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Treatment of Hypertension in Chronic Kidney Disease

  • Antihypertensive Agents: Mechanisms of Drug Action (ME Ernst, Section Editor)
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Abstract

Purpose of Review

Chronic kidney disease (CKD) is recognized as a worldwide epidemic. Hypertension commonly coexists with CKD and its prevalence is progressively increasing as kidney function declines.

Recent Findings

For patients with established CKD and/or diabetes with albuminuria, the updated hypertension guidelines have recommended a blood pressure (BP) goal < 130/80 mmHg. Blood pressure level above 130/80 mmHg in CKD patients requires lifestyle modifications and multiple antihypertensive medications. According to recent guidelines, angiotensin-converting enzyme (ACE) inhibitors should be the drugs of first choice. Angiotensin II receptor blockers (ARBs) should be used if the ACE inhibitor is not tolerated. Non-dihydropyridine CCBs consistently reduce albuminuria and slow the decline in kidney function. Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD patients but always in combination with a RAAS blocker. Diuretics are commonly used and represent the cornerstone in the management of CKD patients. All the other agents are used when treatment with the other primary agents have failed.

Summary

In patients with CKD, an intensive BP goal < 130/80 mmHg has been recommended. We review current treatment options.

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References

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

  1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015;131:e29–322.

    Article  PubMed  Google Scholar 

  2. 2017 USRDS Annual Data Report, Volume 1—CKD in the United States available online 10 April 2018.

  3. Taler SJ, Agarwal R, Bakris GL, Flynn JT, Nilsson PM, Rahman M, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis. 2013;62:201–13.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 2008 USRDS Annual Data Report 2007 Incidence and prevalence of CKD: http//www.usrds.org-2007.htm. Available on line 2 march 2018.

  5. Egan BM, Li J, Hutchison FN, Ferdinand KC. Hypertension in the United States, 1999 to 2012: progress toward healthy people 2020 goals. Circulation. 2014;130:1692–9.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 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  Google Scholar 

  7. KDOQI Clinical Practice Guideline for Diabetes and CKD. Update. Am J Kidney Dis. 2012;2012(60):850–86.

    Google Scholar 

  8. Sarafidis PA, Li S, Chen SC, Collins AJ, Brown WW, Klag MJ, et al. Hypertension awareness, treatment, and control in chronic kidney disease. Am J Med. 2008;121:332–40.

    Article  PubMed  Google Scholar 

  9. Tanner RM, Calhoun DA, Bell EK, Bowling CB, Gutierrez OM, Irvin MR, et al. Prevalence of apparent treatment-resistant hypertension among individuals with CKD. Clin J Am Soc Nephrol. 2013;8:1583–90.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Bakris GL. Protecting renal function in the hypertensive patient: clinical guidelines. Am J Hypertens. 2005;18:112S–9S.

    Article  PubMed  Google Scholar 

  11. Kalaitzidis R, Li S, Wang C, Chen SC, McCullough PA, Bakris GL. Hypertension in early-stage kidney disease: an update from the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis. 2009;53:S22–31.

    Article  PubMed  Google Scholar 

  12. Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Ford CE, et al. Blood pressure and end-stage renal disease in men. N Engl J Med. 1996;334:13–8.

    Article  PubMed  CAS  Google Scholar 

  13. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison HC, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2017; https://doi.org/10.1161/HYP.0000000000000066.

  14. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31:1281–357.

    Article  PubMed  CAS  Google Scholar 

  15. 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 

  16. •• Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes 2018. Diabetes Care. 2018;41(Suppl 1):S86-S104. The paper shows the efficacy of controlling individual cardiovascular risk factors in preventing or slowing atherosclerotic cardiovascular disease in patients with diabetes.

  17. Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575–85.

    Article  PubMed  CAS  Google Scholar 

  18. Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370:829–40.

    Article  PubMed  CAS  Google Scholar 

  19. de Galan BE, Perkovic V, Ninomiya T, Pillai A, Patel A, Cass A, et al. Lowering blood pressure reduces renal events in type 2 diabetes. J Am Soc Nephrol. 2009;20:883–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, et al. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995;123:754–62.

    Article  PubMed  CAS  Google Scholar 

  21. Wright JT Jr, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002;288:2421–31.

    Article  PubMed  CAS  Google Scholar 

  22. Ruggenenti P, Perna A, Loriga G, Ganeva M, Ene-Iordache B, Turturro M, et al. Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial. Lancet. 2005;365:939–46.

