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Salt Sensitivity and Nondippers in Chronic Kidney Disease

  • Antihypertensive Therapy: Patient Selection and Special Problems (K Kario and H Rakugi, Section Editors)
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Abstract

High salt-sensitivity and nondipper blood pressure (BP) rhythm are highly associated with each other, because both are caused by impaired renal sodium excretion capability. We proposed that nocturnal hypertension and resultant pressure natriuresis could compensate for daytime sodium retention. If so, high BP may continue until sodium is sufficiently excreted at night. In fact, it takes longer for the night-time BP to fall in patients with more severe renal dysfunction. The time appears to be an essential component of the nondipper BP rhythm and, therefore, we defined the duration as the dipping time. Also, renal function was the sole determinant of a nocturnal BP dip other than age, sex, or BMI. Furthermore, we reported that diuretic therapy or dietary salt restriction, which can prevent sodium retention, restored the circadian BP rhythm into a dipper pattern. Large-scale studies are needed to explore whether these interventions can decrease the risks.

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References

Recently published papers of particular interest have been highlighted as: • Of importance •• Of major importance

  1. Kimura G. Sodium, kidney, and circadian rhythm of blood pressure. Clin Exp Nephrol. 2001;5:13–8.

    Article  Google Scholar 

  2. Kimura G, Brenner BM. Implications of linear pressure-natriuresis relationship and importance of sodium sensitivity in hypertension. J Hypertens. 1997;15:1055–61.

    Article  PubMed  CAS  Google Scholar 

  3. Kimura G, Brenner BM. The renal basis for salt sensitivity in hypertension. In: Laragh JH, Brenner BM, editors. Hypertension pathophysiology, diagnosis, and management. 2nd ed. New York: Raven Press; 1995. p. 1569–88.

    Google Scholar 

  4. Dahl LK, Heine M, Tassinari L. Role of genetic factors in susceptibility to experimental hypertension due to chronic excess salt ingestion. Nature. 1962;194:480–2.

    Article  PubMed  CAS  Google Scholar 

  5. Dahl LK, Heine M. Primary role of renal homografts in setting chronic blood pressure levels in rats. Circ Res. 1975;36:692–6.

    Article  PubMed  CAS  Google Scholar 

  6. Kawasaki T, Delea CS, Bartter FC, Smith H. 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. 1978;64:193–8.

    Article  PubMed  CAS  Google Scholar 

  7. Fujita T, Henry WL, Bartter FC, et al. Factors influencing blood pressure in salt-sensitive patients with hypertension. Am J Med. 1980;69:334–44.

    Article  PubMed  CAS  Google Scholar 

  8. Hollenberg NK, Moore T, Shoback D, et al. Abnormal renal sodium handling in essential hypertension. Relation to failure of renal and adrenal modulation of responses to angiotensin II. Am J Med. 1986;81:412–8.

    Article  PubMed  CAS  Google Scholar 

  9. Sullivan JM, Ratts TE. Sodium sensitivity in human subjects. Hemodynamic and hormonal correlates Hypertension. 1988;11(6 Pt 2):717–23.

    CAS  Google Scholar 

  10. Campese VM, Parise M, Karubian F, Bigazzi R. Abnormal renal hemodynamics in black salt-sensitive patients with hypertension. Hypertension. 1991;18:805–12.

    Article  PubMed  CAS  Google Scholar 

  11. Tuck M, Corry D, Trujillo A. Salt-sensitive blood pressure and exaggerated vascular reactivity in the hypertension of diabetes mellitus. Am J Med. 1990;88:210–6.

    Article  PubMed  CAS  Google Scholar 

  12. Guyton AC. Arterial pressure and hypertension. Circulatory physiology III. Philadelphia: WB Saunders; 1980.

    Google Scholar 

  13. Hall JE, Mizelle HL, Hildebrandt DA, Brands MW. Abnormal pressure natriuresis. A cause or a consequence of hypertension? Hypertension. 1990;15(6 Pt 1):547–59.

    Article  PubMed  CAS  Google Scholar 

  14. Tobian L, Lange J, Azar S. Reduction of natriuretic capacity and renin release in isolated, blood-perfused kidneys of Dahl hypertensive-prone rats. Circ Res. 1978;43(I):I-92–8.

    Google Scholar 

  15. Maddox DA, Bennett CM, Deen WM, et al. Determinants of glomerular filtration in experimental glomerulonephritis in the rat. J Clin Invest. 1975;55:305–18.

    Article  PubMed  CAS  Google Scholar 

  16. Baer PG, Bianchi G. Renal micropuncture study of normotensive and Milan hypertensive rats before and after development of hypertension. Kidney Int. 1978;13:452–66.

