Management of Hypertension in Chronic Kidney Disease

Antihypertensive Therapy

The European Society of Cardiology recommends first-line antihypertensive therapy with an ACE inhibitor or ARB, combined with a loop diuretic if needed, targeting a systolic blood pressure of 120-129 mmHg for patients with moderate chronic kidney disease (eGFR 39) 1
ACE inhibitors or ARBs reduce albuminuria and provide cardiovascular protection, and should be used as first-line agents for patients with eGFR <30 ml/min per 1.73 m² 2, 3
Consider adding an SGLT2 inhibitor for patients with eGFR >20 mL/min/1.73 m² to improve outcomes, which provide modest BP-lowering effects with additional renal and cardiovascular benefits 1

Loop diuretics are preferred over thiazides when eGFR <30 ml/min/1.73m², and may still be effective for volume control in patients with eGFR just above this threshold 2
For patients with chronic kidney disease, loop diuretics should be considered instead of thiazide diuretics, and renal function and electrolytes should be monitored closely, especially when using RAS blockers, as recommended by the American College of Physicians and the American Heart Association 4, 5

The European Society of Cardiology recommends a target systolic BP of 120-129 mmHg (if tolerated) to reduce cardiovascular risk in patients with moderate-to-severe CKD and eGFR >30 mL/min/1.73 m² 1
Blood pressure should be checked with every clinic visit, which should be at least every three months, and consider home BP monitoring to ensure adequate control 3
The American College of Cardiology recommends checking BP within 1 month of medication changes and monitoring electrolytes and renal function 1-2 weeks after initiation of RAS blockers or diuretics, and schedule follow-up at least every 3-6 months once BP is controlled 6

Resistant hypertension is defined as blood pressure ≥130/80 mmHg despite adherence to 3 or more antihypertensive agents from different classes at optimal doses, including a diuretic, or blood pressure controlled but requiring 4 or more medications, as defined by the American College of Physicians and the American Heart Association 4, 7, 8, 9, 10, 11, 2

The following secondary causes of resistant hypertension have the following prevalence:

Secondary Cause	Prevalence
Primary aldosteronism	10-20%
Sleep apnea	High prevalence
Chronic kidney disease	Volume overload, increased sympathetic activity, and RAAS activation
Renal artery stenosis	High-risk group including peripheral arterial disease and unexplained renal insufficiency
Pheochromocytoma	Less than 1%
Cushing's syndrome	Less than 1%
Hyperthyroidism and hypothyroidism	1-2%
Aortic coarctation	Less than 1%

The American College of Physicians recommends that patients with resistant hypertension should be on optimal doses of a three-drug regimen including an ACE inhibitor or ARB, a long-acting calcium channel blocker, and a thiazide-like diuretic, preferably chlorthalidone or indapamide instead of hydrochlorothiazide 4
Initial therapy should start with a single agent or combination of ACE inhibitor/ARB + CCB or diuretic, with the option to increase to triple therapy with ACE inhibitor/ARB + CCB + thiazide-like diuretic if BP is not controlled after 1-3 months, as recommended by the American College of Cardiology and the European Society of Cardiology 6, 1
Consider beta-blockers if heart rate is not <70 beats/min 9
Add hydralazine (starting at 25 mg three times daily and titrating upward) as a fifth step in treatment, and substitute minoxidil for hydralazine (starting at 2.5 mg two to three times daily) as a sixth step in treatment 9
Spironolactone is the preferred fourth agent, with a dose of 25-50 mg daily, as recommended by the American Heart Association and the European Society of Cardiology, and alternatives to spironolactone, including eplerenone, amiloride, doxazosin, and beta-blockers, are recommended by the American College of Cardiology and the European Society of Cardiology 12, 1, 11

Essential adjuncts to pharmacotherapy include dietary sodium restriction (<2,300 mg/day), DASH diet implementation, weight loss if overweight/obese, regular physical activity, alcohol limitation, adequate sleep (≥6 hours uninterrupted), and discontinuation of interfering substances, as recommended by the American Diabetes Association, American Heart Association, and the European Society of Cardiology 7, 10, 9, 4, 13, 1
Increasing fluid intake to target urine volume >2.5 L/day and dietary sodium restriction (<2300 mg/day) is recommended for both hypertension and stone prevention, as recommended by the American Urological Association 14

Monitor serum potassium and renal function within 1-2 weeks of starting spironolactone, and closely when adding spironolactone to ARB therapy due to increased risk of hyperkalemia, as recommended by the American Heart Association and the American College of Cardiology, and consider referral to a hypertension specialist for further evaluation if BP remains uncontrolled after adding spironolactone 9, 2
Monitor nutritional status by measuring body weight and serum albumin every three months 3
Test for orthostatic hypotension before starting or intensifying BP-lowering medication, and measure BP after 5 minutes of sitting/lying and then 1-3 minutes after standing 1

Resistant hypertension is associated with a 2-6 fold higher risk for myocardial infarction, stroke, end-stage renal disease, and death compared to non-resistant hypertension, making aggressive management essential to reduce cardiovascular morbidity and mortality, as stated by the American College of Physicians 4
Patients with hemodynamically significant renal artery stenosis may present with accelerated hypertension, resistant hypertension, malignant hypertension, hypertension with unexplained unilateral small kidney, or hypertension with medication intolerance, as recommended by the American Heart Association 15
Renal denervation is not a first-line BP-lowering intervention for hypertension, as stated in the 2024 ESC guidelines, and should only be considered for patients with resistant hypertension, with variant renal anatomy, such as dual right renal arteries, increasing procedural complexity and potential risks of renal denervation, and should be evaluated before considering the procedure, as noted by the American Heart Association and the European Society of Cardiology 1, 16