Chronic kidney disease (CKD) is defined as evidence of kidney damage that has lasted for three months or more.1 People with CKD are at risk of developing end-stage kidney disease and an even greater risk of developing subsequent cardiovascular events.2 Hypertension is estimated to be present in over 85% of people with CKD, so management of high blood pressure is an important component of care for people with CKD.3
The 2017 American College of Cardiology and American Heart Association (ACC/AHA) Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults recommends that people with CKD be treated with the usual first line medication choices, including hydrochlorothiazide (HCTZ).4 Reboussin et al. conducted a systematic review of 58 trials that compared the recommended first-line medications in the 2017 ACC/AHA guidelines and found that no class of medications (including angiotensin-converting enzyme inhibitors [ACE inhibitors], angiotensin receptor blockers [ARBs], calcium channel blockers [CCBs], or beta blockers) were significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any cardiovascular outcome.5
Physicians may check creatinine levels before prescribing HCTZ because it is metabolized more slowly in persons with kidney disease.6 The 2017 guidelines recommend that patients with albuminuria from CKD (≥300 mg/d or ≥300 mg/g creatinine) take an ACE inhibitor or an ARB. Similar recommendations have been made by other national and international organizations.4,7,8 There is strong evidence that use of these drugs that partially block the renin-angiotensin activating system of the kidney slows the progression of nephropathy in patients with advanced kidney disease.9
Ninomiya et al. conducted a meta-analysis of randomized controlled trials to determine the cardiovascular effects of different antihypertensives (ACE inhibitors, CCBs, diuretics, or beta blockers) used in people with CKD.10 They analyzed 26 studies including 30,295 people with CKD (estimated glomerular filtration rate [GFR] <60 mL/min/1.73 m2). Regardless of the choice of antihypertensive regimen, lowering systolic blood pressure by 5 mm Hg reduced the cardiovascular risk (myocardial infarction, stroke, heart failure, or cardiovascular mortality) by one-sixth. There was no evidence that the effects of different drug classes on major cardiovascular events varied between patients with different estimated GFR.
There is some evidence that patients with CKD and uncontrolled hypertension while taking renin-angiotensin system inhibitors may see renal benefits from adding HCTZ, but studies to date have been small.11–13
Hayashi et al. conducted a randomized open-label trial among patients with CKD and persistent hypertension while taking the ARB, losartan 50 mg. The goal of the study was to determine which added antihypertensives were most beneficial to these patients.12 Patients were randomly assigned to add either a CCB (amlodipine 5 mg, n=37), an ACE inhibitor (enalapril 5 mg, n=36), or a thiazide diuretic (HCTZ 12.5 mg, n=36). After 12 months of treatment, there was no significant difference among the groups with respect to tolerability of the medications or blood pressure control, but those taking HCTZ had a statistically significant percentage decrease in urinary excretion of protein to creatinine (26.3 ± 11.1%, p<0.05) compared to the ACE inhibitor and CCB cohorts.
- Sinha AD, Agarwal R. Thiazide diuretics in chronic kidney disease. Curr Hypertens Rep 2015; 17 (4).
- Taal M. Risk Factors and Chronic Kidney Disease. In: Brenner and Rector’s The Kidney. Elsevier Inc; 2016:669-692.
- Muntner P, Anderson A, Charleston J, et al. Hypertension awareness, treatment, and control in adults with CKD. Am J Kidney Dis 2010; 55 (3): 441-451.
- Whelton PK, Carey RM, Aronow WS, 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: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018; 71 (19): e127-e248.
- Reboussin DM, Allen NB, Griswold ME, et al. Systematic Review for the 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. Circulation 2018; 138 (17): e595-e616.
- Hydrochlorothiazide [package Insert]. Morgantown, WV: Mylan Pharmaceuticals; 2011.
- K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kid Dis 2004; 43 (5 Suppl 1): S1-290.
- Becker G, Wheeler D, DeZeeuw D, Fujita T, Holdas F et al. 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): 2012.
- Elliott W, Peixoto A, Bakris G. Primary and Secondary Hypertension. In: Brenner and Rector’s The Kidney. ; 2016:1522-1566.
- Ninomiya T, Perkovic V, Turnbull F, et al. Blood pressure lowering and major cardiovascular events in people with and without chronic kidney disease: meta-analysis of randomised controlled trials. BMJ 2013; 347 : f5680.
- Fujisaki K, Tsuruya K, Nakano T, et al. Impact of combined losartan/hydrochlorothiazide on proteinuria in patients with chronic kidney disease and hypertension. Hypertens Res 2014; 37 (11): 993-998.
- Hayashi M, Uchida S, Kawamura T, Kuwahara M, Nangaku M, Iino Y. Prospective randomized study of the tolerability and efficacy of combination therapy for hypertensive chronic kidney disease: results of the PROTECT-CKD study. Clin Exp Nephrol 2015; 19 (5): 925-932.
- Karadsheh F, Weir MR. Thiazide and thiazide-like diuretics: an opportunity to reduce blood pressure in patients with advanced kidney disease. Curr Hypertens Rep 2012; 14 (5): 416-420.