Skip to main content
SpringerLink
Log in

Hypertension Treatment for Patients with Advanced Chronic Kidney Disease

  • Hypertension (S Taler, Section Editor)
  • Published:
Current Cardiovascular Risk Reports Aims and scope Submit manuscript

Abstract

Chronic kidney disease is common and frequently complicated with hypertension. As a major modifiable risk factor for cardiovascular disease in this high risk population, treatment of hypertension in chronic kidney disease is of paramount importance. We review the epidemiology and pathogenesis of hypertension in chronic kidney disease and then update the latest study results for treatment including salt restriction, invasive endovascular procedures, and pharmacologic therapy. Recent trials draw into question the efficacy of renal artery stenting or renal denervation for hypertension in chronic kidney disease, as well as renin-angiotensin-aldosterone system blockade as first line therapy of hypertension in end stage renal disease. Positive trial results reemphasize salt restriction and challenge the prevailing prejudice against the use of thiazide-like diuretics in advanced chronic kidney disease. Last, clinical practice guidelines are trending away from recommending tight blood pressure control in chronic kidney disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–150.

    Article  Google Scholar 

  2. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298:2038–47.

    Article  PubMed  CAS  Google Scholar 

  3. Debella YT, Giduma HD, Light RP, Agarwal R. Chronic kidney disease as a coronary disease equivalent—a comparison with diabetes over a decade. Clin J Am Soc Nephrol. 2011;6:1385–92.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 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;55:441–51.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Agarwal R. Epidemiology of interdialytic ambulatory hypertension and the role of volume excess. Am J Nephrol. 2011;34:381–90.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Pannier B, Guerin AP, Marchais SJ, Safar ME, London GM. Stiffness of capacitive and conduit arteries: prognostic significance for end-stage renal disease patients. Hypertension. 2005;45:592–6.

    Article  PubMed  CAS  Google Scholar 

  7. Iliescu EA, Yeates KE, Holland DC. Quality of sleep in patients with chronic kidney disease. Nephrol Dial Transplant. 2004;19:95–9.

    Article  PubMed  Google Scholar 

  8. Lazarus JM, Hampers C, Merrill JP. Hypertension in chronic renal failure. Treatment with hemodialysis and nephrectomy. Arch Intern Med. 1974;133:1059–66.

    Article  PubMed  CAS  Google Scholar 

  9. Murphy RJ. The effect of “rice diet” on plasma volume and extracellular fluid space in hypertensive subjects. J Clin Invest. 1950;29:912–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Schalekamp MA, Beevers DG, Briggs JD, Brown JJ, Davies DL, Fraser R, et al. Hypertension in chronic renal failure. An abnormal relation between sodium and the renin-angiotensin system. Am J Med. 1973;55:379–90.

    Article  PubMed  CAS  Google Scholar 

  11. Converse Jr 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;327:1912–8.

    Article  PubMed  Google Scholar 

  12. Desir GV. Renalase deficiency in chronic kidney disease, and its contribution to hypertension and cardiovascular disease. Curr Opin Nephrol Hypertens. 2008;17:181–5.

    Article  PubMed  CAS  Google Scholar 

  13. Vallance P, Leiper J. Cardiovascular biology of the asymmetric dimethylarginine: dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol. 2004;24:1023–30.

    Article  PubMed  CAS  Google Scholar 

  14. Shichiri M, Hirata Y, Ando K, Emori T, Ohta K, Kimoto S, et al. Plasma endothelin levels in hypertension and chronic renal failure. Hypertension. 1990;15:493–6.

    Article  PubMed  CAS  Google Scholar 

  15. Weber MA, Black H, Bakris G, Krum H, Linas S, Weiss R, et al. A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;374:1423–31.

    Article  PubMed  CAS  Google Scholar 

  16. de Zeeuw D, Coll B, Andress D, Brennan JJ, Tang H, Houser M, et al. The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy. J Am Soc Nephrol. 2014;25:1083–1093.

  17. Krapf R, Hulter HN. Arterial hypertension induced by erythropoietin and erythropoiesis-stimulating agents (ESA). Clin J Am Soc Nephrol. 2009;4:470–80.

    Article  PubMed  CAS  Google Scholar 

  18. Bode-Boger SM, Boger RH, Kuhn M, Radermacher J, Frolich JC. Recombinant human erythropoietin enhances vasoconstrictor tone via endothelin-1 and constrictor prostanoids. Kidney Int. 1996;50:1255–61.

