Hypertension remains an important cause of morbidity and mortality in patients with chronic kidney disease. It both contributes to and is a consequence of chronic renal dysfunction. There is a high prevalence of hypertension in chronic kidney disease, and rates of control remain sub-optimal. Numerous studies have highlighted the benefit of treating hypertension in reducing the overall mortality as well as progression of renal disease in this population. Non-pharmacologic treatment strategies remain the primary intervention in all patients but are insufficient on their own to control hypertension in most cases. Pharmacologic treatment recommendations, however, vary depending on the specific etiology of disease as well as patient characteristics. Though most classes of anti-hypertensive drugs can be used to lower blood pressure in chronic kidney disease, therapy needs to be selected based on the presence of specific co-morbidities as well as the etiology of the kidney disease. Most patients will require multi-drug therapy for achieving target blood pressure goals. This review discusses the pharmacologic options in management of hypertension in various forms of chronic kidney disease.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Ridao N, Luno J, Garcia de Vinuesa S, et al. Prevalence of hypertension in renal disease. Nephrol Dial Transplant. 2001;16:70–3.
Muntner P, Anderson A, Charleston J, 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.
Hsu CY, McCulloch CE, Darbinian J, et al. Elevated blood pressure and risk of end-stage renal disease in subjects without baseline kidney disease. Arch Intern Med. 2005;165(8):923–8.
Gu Q, Burt VL, Dillon CF, et al. Trends in antihypertensive medication use and blood pressure control among United States adults with hypertension: the national health and nutrition examination survey, 2001 to 2010. Circulation. 2012;126(17):2105–14.
Ostchega Y, Dillon CF, Hughes JP, et al. Trends in hypertension prevalence, awareness, treatment, and control in older U.S. adults: data from the National Health and Nutrition Examination Survey 1988 to 2004. J Am Geriatr Soc. 2007;55(7):1056–65.
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(13):1296–305.
Anavekar NS, McMurray JJ, Velazquez EJ, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004;351(13):1285–95.
Tozawa M, Iseki K, Iseki C, et al. Blood pressure predicts risk of developing end-stage renal disease in men and women. Hypertension. 2003;41(6):1341–5.
Tonelli M, Muntner P, Lloyd A, et al. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet. 2012;380(9844):807–14.
Hemmelgarn BR, Manns BJ, Lloyd A, et al. Relation between kidney function, proteinuria, and adverse outcomes. JAMA. 2010;303(5):423–9.
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(8):629–36.
Perkovic V, Ninomiya T, Arima H, et al. Chronic kidney disease, cardiovascular events, and the effects of perindopril-based blood pressure lowering: data from the PROGRESS study. J Am Soc Nephrol: JASN. 2007;18(10):2766–72.
Solomon SD, Rice MM, Jablonski AJ, et al. Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial. Circulation. 2006;114(1):26–31.
Strazzullo P, Galletti F, Barba G. Altered renal handling of sodium in human hypertension: short review of the evidence. Hypertension. 2003;41(5):1000–5.
Salem MM. Pathophysiology of hypertension in renal failure. Semin Nephrol. 2002;22(1):17–26.
Blaustein MP, Leenen FH, Chen L, et al. How NaCl raises blood pressure: a new paradigm for the pathogenesis of salt-dependent hypertension. Am J Physiol Heart Circ Physiol. 2012;302(5):H1031–49.
Vasavada N, Agarwal R. Role of excess volume in the pathophysiology of hypertension in chronic kidney disease. Kidney Int. 2003;64(5):1772–9.
Agarwal R, Alborzi P, Satyan S, et al. Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized, controlled trial. Hypertension. 2009;53(3):500–7.
Weidmann P, Maxwell MH, Lupu AN, et al. Plasma renin activity and blood pressure in terminal renal failure. N Engl J Med. 1971;285(14):757–62.
Palmer BF. Renal dysfunction complicating the treatment of hypertension. N Engl J Med. 2002;347(16):1256–61.
Apperloo AJ, de Zeeuw D, de Jong PE. A short-term antihypertensive treatment-induced fall in glomerular filtration rate predicts long-term stability of renal function. Kidney Int. 1997;51(3):793–7.
Tinucci T, Abrahao SB, Santello JL, et al. Mild chronic renal insufficiency induces sympathetic overactivity. J Hum Hypertens. 2001;15(6):401–6.
Converse RL Jr, Jacobsen TN, Toto RD, et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992;327(27):1912–8.
Klein IH, Ligtenberg G, Oey PL, et al. Sympathetic activity is increased in polycystic kidney disease and is associated with hypertension. J Am Soc Nephrol: JASN. 2001;12(11):2427–33.