    Article  PubMed  Google Scholar 

  23. Upadhyay A, Earley A, Haynes SM, Uhlig K. Systematic review: blood pressure target in chronic kidney disease and proteinuria as an effect modifier. Ann Intern Med. 2011;154:541–8.

    Article  PubMed  Google Scholar 

  24. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103–16.

    Article  PubMed  CAS  Google Scholar 

  25. •• Cheung AK, Rahman M, Reboussin DM, Craven TE, Greene T, Kimmel PL, et al. Effects of intensive BP control in CKD. J Am Soc Nephrol. 2017;28:2812–23. The study shows a prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. Targeting an SBP < 120 mmHg compared with < 140 mmHg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.

    Article  PubMed  PubMed Central  Google Scholar 

  26. •• Tsai WC, Wu HY, Peng YS, Yang JY, Chen HY, Chiu YL, et al. Association of intensive blood pressure control and kidney disease progression in nondiabetic patients with chronic kidney disease: a systematic review and meta-analysis. JAMA Intern Med. 2017;177:792–9. The study shows that targeting BP below the current standard did not provide additional benefit for renal outcomes compared with standard treatment in patients with CKD without diabetes.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kanno A, Metoki H, Kikuya M, Terawaki H, Hara A, Hashimoto T, et al. Usefulness of assessing masked and white-coat hypertension by ambulatory blood pressure monitoring for determining prevalent risk of chronic kidney disease: the Ohasama study. Hypertens Res. 2010;33:1192–8.

    Article  PubMed  Google Scholar 

  28. • de Boer IH, Bangalore S, Benetos A, Davis AM, Michos ED, Muntner P, et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care. 2017;40:1273–84. This position statement is intended to update the assessment and treatment of hypertension among people with diabetes.

    Article  PubMed  Google Scholar 

  29. Bakris GL. The implications of blood pressure measurement methods on treatment targets for blood pressure. Circulation. 2016;134:904–5.

    Article  PubMed  Google Scholar 

  30. •• Pengo MF, Ioratti D, Bisogni V, Ravarotto V, Rossi B, Bonfante L, et al. Patients with chronic kidney disease short term blood pressure variability is associated with the presence and severity of sleep disorders. Kidney Blood Press Res. 2017;42:804–15. The study shows that sleep disturbances alter blood pressure profiles in CKD patients and impaired sleep quality increases blood pressure variability and might contribute to their disease progression and worsen prognosis.

    Article  PubMed  Google Scholar 

  31. Omboni S, Gazzola T, Carabelli G, Parati G. Clinical usefulness and cost effectiveness of home blood pressure telemonitoring: meta-analysis of randomized controlled studies. J Hypertens. 2013;31:455–67.

    Article  PubMed  CAS  Google Scholar 

  32. •• Grams ME, Sang Y, Ballew SH, Carrero JJ, Djurdjev O, HJL H, et al. Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int. 2018 https://doi.org/10.1016/j.kint.2018.01.009. Developed 2- and 4-year models of the probability and timing of kidney failure requiring kidney replacement therapy, a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD from the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 mL/min/1.73m 2 .

  33. •• Eckardt K-U, Bansal N, Coresh J, Evans M, Grams ME, Herzog CA. Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4D): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2018 https://doi.org/10.1016/j.kint.2018.02.006. A Controversies Conference with an international expert group organaized by Kidney Disease: Improving Global Outcomes (KDIGO) for the outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy in CKD patients.

  34. Kalaitzidis RG, Bakris GL. Pros and cons of aggressive blood pressure lowering in patients with type 2 diabetes. Curr Vasc Pharmacol. 2012;10:156–61.

    Article  PubMed  CAS  Google Scholar 

  35. Eijkelkamp WB, Zhang Z, Remuzzi G, Parving HH, Cooper ME, Keane WF, et al. Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy: post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial. J Am Soc Nephrol. 2007;18:1540–6.

    Article  PubMed  CAS  Google Scholar 

  36. Navaneethan SD, Schold JD, Arrigain S, Jolly SE, Nally JV Jr. Cause-specific deaths in non-Dialysis-dependent CKD. J Am Soc Nephrol. 2015;26:2512–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36:646–61.

    Article  PubMed  CAS  Google Scholar 

  38. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–60.