    Article  PubMed  CAS  Google Scholar 

  19. Pimenta E, Gaddam KK, Oparil S, Aban I, Husain S, Dell’Italia LJ, et al. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Hypertension. 2009;54:475–81.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Suckling RJ, He FJ, Macgregor GA. Altered dietary salt intake for preventing and treating diabetic kidney disease. Cochrane Database Syst Rev. 2010;12:1–49.

  21. 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;24:2096–103. This well-designed clinical trial demonstrates the efficacy of low sodium diet for reducing blood pressure in chronic kidney disease.

    Article  PubMed  CAS  Google Scholar 

  22. Spencer AG, Labonte ED, Rosenbaum DP, Plato CF, Carreras CW, Leadbetter MR, et al. Intestinal inhibition of the Na+/H+ exchanger 3 prevents cardiorenal damage in rats and inhibits Na+ uptake in humans. Sci Transl Med. 2014;6:227–36. This is a proof of concept study in animals, which shows that tenepanor, a nonabsorbable drug to reduce intestinal Na absorption can improve outcomes in animals. Preliminary studies in humans shows that this drug is effective in reducing gut Na absorption.

    Article  Google Scholar 

  23. Agarwal R, Alborzi P, Satyan S, Light RP. Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized, controlled trial. Hypertension. 2009;53:500–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Agarwal R, Weir MR. Dry-weight: a concept revisited in an effort to avoid medication-directed approaches for blood pressure control in hemodialysis patients. Clin J Am Soc Nephrol. 2010;5:1255–60.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Krautzig S, Janssen U, Koch KM, Granolleras C, Shaldon S. Dietary salt restriction and reduction of dialysate sodium to control hypertension in maintenance haemodialysis patients. Nephrol Dial Transplant. 1998;13:552–3.

    Article  PubMed  CAS  Google Scholar 

  26. Tandon T, Sinha AD, Agarwal R. Shorter delivered dialysis times associate with a higher and more difficult to treat blood pressure. Nephrol Dial Transplant. 2013;28:1562–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Chertow GM, Levin NW, Beck GJ, Depner TA, Eggers PW, Gassman JJ, et al. In-center hemodialysis six times per week vs three times per week. N Engl J Med. 2010;363:2287–300.

    Article  PubMed  CAS  Google Scholar 

  28. van Ampting JM, Penne EL, Beek FJ, Koomans HA, Boer WH, Beutler JJ. Prevalence of atherosclerotic renal artery stenosis in patients starting dialysis. Nephrol Dial Transplant. 2003;18:1147–51.

    Article  PubMed  Google Scholar 

  29. van Jaarsveld BC, Krijnen P, Pieterman H, Derkx FH, Deinum J, Postma CT, et al. The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group. N Engl J Med. 2000;342:1007–14.

    Article  PubMed  Google Scholar 

  30. Cooper CJ, Murphy TP, Cutlip DE, Jamerson K, Henrich W, Reid DM, et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2014;370:13–22. This large randomized trial shows no benefit to renal artery stenting for cardiovascular events and only a small benefit for hypertension in chronic kidney disease.

    Article  PubMed  CAS  Google Scholar 

  31. Wheatley K, Ives N, Gray R, Kalra PA, Moss JG, Baigent C, et al. Revascularization vs medical therapy for renal-artery stenosis. N Engl J Med. 2009;361:1953–62.

    Article  PubMed  Google Scholar 

  32. Bax L, Woittiez AJ, Kouwenberg HJ, Mali WP, Buskens E, Beek FJ, et al. Stent placement in patients with atherosclerotic renal artery stenosis and impaired renal function: a randomized trial. Ann Intern Med. 2009;150:840–1.

    Article  PubMed  Google Scholar 

  33. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:1275–81.

    Article  PubMed  Google Scholar 

  34. Bhatt DL, Kandzari DE, O’Neill WW, D’Agostino R, Flack JM, Katzen BT, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393–401. This blinded clinical trial shows renal denervation provides no blood pressure benefit in resistant hypertension.

    Article  PubMed  CAS  Google Scholar 

  35. Schlaich MP, Bart B, Hering D, Walton A, Marusic P, Mahfoud F, et al. Feasibility of catheter-based renal nerve ablation and effects on sympathetic nerve activity and blood pressure in patients with end-stage renal disease. Int J Cardiol. 2013;168:2214–20.

    Article  PubMed  Google Scholar 

  36. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507–20.