Hausberg M, Kosch M, Harmelink P, et al. Sympathetic nerve activity in end-stage renal disease. Circulation. 2002;106(15):1974–9.
Klein IH, Ligtenberg G, Oey PL, et al. Enalapril and losartan reduce sympathetic hyperactivity in patients with chronic renal failure. J Am Soc Nephrol. 2003;14(2):425–30.
Schlaich MP, Socratous F, Hennebry S, et al. Sympathetic activation in chronic renal failure. J Am Soc Nephrol: JASN. 2009;20(5):933–9.
Symplicity HTNI, Esler MD, Krum H, 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.
Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373(9671):1275–81.
Ott C, Schmid A, Ditting T, et al. Renal denervation in a hypertensive patient with end-stage renal disease and small arteries: a direction for future research. J Clin Hypertens. 2012;14(11):799–801.
Hering D, Mahfoud F, Walton AS, et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012;23(7):1250–7.
Shultz PJ. An emerging role for endothelin in renal disease. J Lab Clin Med. 1992;119(5):448–9.
Campese VM, Mitra N, Sandee D. Hypertension in renal parenchymal disease: why is it so resistant to treatment? Kidney Int. 2006;69(6):967–73.
Zoccali C. Endothelial dysfunction in CKD: a new player in town? Nephrol Dial Transplant. 2008;23(3):783–5.
Weber MA, Black H, Bakris G, 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(9699):1423–31.
Zoccali C, Mallamaci F, Tripepi G. Sleep apnea in renal patients. J Am Soc Nephrol. 2001;12(12):2854–9.
Ficker JH, Dertinger SH, Siegfried W, et al. Obstructive sleep apnoea and diabetes mellitus: the role of cardiovascular autonomic neuropathy. Eur Resp J. 1998;11(1):14–9.
Logan AG, Perlikowski SM, Mente A, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001;19(12):2271–7.
Sim JJ, Rasgon SA, Derose SF. Sleep apnea and hypertension: prevalence in chronic kidney disease. J Clin Hypertens. 2007;9(11):837–41.
Phillips BG, Somers VK. Hypertension and obstructive sleep apnea. Curr Hypertens Rep. 2003;5(5):380–5.
Yumino D, Redolfi S, Ruttanaumpawan P, et al. Nocturnal rostral fluid shift: a unifying concept for the pathogenesis of obstructive and central sleep apnea in men with heart failure. Circulation. 2010;121(14):1598–605.
Hanly PJ, Pierratos A. Improvement of sleep apnea in patients with chronic renal failure who undergo nocturnal hemodialysis. N Engl J Med. 2001;344(2):102–7.
Tang SC, Lam B, Ku PP, et al. Alleviation of sleep apnea in patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis. J Am Soc Nephrol. 2006;17(9):2607–16.
Pressman MR, Benz RL, Schleifer CR, et al. Sleep disordered breathing in ESRD: acute beneficial effects of treatment with nasal continuous positive airway pressure. Kidney Int. 1993;43(5):1134–9.
Hricik DE, Lautman J, Bartucci MR, et al. Variable effects of steroid withdrawal on blood pressure reduction in cyclosporine-treated renal transplant recipients. Transplantation. 1992;53(6):1232–5.
Institute of Medicine (U.S.). Committee on Strategies to Reduce Sodium Intake., Henney JE, Taylor CL, et al. Strategies to reduce sodium intake in the United States. National Academies Press, Washington, DC; 2010.
Rabi DM, Daskalopoulou SS, Padwal RS, et al. The 2011 Canadian Hypertension Education Program recommendations for the management of hypertension: blood pressure measurement, diagnosis, assessment of risk, and therapy. Can J Cardiol. 2011;27(4):415–33 e1–2.
Appel LJ, Espeland MA, Easter L, et al. Effects of reduced sodium intake on hypertension control in older individuals: results from the Trial of Nonpharmacologic Interventions in the Elderly (TONE). Arch Intern Med. 2001;161(5):685–93.
Boudville N, Ward S, Benaroia M, et al. Increased sodium intake correlates with greater use of antihypertensive agents by subjects with chronic kidney disease. Am J Hypertens. 2005;18(10):1300–5.
Pimenta E, Gaddam KK, Oparil S, et al. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Hypertension. 2009;54(3):475–81.
Van Hoogdalem P, Donker AJ, Leenen FH. Angiotensin II blockade before and after marked sodium depletion in patients with hypertension. Clin Sci Mol Med. 1978;54(1):75–83.