    Article  PubMed  CAS  Google Scholar 

  39. Bakris GL, Weir MR, Shanifar S, Zhang Z, Douglas J, van Dijk DJ, et al. Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study. Arch Intern Med. 2003;163:1555–65.

    Article  PubMed  Google Scholar 

  40. Schmieder RE, Hilgers KF, Schlaich MP, Schmidt BM. Renin-angiotensin system and cardiovascular risk. Lancet. 2007;369:1208–19.

    Article  PubMed  CAS  Google Scholar 

  41. Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008;148:30–48.

    Article  PubMed  Google Scholar 

  42. Ruggenenti P, Fassi A, Ilieva A, Iliev IP, Chiurchiu C, Rubis N, et al. Effects of verapamil added-on trandolapril therapy in hypertensive type 2 diabetes patients with microalbuminuria: the BENEDICT-B randomized trial. J Hypertens. 2011;29:207–16.

    Article  PubMed  CAS  Google Scholar 

  43. Haller H, Ito S, Izzo JL Jr, Januszewicz A, Katayama S, Menne J, et al. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med. 2011;364:907–17.

    Article  PubMed  CAS  Google Scholar 

  44. Kalaitzidis RG, Bakris GL. The current state of RAAS blockade in the treatment of hypertension and proteinuria. Curr Cardiol Rep. 2009;11:436–42.

    Article  PubMed  Google Scholar 

  45. Kalaitzidis RG, Bakris GL. Should proteinuria reduction be the criterion for antihypertensive drug selection for patients with kidney disease? Curr Opin Nephrol Hypertens. 2009;18:386–91.

    Article  PubMed  CAS  Google Scholar 

  46. •• Schievink B, Kropelin T, Mulder S, Parving HH, Remuzzi G, Dwyer J, et al. Early renin-angiotensin system intervention is more beneficial than late intervention in delaying end-stage renal disease in patients with type 2 diabetes. Diabetes Obes Metab. 2016;18:64–71. The study aims to develop and validate a model to simulate progression of diabetic kidney disease from early onset until end-stage renal disease, and to assess the effect of renin-angiotensin system intervention in early, intermediate and advanced stages of diabetic kidney disease.

    Article  PubMed  CAS  Google Scholar 

  47. Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, de Jong PE, et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med. 2003;139:244–52.

    Article  PubMed  CAS  Google Scholar 

  48. • Vejakama P, Ingsathit A, McKay GJ, Maxwell AP, McEvoy M, Attia J, et al. Treatment effects of renin-angiotensin aldosterone system blockade on kidney failure and mortality in chronic kidney disease patients. BMC Nephrol. 2017;18:342. The study aims to estimate the effectiveness of renin angiotensin aldosterone system (RAAS) blockade on CKD progression. Receiving RAAS blockade for 1 year or longer could prevent both CKD progression to ESRD and premature mortality.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000;160:685–93.

    Article  PubMed  CAS  Google Scholar 

  50. Hricik DE, Browning PJ, Kopelman R, Goorno WE, Madias NE, Dzau VJ. Captopril-induced functional renal insufficiency in patients with bilateral renal-artery stenoses or renal-artery stenosis in a solitary kidney. N Engl J Med. 1983;308:373–6.

    Article  PubMed  CAS  Google Scholar 

  51. Khosla N, Kalaitzidis R, Bakris GL. Predictors of hyperkalemia risk following hypertension control with aldosterone blockade. Am J Nephrol. 2009;30:418–24.

    Article  PubMed  CAS  Google Scholar 

  52. • Meaney CJ, Beccari MV, Yang Y, Zhao J. Systematic review and meta-analysis of patiromer and sodium zirconium cyclosilicate: a new armamentarium for the treatment of hyperkalemia. Pharmacotherapy. 2017;37:401–11. The systematic review and meta-analysis shows the efficacy and safety of patiromer and sodium zirconium cyclosilicate in the treatment of hyperkalemia.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Martinez-Martin FJ, Saiz-Satjes M. Add-on manidipine versus amlodipine in diabetic patients with hypertension and microalbuminuria: the AMANDHA study. Expert Rev Cardiovasc Ther. 2008;6:1347–55.

    Article  PubMed  CAS  Google Scholar 

  54. Ott C, Schneider MP, Raff U, Ritt M, Striepe K, Alberici M, et al. Effects of manidipine vs. amlodipine on intrarenal haemodynamics in patients with arterial hypertension. Br J Clin Pharmacol. 2013;75:129–35.