    Article  PubMed  CAS  Google Scholar 

  37. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int Suppl. 2012;2:337–414.

    Article  Google Scholar 

  38. Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckworth W, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369:1892–903.

    Article  PubMed  CAS  Google Scholar 

  39. Agarwal R, Sinha AD. Thiazide diuretics in advanced chronic kidney disease. J Am Soc Hypertens. 2012;6:299–308.

    Article  PubMed  CAS  Google Scholar 

  40. Agarwal R, Sinha AD, Pappas MK, Ammous F. Chlorthalidone for poorly controlled hypertension in chronic kidney disease: an interventional pilot study. Am J Nephrol. 2014;39:171–82. This uncontrolled pilot trial demonstrates the potential efficacy of thiazide-like diuretics in advanced chronic kidney disease.

    Article  PubMed  CAS  Google Scholar 

  41. Cirillo M, Marcarelli F, Mele AA, Romano M, Lombardi C, Bilancio G. Parallel-group 8-week study on chlorthalidone effects in hypertensives with low kidney function. Hypertension. 2014;63:692–7. This uncontrolled pilot trial demonstrates the potential efficacy of thiazide-like diuretics in chronic kidney disease.

    Article  PubMed  CAS  Google Scholar 

  42. Agarwal R, Sinha AD. Cardiovascular protection with antihypertensive drugs in dialysis patients: systematic review and meta-analysis. Hypertension. 2009;53:860–6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  43. Heerspink HJ, Ninomiya T, Zoungas S, de Zeeuw D, Grobbee DE, Jardine MJ, et al. Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2009;373:1009–15.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Agarwal R, Sinha AD, Pappas MK, Abraham TN, Tegegne GG. Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized controlled trial. Nephrol Dial Transplant. 2014;29:672–81. This large hemodialysis clinical trial demonstrates the superiority of atenolol over lisinopril for treating hypertension.

    Article  PubMed  CAS  Google Scholar 

  45. Iseki K, Arima H, Kohagura K, Komiya I, Ueda S, Tokuyama K, et al. Effects of angiotensin receptor blockade (ARB) on mortality and cardiovascular outcomes in patients with long-term haemodialysis: a randomized controlled trial. Nephrol Dial Transplant. 2013;28:1579–89. This large hemodialysis clinical trial finds no benefit from olmesartan vs other antihypertensives for treating hypertension.

    Article  PubMed  CAS  Google Scholar 

  46. Kovesdy CP, Bleyer AJ, Molnar MZ, Ma JZ, Sim JJ, Cushman WC, et al. Blood pressure and mortality in U.S. Veterans with chronic kidney disease: a cohort study. Ann Intern Med. 2013;159:233–42. This large retrospective cohort study shows an association between systolic blood pressure less than 130 mmHg and mortality in chronic kidney disease.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Zager PG, Nikolic J, Brown RH, Campbell MA, Hunt WC, Peterson D, et al. “U” curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc. Kidney Int. 1998;54:561–9.

    Article  PubMed  CAS  Google Scholar 

  48. Amar J, Vernier I, Rossignol E, Bongard V, Arnaud C, Conte JJ, et al. Nocturnal blood pressure and 24-hour pulse pressure are potent indicators of mortality in hemodialysis patients. Kidney Int. 2000;57:2485–91.

    Article  PubMed  CAS  Google Scholar 

  49. Sheikh S, Sinha AD, Agarwal R. Home blood pressure monitoring: how good a predictor of long-term risk? Curr Hypertens Rep. 2011;13:192–9.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Rajiv Agarwal and Arjun Sinha declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

Author information

Authors and Affiliations

  1. Richard L. Roudebush VA Medical Center, 111N, 1481 West 10th St, Indianapolis, IN, 46202, USA

    Arjun D. Sinha & Rajiv Agarwal

  2. Division of Nephrology, Indiana University School of Medicine, 111N, 1481 West 10th St, Indianapolis, IN, 46202, USA

    Arjun D. Sinha & Rajiv Agarwal

Authors
  1. Arjun D. Sinha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajiv Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajiv Agarwal.

Additional information

This article is part of the Topical Collection on Hypertension

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sinha, A.D., Agarwal, R. Hypertension Treatment for Patients with Advanced Chronic Kidney Disease. Curr Cardiovasc Risk Rep 8, 400 (2014). https://doi.org/10.1007/s12170-014-0400-y

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s12170-014-0400-y

Keywords

Search

Navigation