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Pathophysiological Insights of Hypertension in Patients with Chronic Kidney Disease

  • Faruk TurgutEmail author
  • Mustafa Yaprak
  • Faruk Tokmak
Chapter

Abstract

Hypertension is a multi-organ disease, and kidneys play a central role in the development of hypertension, although the kidneys are also being a target organ for hypertension-induced damage. The association between hypertension and chronic kidney disease (CKD) is well known. The prevalence of hypertension increases and control of hypertension becomes more difficult as kidney functions decline. Understanding of the pathophysiology of hypertension is critical for the management of hypertension in CKD. However, there are large gaps in our understanding of pathogenesis and treatment of CKD-related hypertension. Basically, high blood pressure is caused by an increase in cardiac output and/or increase of total peripheral resistance. Both can be deteriorated by a variety of different mechanisms in CKD. Sodium retention and extracellular volume expansion are important, but not the only factors contributing to hypertension seen in CKD. Humoral factors such as renin-angiotensin-aldosterone system, endothelin, and non-humoral factors such as mineral bone disorders may also play a major role in the pathogenesis of hypertension in CKD.

Keywords

Hypertension Chronic kidney disease Blood pressure Sodium retention Volume overload The Renin Angiotensin Aldosterone System Sympathetic nervous system Endothelins Oxidative stress Nitric oxide Drugs 