    Article  PubMed  CAS  Google Scholar 

  55. • Lin YC, Lin JW, Wu MS, Chen KC, Peng CC, Kang YN. Effects of calcium channel blockers comparing to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with hypertension and chronic kidney disease stage 3 to 5 and dialysis: a systematic review and meta-analysis. PLoS One. 2017;12:e0188975. The study shows that CCBs has similar effects on long term blood pressure, mortality, heart failure, stroke or cerebrovascular events, and renal function to RAAS blockades in patients CKD stage 3 to 5D and hypertension.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Bakris GL, Sarafidis PA, Weir MR, Dahlof B, Pitt B, Jamerson K, et al. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet. 2010;375:1173–81.

    Article  PubMed  CAS  Google Scholar 

  57. Kalaitzidis R, Bakris G. Should nephrologists use beta-blockers? A perspective. Nephrol Dial Transplant. 2009;24:701–2.

    Article  PubMed  Google Scholar 

  58. Briasoulis A, Oliva R, Kalaitzidis R, Flynn C, Lazich I, Schlaffer C, et al. Effects of nebivolol on aortic compliance in patients with diabetes and maximal renin angiotensin system blockade: the EFFORT study. J Clin Hypertens (Greenwich). 2013;15:473–9.

    Article  CAS  Google Scholar 

  59. Low-dose clonidine administration in the treatment of mild or moderate essential hypertension: results from a double-blind placebo-controlled study (Clobass). The Clobass Study Group. J Hypertens. 1990;8:539–46.

  60. Molvi SN, Mir S, Rana VS, Jabeen F, Malik AR. Role of antihypertensive therapy in mild to moderate pregnancy-induced hypertension: a prospective randomized study comparing labetalol with alpha methyldopa. Arch Gynecol Obstet. 2012;285:1553–62.

    Article  PubMed  CAS  Google Scholar 

  61. Fenton C, Keating GM, Lyseng-Williamson KA. Moxonidine: a review of its use in essential hypertension. Drugs. 2006;66:477–96.

    Article  PubMed  CAS  Google Scholar 

  62. Wilson C, Scott ME, Abdel-Mohsen A. Atenolol and methyldopa in the treatment of hypertension. Postgrad Med J. 1977;53(Suppl 3):123–7.

    PubMed  Google Scholar 

  63. Mathur RP, Nayak S, Sivaramakrishnan R, Jain V. Role of alpha blockers in hypertension with benign prostatic hyperplasia. J Assoc Physicians India. 2014;62:40–4.

    PubMed  CAS  Google Scholar 

  64. Vidt DG. Alpha-blockers and congestive heart failure: early termination of an arm of the ALLHAT trial. Cleve Clin J Med. 2000;67:429–33.

    Article  PubMed  CAS  Google Scholar 

  65. Gaynor MF, Wright GC, Vondracek S. Retrospective review of the use of as-needed hydralazine and labetalol for the treatment of acute hypertension in hospitalized medicine patients. Ther Adv Cardiovasc Dis. 2018;12:7–15.

    Article  PubMed  CAS  Google Scholar 

  66. Kandler MR, Mah GT, Tejani AM, Stabler SN, Salzwedel DM. Hydralazine for essential hypertension. Cochrane Database Syst Rev. 2011:CD004934.

  67. • Mundt HM, Matenaer M, Lammert A, Gottmann U, Kramer BK, Birck R, et al. Minoxidil for treatment of resistant hypertension in chronic kidney disease— retrospective cohort analysis. J Clin Hypertens.(Greenwich.). 2016;18:1162–7. The study shows that minoxidil as a reserve antihypertensive agent still has a niche indication in the particular subgroup of patients with treatment-resistant or uncontrolled hypertension.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology, University Hospital of Ioannina, 455 00, Ioannina, Greece

    Rigas G. Kalaitzidis

  2. Department of Internal Medicine, Medical School, University of Ioannina, 451 10, Ioannina, Greece

    Moses S. Elisaf

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  1. Rigas G. Kalaitzidis
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This article is part of the Topical Collection on Antihypertensive Agents: Mechanisms of Drug Action

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Kalaitzidis, R.G., Elisaf, M.S. Treatment of Hypertension in Chronic Kidney Disease. Curr Hypertens Rep 20, 64 (2018). https://doi.org/10.1007/s11906-018-0864-0

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