1033
Song P, Zhang Y, You J et al (2019) Global prevalence of hypertension in children. A systematic review and meta-analysis. JAMA Pediatr 173:1154–1163. https://doi.org/10.1001/jamapediatrics.2019.3310. https://doi.org/10.1161/hypertensionaha.118.11064
Spence JD, Rayner BL (2018) Hypertension in blacks: individualized therapy based on renin/aldosterone phenotyping. Hypertension 72:263–269. https://doi.org/10.1161/hypertensionaha.118.11064
Su S, Wang X, Pollock JS et al (2015) Adverse childhood experiences and blood pressure trajectories from childhood to young adulthood: the Georgia stress and Heart study. Circulation 131:1674–1681. https://doi.org/10.1161/circulationaha.114.013104
Suckling RJ, He FJ, Markandu ND, MacGregor GA (2016) Modest salt reduction lowers blood pressure and albumin excretion in impaired glucose tolerance and type 2 diabetes mellitus: a randomized double-blind trial. Hypertension 67:1189–1195. https://doi.org/10.1161/hypertensionaha.115.06637
Titze J, Lang R, Ilies C et al (2003) Osmotically inactive skin Na+ storage in rats. Am J Physiol Renal Physiol 285:F1108–F1117. https://doi.org/10.1152/ajprenal.00200.2003
Tiwari S, Riazi S, Ecelbarger CA (2007) Insulin’s impact on renal sodium transport and blood pressure in health, obesity, and diabetes. Am J Physiol Renal Physiol 293:F974–F984. https://doi.org/10.1152/ajprenal.00149.2007
Tu W, Eckert GJ, Hannon TS et al (2014) Racial differences in sensitivity of blood pressure to aldosterone. Hypertension 63:1212–1218. https://doi.org/10.1161/hypertensionaha.113.02989
Tu W, Li R, Bhalla V et al (2018) Age-related blood pressure sensitivity to aldosterone in blacks and whites. Hypertension 72:247–252. https://doi.org/10.1161/hypertensionaha.118.11014
U.S. Department of Agriculture and U.S. Department of Health and Human Services (2020) Dietary Guidelines for Americans, 2020–2025. 9th edn. Appendix 1: Nutritional Goals for Age-Sex Groups, page 131–133 Available at DietaryGuidelines.gov
Uzu T, Kimura G, Yamauchi A et al (2006) Enhanced sodium sensitivity and disturbed circadian rhythm of blood pressure in essential hypertension. J Hypertens 24:1627–1632. https://doi.org/10.1097/01.hjh.0000239299.71001.77
Weinberger MH, Fineberg NS (1991) Sodium and volume sensitivity of blood pressure. Age and pressure change over time. Hypertension 18:67–71. https://doi.org/10.1161/01.hyp.18.1.67
Weinberger MH, Miller JZ, Luft FC et al (1986) Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension 8:II127–II134. https://doi.org/10.1161/01.hyp.8.6_pt_2.ii127
Wesseling S, Koeners MP, Joles JA (2011) Salt sensitivity of blood pressure: developmental and sex-related effects. Am J Clin Nutr 94(suppl):1928S–1932S. https://doi.org/10.3945/ajcn.110.000901
Wilck N, Matus MG, Kearney SM et al (2017) Salt-responsive gut commensal modulates T(H)17 axis and disease. Nature 551(7682):585–589. https://doi.org/10.1038/nature24628
Wilson DK, Bayer L, Krishnamoorthy JS, Ampey-Thornhill G, Nicholson SC, Sica DA (1999a) The prevalence of salt sensitivity in an African-American adolescent population. Ethn Dis 9:350–358. PMID: 10600057
Wilson DK, Sica DA, Miller SB (1999b) Effects of potassium on blood pressure in salt-sensitive and salt-resistant black adolescents. Hypertension 34:181–186. https://doi.org/10.1161/01.hyp.34.2.181
Yang Q, Zhang Z, Kuklina EV et al (2012) Sodium intake and blood pressure among US children and adolescents. Pediatrics 130:611–619. https://doi.org/10.1542/peds.2011-3870
Yatabe MS, Yatabe J, Yoneda M et al (2010) Salt sensitivity is associated with insulin resistance, sympathetic overactivity, and decreased suppression of circulating renin activity in lean patients with essential hypertension. Am J Clin Nutr 92:77–82. https://doi.org/10.3945/ajcn.2009.29028
Ye T, Liu ZQ, Mu JJ et al (2004) Blood pressure change with age in salt-sensitive teenagers. Chin Med Sci J 19:248–251. PMID: 15669180
Yel S, Günay N, Pınarbaşı AS et al (2021) Do children with solitary or hypofunctioning kidney have the same prevalence for masked hypertension? Pediatr Nephrol 36:1833–1841. https://doi.org/10.1007/s00467-020-04896-7
Yu Z, Eckert GJ, Liu H et al (2013) Adiposity has unique influence on the renin-aldosterone axis and blood pressure in black children. J Pediatr 163:1317–1322.e1. https://doi.org/10.1016/j.jpeds.2013.06.082
Zhang L, Qi H, Liu Z et al (2020) Construction of a ceRNA coregulatory network and screening of hub biomarkers for salt-sensitive hypertension. J Cell Mol Med 24:7254–7265. https://doi.org/10.1111/jcmm.15285. Epub 2020 May 15
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2023 This is a U.S. Government work and not under copyright protection in the U.S.; foreign copyright protection may apply
About this entry
Cite this entry
Hanevold, C.D. (2023). Salt Sensitivity in Childhood Hypertension. In: Flynn, J.T., Ingelfinger, J.R., Brady, T.M. (eds) Pediatric Hypertension. Springer, Cham. https://doi.org/10.1007/978-3-031-06231-5_18
Download citation
DOI: https://doi.org/10.1007/978-3-031-06231-5_18
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-06230-8
Online ISBN: 978-3-031-06231-5
eBook Packages: MedicineReference Module Medicine