    Article  PubMed  CAS  Google Scholar 

  17. Deen WM, Maddox DA, Robertson CR, Brenner BM. Dynamics of glomerular ultrafiltration in the rat. VII. Response to reduced renal mass. Am J Physiol. 1974;227:556–62.

    PubMed  CAS  Google Scholar 

  18. Hostetter TH, Olson JL, Rennke HG, et al. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol. 1981;241:F85–93.

    PubMed  CAS  Google Scholar 

  19. Dworkin LD, Hostetter TH, Rennke HG, Brenner BM. Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension. J Clin Invest. 1984;73:1448–61.

    Article  PubMed  CAS  Google Scholar 

  20. Hostetter TH, Troy JL, Brenner BM. Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int. 1981;19:410–5.

    Article  PubMed  CAS  Google Scholar 

  21. O’Donnell MP, Kasiske BL, Cleary MP, Keane WF. Effects of genetic obesity on renal structure and function in the Zucker rat. II. Micropuncture studies. J Lab Clin Med. 1985;106:605–10.

    PubMed  Google Scholar 

  22. Fukuda M, Munemura M, Usami T, et al. Nocturnal blood pressure is elevated with natriuresis and proteinuria as renal function deteriorates in nephropathy. Kidney Int. 2004;65:621–5.

    Article  PubMed  Google Scholar 

  23. •• Fukuda M, Mizuno M, Yamanaka T. Patients with renal dysfunction require a longer duration until blood pressure dips during the night. Hypertension. 2008;52:1155–60. This paper demonstrates that, as a function of GFR loss, night-time high BP continues for a longer time.

    Article  PubMed  CAS  Google Scholar 

  24. Uzu T, Kimura G. Diuretics shift circadian rhythm of blood pressure from nondipper to dipper in essential hypertension. Circulation. 1999;100:1635–8.

    Article  PubMed  CAS  Google Scholar 

  25. Uzu T, Harada T, Namba T, et al. Thiazide diuretics enhance nocturnal blood pressure fall and reduce proteinuria in immunoglobulin A nephropathy treated with angiotensin II modulators. J Hypertens. 2005;23:861–5.

    Article  PubMed  CAS  Google Scholar 

  26. • Mu S, Shimosawa T, Ogura S. Epigenetic modulation of the renal β-adrenergic-WNK4 pathway in salt-sensitive hypertension. Nat Med. 2011;17:573–80. This paper focused on epigenetic modulation of WNK4 transcription in the development of salt-sensitive hypertension with sympathetic overactivity.

    Article  PubMed  CAS  Google Scholar 

  27. Sanada H, Yatabe J, Midorikawa S, et al. Single-nucleotide polymorphisms for diagnosis of salt-sensitive hypertension. Clin Chem. 2006;52:352–60.

    Article  PubMed  CAS  Google Scholar 

  28. O’Brien E, Sheridan J, O’Malley K. Dippers and nondippers. Lancet. 1988;II:397.

    Article  Google Scholar 

  29. Verdecchia P, Schillaci G, Guerrieri M, et al. Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation. 1990;81:528–36.

    Article  PubMed  CAS  Google Scholar 

  30. Shimada K, Kawamoto A, Matsubayashi K, Ozawa T. Silent cerebrovascular disease in the elderly. Correlation with ambulatory pressure. Hypertension. 1990;16:692–9.

    Article  PubMed  CAS  Google Scholar 

  31. Pickering TG. The clinical significance of diurnal blood pressure variations. Dippers and nondippers. Circulation. 1990;81:700–2.

    Article  PubMed  CAS  Google Scholar 

  32. Verdecchia P, Schillaci G, Porcellati C. Dippers versus nondippers. J Hypertens. 1991;9 Suppl 8:S42–4.

    CAS  Google Scholar 

  33. Verdecchia P, Porcellati C, Schillaci G, et al. Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension. 1994;24:793–801.

    Article  PubMed  CAS  Google Scholar 

  34. Bianchi S, Bigazzi R, Baldari G, et al. Diurnal variations of blood pressure and microalbuminuria in essential hypertension. Am J Hypertens. 1994;7:23–9.

    PubMed  CAS  Google Scholar 

  35. Staessen JA, Thijs L, Fagard R, et al. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators. JAMA. 1999;282:539–46.

    Article  PubMed  CAS  Google Scholar 

  36. Ingelsson E, Björklund-Bodegård K, Lind L, et al. Diurnal blood pressure pattern and risk of congestive heart failure. JAMA. 2006;295(28):2859–66.

    Article  PubMed  CAS  Google Scholar 

  37. Campese VM. Salt sensitivity in hypertension. Renal and cardiovascular implications. Hypertension. 1994;23:531–50.

    Article  PubMed  CAS  Google Scholar 

  38. Cappuccio FP, Strazzullo P, Siani A, Trevisan M. Increased proximal sodium reabsorption is associated with increased cardiovascular risk in men. J Hypertens. 1996;14:909–14.

