Renin-Angiotensin Aldosterone System (RAAS)
The kidneys release renin, which acts on angiotensinogen (produced by the liver) to form angiotensin I. Angiotensin-converting enzyme (ACE) then converts angiotensin I into angiotensin II, which binds to two receptors — AT1R and AT2R.
Two drug classes are shown blocking this cascade (in blue):
ACE inhibitors (ACEI) block the conversion of angiotensin I to angiotensin II. This also prevents the breakdown of bradykinin into its inactive form.
Dosing recommendations for ACE inhibitors and ARBs according to the level of renal impairment.
Pharmacological drug
General drug dosing recommendations
Renal impairment drug dosing recommendations
Angiotensin-Converting Enzyme Inhibitors
.
Individualize dosing schedules for each HD session ot avoid intradialytic hypotension
Benazepril
Hyptension: 5-10 mg daily, titrate up to 40 mg daily
CrCl >30 ml/min: no adjustment
CrCl <30 ml/min: 5 mg daily; titrate up to 40 mg daily
HD/PD: 25-50% of usual dose; supplemental dose not necessary
Captopril
Diabetic Nephropathy: 25 mg TID
Hyptension: 12.5-25 mg BID or TID, titrate up to 50 mg TID
HFrEF: 6-25 mg TID, titrate up to 50 mg TID
LVD after MI: Single dose of 6.25 mg, then start at 12.5 mg TID, titrate up to 50 mg TID
Reduce initial daily dose and titrate slowly with smaller increments
CrCl >50 ml/min: no adjustment
CrCl 10-50 ml/min: 75% of normal dose every 12-18 h
CrCl < 10 ml/min: 50% of normal dose every 24 h
HD: administer after HD on HD days
PD: same as CrCl 10-50 ml/min as above
Enalapril
Hypertension: 5 mg daily, titrate up to 40 mg daily
HFrEF: 2.5 mg BID, titrate up to 10-20 mg BID
CrCl > 30 ml/min: no adjustment
CrCl < 30 mgl/min: 2.5 mg daily; titrate up to 40 mg daily
HD: 2.5 mg after HD on HD days, adjust dose on nondialysis days for goal BP
PD: adminster 25% of usual dose
Lisnopril
Hypertension: 5-10 mg daily, titrate up to 40 mg daily
HFrEF: 2.5-5 mg daily, titrate up to 40 mg daily
Reduction of mortality in acute MI: 2.5-5 mg daily within 24 h of presentation, titrate up to 10 mg, then slowly up to 40 mg daily
CrCl > 30 ml/min: no adjustment
CrCl 10-30 mgl/min: 2.5-5 mg daily(half of usual dose); titrate up to 40 mg daily
CrCl < 10 ml/min: 2.5 mg daily, titrate up to 40 mg daily
HD: 2.5 mg daily with dosing after HD, titrate up to 40 mg daily
CRRT: adminster 50-75% of usual dose
Ramipril
Hypertension: 2.5 mg daily, titrate up to 20 mg daily (or 10 mg BID)
LV dysfunction after MI: 1.25-2.5 mg BID, titrate up to 5 mg BID
Reduction in risk of MI, stroke, and CV death: 2.5 mg daily, titrate up to 10 mg.
CrCl > 40 ml/min: no adjustment
CrCl <40 mgl/min: 25% of usual dose
Angiotensin II Receptor Blockers
.
Levels of ARBs don't change significantly during HD
Candesartan
Hypertension: 2-8 mg daily, titrate up to 32 mg daily (16 mg BID)
HFrEF: 4-8 mg daily, titrate up to 32 mg daily
No adjustment necessary; however, not if CrCl < 30 ml/min, AUC and Cmax approximately doubled after repeated dosing
Irebesartan
Diabetic Nephropathy: 300 mg daily
Hypertension: 150 mg daily, titrate up to 300 mg daily
No adjustment necessary unless the patient is volume depleted (75 mg daily)
HD: non-dialyzable
Losartan
Diabetic Nephropathy: 50 mg daily, up to 100 mg daily
Hypertension: 25-50 mg daily, up to 100 mg daily
HFrEF: 25-50 mg daily, up to 150 mg daily
No adjustment necessary unless the patient is volume depleted (75 mg daily)
HD: non-dialyzable
Olmesartan
Hypertension: 20 mg daily, up to 40 mg daily
No adjustment necessary unless the patient is volume depleted (75 mg daily)
HD: non-dialyzable
Telmisartan
CV risk reduction: 80 mg daily
Hypertension: 20-40 mg daily, titrate up to 80 mg daily
No adjustments needed, but HD patients are at a greater risk for orthostatic hypotension.
Valsartan
Hypertension: 80-160 mg daily, titrate up to 320 mg daily
HFrEF: 40-80 mg BID, titrate up to 160 mg daily
LV dysfunction after MI: 20 mg BID, then increase to 40 mg BID, titrate up to 160 mg BID
CrCl > 30 ml/min: no adjustment
CrC < 30 ml/min: use with caution; no adjustment
HD: non-dialyzable
Mineralocorticoid receptor antagonist
.
Levels of ARBs don't change significantly during HD
Eplerenone
Hypertension: 50 mg daily, titrate up to 50 mg BID
(if concurrent use with moderate CYP3A4 inhibitors, then cut dose in half)
HFrEF: 40-80 mg BID, titrate up to 160 mg daily
LV dysfunction after MI: 25 mg daily, titrate up to 50 mg daily
CrCl > 50 ml/min: no adjustment
CrC 30-50ml/min, or sCr >2 mg/dl in males or >1.8 mg/dl in females: use not recommended due to risk of hyperkalemia
CrCl < 30 ml/min: contraindicated
HD: non-dialyzable
Spironolactone
Edema: 25-100 mg daily, titrate up to 200 mg daily
Hypertension: 25-50 mg daily, titrate up to 100 mg daily (or 50 mg bid)
HFrEF: 12.5-25 mg daily, titrate up to 50 mg daily
Hyperaldosteronism: 100-400 mg until surgical correction
Monitor for hyperkalemia; no adjustment for hypertension
HFrEF:
CrCl >50 ml/min: no adjustment
CrCl 30-50 ml/min: 25 mg EOD
CrCl <30 ml/min: not recommended
References
1) McCullough P, Ronco C. Textbook of Cardiorenal Medicine. 2021. doi:10.1007/978-3-030-57460-4