Heeg JE, de Jong PE, van der Hem GK, et al. Efficacy and variability of the antiproteinuric effect of ACE inhibition by lisinopril. Kidney Int. 1989;36(2):272–9.
Carter BL. Dosing of antihypertensive medications in patients with renal insufficiency. J Clin Pharmacol. 1995;35(1):81–6.
Kappel J, Calissi P. Nephrology: 3. Safe drug prescribing for patients with renal insufficiency. CMAJ. 2002;166(4):473–7.
Barreras A, Gurk-Turner C. Angiotensin II receptor blockers. Proc (Bayl Univ Med Cent). 2003;16(1):123–6.
Portaluppi F, Montanari L, Massari M, et al. Loss of nocturnal decline of blood pressure in hypertension due to chronic renal failure. Am J Hypertens. 1991;4(1 Pt 1):20–6.
Minutolo R, Agarwal R, Borrelli S, et al. Prognostic role of ambulatory blood pressure measurement in patients with nondialysis chronic kidney disease. Arch Intern Med. 2011;171(12):1090–8.
Pogue V, Rahman M, Lipkowitz M, et al. Disparate estimates of hypertension control from ambulatory and clinic blood pressure measurements in hypertensive kidney disease. Hypertension. 2009;53(1):20–7.
Zannad F, Matzinger A, Larche J. Trough/peak ratios of once daily angiotensin converting enzyme inhibitors and calcium antagonists. Am J Hypertens. 1996;9(7):633–43.
Hermida RC, Ayala DE, Mojon A, et al. Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD. J Am Soc Nephrol. 2011;22(12):2313–21.
Wolf G, Ritz E. Diabetic nephropathy in type 2 diabetes prevention and patient management. J Am Soc Nephrol: JASN. 2003;14(5):1396–405.
Bakris GL, Williams M, Dworkin L, 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(3):646–61.
Hermida RC, Ayala DE, Mojon A, et al. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010;27(8):1629–51.
Hoshide S, Kario K, Hoshide Y, et al. Associations between nondipping of nocturnal blood pressure decrease and cardiovascular target organ damage in strictly selected community-dwelling normotensives. Am J Hypertens. 2003;16(6):434–8.
Brater DC. Diuretic therapy. N Engl J Med. 1998;339(6):387–95.
Hughes AD. How do thiazide and thiazide-like diuretics lower blood pressure. J Renin Angiotensin Aldosterone Syst. 2004;5(4):155–60.
Acchiardo SR, Skoutakis VA. Clinical efficacy, safety, and pharmacokinetics of indapamide in renal impairment. Am Heart J. 1983;106(1 Pt 2):237–44.
Holland OB, Gomez-Sanchez CE, Kuhnert LV, et al. Antihypertensive comparison of furosemide with hydrochlorothiazide for black patients. Arch Intern Med. 1979;139(9):1015–21.
Ram CV, Garrett BN, Kaplan NM. Moderate sodium restriction and various diuretics in the treatment of hypertension. Arch Intern Med. 1981;141(8):1015–9.
Bank N, Lief PD, Piczon O. Use of diuretics in treatment of hypertension secondary to renal disease. Arch Intern Med. 1978;138(10):1524–9.
Kidney Disease Outcomes Quality I. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 Suppl 1):S1–290.
Dargie HJ, Allison ME, Kennedy AC, et al. Efficacy of metolazone in patients with renal edema. Clin Nephrol. 1974;2(4):157–60.
Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23):2417–28.
Ruggenenti P, Perna A, Loriga G, et al. Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial. Lancet. 2005;365(9463):939–46.
Chapman N, Dobson J, Wilson S, et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007;49(4):839–45.
Heshka J, Ruzicka M, Hiremath S, et al. Spironolactone for difficult to control hypertension in chronic kidney disease: an analysis of safety and efficacy. J Am Soc Hypertens: JASH. 2010;4(6):295–301.
Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006;70(12):2116–23.
Investigators O, Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59.
Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012;367(23):2204–13.
Feldman RD, Campbell N, Larochelle P, et al. 1999 Canadian recommendations for the management of hypertension. Task Force for the Development of the 1999 Canadian Recommendations for the Management of Hypertension. CMAJ. 1999;161 Suppl 12:S1–17.
Klag MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med. 1996;334(1):13–8.
Jafar TH, Stark PC, Schmid CH, 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(4):244–52.
Weiner DE, Tighiouart H, Amin MG, et al. Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol: JASN. 2004;15(5):1307–15.
Wright JT Jr, Bakris G, Greene T, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the trial. JAMA. 2002;288(19):2421–31.