References

  1. 1.
    US Renal Data System USRDS 2010 Annual Data Report. Atlas of chronic kidney disease and end-stage renal disease in the United States. Bethesda: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2010.Google Scholar
  2. 2.
    Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32(5 Suppl 3):S112–9.CrossRefPubMedGoogle Scholar
  3. 3.
    USRD 2009. Atlas of Chronic Kidney Disease in the United States. Am J Kidney Dis. 2010;55(Suppl 1):S1–420.Google Scholar
  4. 4.
    Kanbay M, Turgut F, Uyar ME, Akcay A, Covic A. Causes and mechanisms of nondipping hypertension. Clin Exp Hypertens. 2008;30(7):585–97.CrossRefPubMedGoogle Scholar
  5. 5.
    Borrelli S, De Nicola L, Stanzione G, Conte G, Minutolo R. Resistant hypertension in nondialysis chronic kidney disease. Int J Hypertens. 2013;2013:929183.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Bangash F, Agarwal R. Masked hypertension and white-coat hypertension in chronic kidney disease: a meta-analysis. Clin J Am Soc Nephrol. 2009;4(3):656–64.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ridao N, Luño J, García de Vinuesa S, Gómez F, Tejedor A, Valderrábano F. Prevalence of hypertension in renal disease. Nephrol Dial Transplant. 2001;16(Suppl 1):70–3.CrossRefPubMedGoogle Scholar
  8. 8.
    Muntner P, Anderson A, Charleston J, Chen Z, Ford V, Makos G, et al. Hypertension awareness, treatment, and control in adults with CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) study. Am J Kidney Dis. 2010;55(3):441–51.CrossRefPubMedGoogle Scholar
  9. 9.
    Curtis JJ, Luke RG, Dustan HP, Kashgarian M, Whelchel JD, Jones P, et al. Remission of essential hypertension after renal transplantation. N Engl J Med. 1983;309(17):1009–15.CrossRefPubMedGoogle Scholar
  10. 10.
    Herrera M, Coffman TM. The kidney and hypertension: novel insights from transgenic models. Curr Opin Nephrol Hypertens. 2012;21(2):171–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Keller G, Zimmer G, Mall G, Ritz E, Amann K. Nephron number in patients with primary hypertension. N Engl J Med. 2003;348(2):101–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Widgren BR, Herlitz H, Hedner T, Berglund G, Wikstrand J, Jonsson O, et al. Blunted renal sodium excretion during acute saline loading in normotensive men with positive family histories of hypertension. Am J Hypertens. 1991;4(7 Pt 1):570–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Todd AS, Macginley RJ, Schollum JB, Johnson RJ, Williams SM, Sutherland WH, et al. Dietary salt loading impairs arterial vascular reactivity. Am J Clin Nutr. 2010;91(3):557–64.CrossRefPubMedGoogle Scholar
  14. 14.
    Al-Solaiman Y, Jesri A, Zhao Y, Morrow JD, Egan BM. Low-Sodium DASH reduces oxidative stress and improves vascular function in salt-sensitive humans. J Hum Hypertens. 2009;23(12):826–35.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    McMahon EJ, Bauer JD, Hawley CM, Isbel NM, Stowasser M, Johnson DW, et al. A randomized trial of dietary sodium restriction in CKD. J Am Soc Nephrol. 2013;24(12):2096–103.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Vasavada N, Agarwal R. Role of excess volume in the pathophysiology of hypertension in chronic kidney disease. Kidney Int. 2003;64(5):1772–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Saad E, Charra B, Raj DS. Hypertension control with daily dialysis. Semin Dial. 2004;17(4):295–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Ok E, Duman S, Asci G, Tumuklu M, Onen Sertoz O, Kayikcioglu M, et al. Comparison of 4- and 8-h dialysis sessions in thrice-weekly in-centre haemodialysis: a prospective, case-controlled study. Nephrol Dial Transplant. 2011;26(4):1287–96.CrossRefPubMedGoogle Scholar
  19. 19.
    Günal AI, Duman S, Ozkahya M, Töz H, Asçi G, Akçiçek F, et al. Strict volume control normalizes hypertension in peritoneal dialysis patients. Am J Kidney Dis. 2001;37(3):588–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Kobori H, Nangaku M, Navar LG, Nishiyama A. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev. 2007;59(3):251–87.CrossRefPubMedGoogle Scholar
  21. 21.
    Weidmann P, Maxwell MH, Lupu AN, Lewin AJ, Massry SG. Plasma renin activity and blood pressure in terminal renal failure. N Engl J Med. 1971;285(14):757–62.CrossRefPubMedGoogle Scholar
  22. 22.
    Vaughan ED, Carey RM, Ayers CR, Peach MJ. Hemodialysis-resistant hypertension: control with an orally active inhibitor of angiotensin-converting enzyme. J Clin Endocrinol Metab. 1979;48(5):869–71.CrossRefPubMedGoogle Scholar
  23. 23.
    Briet M, Schiffrin EL. Vascular actions of aldosterone. J Vasc Res. 2013;50(2):89–99.CrossRefPubMedGoogle Scholar
  24. 24.
    Greene EL, Kren S, Hostetter TH. Role of aldosterone in the remnant kidney model in the rat. J Clin Invest. 1996;98(4):1063–8.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ibrahim HN, Hostetter TH. The renin-aldosterone axis in two models of reduced renal mass in the rat. J Am Soc Nephrol. 1998;9(1):72–6.PubMedGoogle Scholar
  26. 26.
    Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm M, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376(9756):1903–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Converse RL, Jacobsen TN, Toto RD, Jost CM, Cosentino F, Fouad-Tarazi F, et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992;327(27):1912–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Joles JA, Koomans HA. Causes and consequences of increased sympathetic activity in renal disease. Hypertension. 2004;43(4):699–706.CrossRefPubMedGoogle Scholar
  29. 29.
    Ye S, Zhong H, Duong VN, Campese VM. Losartan reduces central and peripheral sympathetic nerve activity in a rat model of neurogenic hypertension. Hypertension. 2002;39(6):1101–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Richter CM. Role of endothelin in chronic renal failure—developments in renal involvement. Rheumatology (Oxford). 2006;45(Suppl 3):iii36–8.Google Scholar
  31. 31.
    Dunn MJ, Hood VL. Prostaglandins and the kidney. Am J Phys. 1977;233(3):169–84.Google Scholar
  32. 32.
    Kone BC, Baylis C. Biosynthesis and homeostatic roles of nitric oxide in the normal kidney. Am J Phys. 1997;272(5 Pt 2):F561–78.Google Scholar
  33. 33.
    Vaziri ND. Effect of chronic renal failure on nitric oxide metabolism. Am J Kidney Dis. 2001;38(4 Suppl 1):S74–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Xu J, Li G, Wang P, Velazquez H, Yao X, Li Y, et al. Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. J Clin Invest. 2005;115(5):1275–80.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Desir GV. Regulation of blood pressure and cardiovascular function by renalase. Kidney Int. 2009;76(4):366–70.CrossRefPubMedGoogle Scholar
  36. 36.
    Mellen PB, Bleyer AJ, Erlinger TP, Evans GW, Nieto FJ, Wagenknecht LE, et al. Serum uric acid predicts incident hypertension in a biethnic cohort: the atherosclerosis risk in communities study. Hypertension. 2006;48(6):1037–42.CrossRefPubMedGoogle Scholar
  37. 37.
    Menè P, Punzo G. Uric acid: bystander or culprit in hypertension and progressive renal disease? J Hypertens. 2008;26(11):2085–92.CrossRefPubMedGoogle Scholar
  38. 38.
    Kuriyama S, Maruyama Y, Nishio S, Takahashi Y, Kidoguchi S, Kobayashi C, et al. Serum uric acid and the incidence of CKD and hypertension. Clin Exp Nephrol. 2015;19(6):1127–34.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med. 2008;359(17):1811–21.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Vaziri ND. Roles of oxidative stress and antioxidant therapy in chronic kidney disease and hypertension. Curr Opin Nephrol Hypertens. 2004;13(1):93–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Hoorn EJ, Walsh SB, McCormick JA, Zietse R, Unwin RJ, Ellison DH. Pathogenesis of calcineurin inhibitor-induced hypertension. J Nephrol. 2012;25(3):269–75.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Esteva-Font C, Ars E, Guillen-Gomez E, Campistol JM, Sanz L, Jiménez W, et al. Ciclosporin-induced hypertension is associated with increased sodium transporter of the loop of Henle (NKCC2). Nephrol Dial Transplant. 2007;22(10):2810–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Boyle SM, Berns JS. Erythropoietin and resistant hypertension in CKD. Semin Nephrol. 2014;34(5):540–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Touyz RM. New insights into mechanisms of hypertension. Curr Opin Nephrol Hypertens. 2012;21(2):119–21.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of NephrologyMustafa Kemal University, School of MedicineAntakyaTurkey
  2. 2.Department of NephrologyMVZ Gelsenkirchen-BuerGelsenkirchenGermany

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