    Article  PubMed  CAS  Google Scholar 

  39. Bigazzi R, Bianchi S, Baldari G, Campese VM. Clustering of cardiovascular risk factors in salt-sensitive patients with essential hypertension: role of insulin. Am J Hypertens. 1996;9:24–32.

    Article  PubMed  CAS  Google Scholar 

  40. Morimoto A, Uzu T, Fujii T, et al. Sodium sensitivity and cardiovascular events in patients with essential hypertension. Lancet. 1997;350:1734–7.

    Article  PubMed  CAS  Google Scholar 

  41. Whaley-Connell A, Sowers JR. Obesity, insulin resistance, and nocturnal systolic blood pressure. Hypertension. 2008;51:620–1.

    Article  PubMed  CAS  Google Scholar 

  42. Lurbe E, Torro I, Aguilar F, et al. Added impact of obesity and insulin resistance in nocturnal blood pressure elevation in children and adolescents. Hypertension. 2008;51:635–41.

    Article  PubMed  CAS  Google Scholar 

  43. Weinberger MH, Fineberg NS, Fineberg SE, Weinberger M. Salt sensitivity, pulse pressure, and death in normal and hypertensive humans. Hypertension. 2001;37(2):429–32. Part 2.

    Article  PubMed  CAS  Google Scholar 

  44. Luft FC, Miller JZ, Grim CE, et al. Salt sensitivity and resistance of blood pressure. Age and race as factors in physiological responses. Hypertension. 1991;17(I):I102–8.

    Article  PubMed  CAS  Google Scholar 

  45. Parmer RJ, Stone RA, Cervenka JH. Renal hemodynamics in essential hypertension. Racial differences in response to changes in dietary sodium. Hypertension. 1994;24:752–7.

    Article  PubMed  CAS  Google Scholar 

  46. Caplan LR. Strokes in African-Americans. Circulation. 1991;83:1469–71.

    Article  PubMed  CAS  Google Scholar 

  47. Broderick JP, Brott T, Tomsick T, et al. The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites. N Engl J Med. 1992;326:733–6.

    Article  PubMed  CAS  Google Scholar 

  48. Mann JF, Gerstein HC, Pogue J, et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med. 2001;134:629–36.

    PubMed  CAS  Google Scholar 

  49. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39 (2 Suppl 1):S1–266.

    Google Scholar 

  50. Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108:2154–69.

    Article  PubMed  Google Scholar 

  51. Ritz E, McClellan WM. Overview: increased cardiovascular risk in patients with minor renal dysfunction: an emerging issue with far-reaching consequences. J Am Soc Nephrol. 2004;15:513–6.

    Article  PubMed  Google Scholar 

  52. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305.

    Article  PubMed  CAS  Google Scholar 

  53. Uzu T, Ishikawa K, Fujii T, et al. Sodium restriction shifts circadian rhythm of blood pressure from nondipper to dipper in essential hypertension. Circulation. 1997;96:1859–62.

    Article  PubMed  CAS  Google Scholar 

  54. 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;347:797–805.

    Article  PubMed  CAS  Google Scholar 

  55. García-Ortiz L, Gómez-Marcos MA, Martín-Moreiras J, et al. Pulse pressure and nocturnal fall in blood pressure are predictors of vascular, cardiac and renal target organ damage in hypertensive patients (LOD-RISK study). Blood Press Monit. 2009;14:145–51.

    Article  PubMed  Google Scholar 

  56. Davidson MB, Hix JK, Vidt DJ, Brotman DJ. Association of impaired diurnal blood pressure variation with a subsequent decline in glomerular filtration rate. Arch Intern Med. 2006;166:846–52.

    Article  PubMed  Google Scholar 

  57. Redon J, Plancha E, Swift PA, et al. Nocturnal blood pressure and progression to end-stage renal disease or death in nondiabetic chronic kidney disease stages 3 and 4. J Hypertens. 2010;28:602–7.

    Article  PubMed  CAS  Google Scholar 

  58. Torbjörnsdotter TB, Jaremko GA, Berg UB. Nondipping and its relation to glomerulopathy and hyperfiltration in adolescents with type 1 diabetes. Diabetes Care. 2004;27:510–6.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, 467-8601, Japan

    Michio Fukuda & Genjiro Kimura

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  1. Michio Fukuda
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  2. Genjiro Kimura
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Correspondence to Michio Fukuda.

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Fukuda, M., Kimura, G. Salt Sensitivity and Nondippers in Chronic Kidney Disease. Curr Hypertens Rep 14, 382–387 (2012). https://doi.org/10.1007/s11906-012-0286-3

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