Klahr S, Levey AS, Beck GJ, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. 1994;330(13):877–84.
Peterson JC, Adler S, Burkart JM, 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(10):754–62.
Appel LJ, Wright JT Jr, Greene T, et al. Intensive blood-pressure control in hypertensive chronic kidney disease. N Engl J Med. 2010;363(10):918–29.
Upadhyay A, Earley A, Haynes SM, et al. Systematic review: blood pressure target in chronic kidney disease and proteinuria as an effect modifier. Ann Intern Med. 2011;154(8):541–8.
Daskalopoulou SS, Khan NA, Quinn RR, et al. The 2012 Canadian hypertension education program recommendations for the management of hypertension: blood pressure measurement, diagnosis, assessment of risk, and therapy. Can J Cardiol. 2012;28(3):270–87.
Officers A. Coordinators for the ACRGTA, Lipid-Lowering Treatment to Prevent Heart Attack T. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981–97.
Ruggenenti P, Remuzzi G, Tognoni G, et al., for the GISEN Group. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet. 1997;349(9069):1857–63.
Turner R, Holman R, Stratton I, et al., for the UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):703–13.
Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998;351(9118):1755–62.
Ruilope LM, Salvetti A, Jamerson K, et al. Renal function and intensive lowering of blood pressure in hypertensive participants of the hypertension optimal treatment (HOT) study. J Am Soc Nephrol. 2001;12(2):218–25.
Schrier RW, Estacio RO, Esler A, et al. Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int. 2002;61(3):1086–97.
Group AS, Cushman WC, Evans GW, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575–85.
Fox KM. Investigators EUtOrocewPiscAd. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362(9386):782–8.
Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.
Lewis EJ, Hunsicker LG, Clarke WR, 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(12):851–60.
Berl T, Hunsicker LG, Lewis JB, et al. Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial. J Am Soc Nephrol. 2005;16(7):2170–9.
Pohl MA, Blumenthal S, Cordonnier DJ, et al. Independent and additive impact of blood pressure control and angiotensin II receptor blockade on renal outcomes in the irbesartan diabetic nephropathy trial: clinical implications and limitations. J Am Soc Nephrol. 2005;16(10):3027–37.
Coomer RW, Schulman G, Breyer JA, et al. Ambulatory blood pressure monitoring in dialysis patients and estimation of mean interdialytic blood pressure. Am J Kidney Dis. 1997;29(5):678–84.
Alborzi P, Patel N, Agarwal R. Home blood pressures are of greater prognostic value than hemodialysis unit recordings. Clin J Am Soc Nephrol. 2007;2(6):1228–34.
Zager PG, Nikolic J, Brown RH, et al. “U” curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc. Kidney Int. 1998;54(2):561–9.
Jindal K, Chan CT, Deziel C, et al. Hemodialysis clinical practice guidelines for the Canadian Society of Nephrology. J Am Soc Nephrol. 2006;17(3 Suppl 1):S1–27.
Locatelli F, Covic A, Chazot C, et al. Hypertension and cardiovascular risk assessment in dialysis patients. Nephrol Dial Transplant. 2004;19(5):1058–68.
Tentori F, Hunt WC, Rohrscheib M, et al. Which targets in clinical practice guidelines are associated with improved survival in a large dialysis organization? J Am Soc Nephrol. 2007;18(8):2377–84.
Cannella G, Paoletti E, Delfino R, et al. Prolonged therapy with ACE inhibitors induces a regression of left ventricular hypertrophy of dialyzed uremic patients independently from hypotensive effects. Am J Kidney Dis. 1997;30(5):659–64.
Zannad F, Kessler M, Lehert P, et al. Prevention of cardiovascular events in end-stage renal disease: results of a randomized trial of fosinopril and implications for future studies. Kidney Int. 2006;70(7):1318–24.
Hemodialysis Adequacy Work G. Clinical practice guidelines for hemodialysis adequacy, update 2006. Am J Kidney Dis. 2006;48 Suppl 1:S2–90.
Cice G, Ferrara L, D’Andrea A, et al. Carvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial. J Am Coll Cardiol. 2003;41(9):1438–44.
Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887–98.
None of the authors have any relevant conflicts of interest to report.
About this article
Cite this article
Talreja, H., Ruzicka, M. & McCormick, B.B. Pharmacologic Treatment of Hypertension in Patients With Chronic Kidney Disease. Am J Cardiovasc Drugs 13, 177–188 (2013). https://doi.org/10.1007/s40256-013-0009-4
- Chronic Kidney Disease
- Resistant Hypertension
- Advanced Chronic Kidney Disease
- Central Sympathetic Outflow