Antihypertensives in Renally Impaired Patients

Beta-blockers
Patients with renal disease respond well to beta-blockers. The choice of drug would be a cardioselective, hepatically excreted drug like metoprolol. However, atenolol, which is renally excreted, can eb given safely if introduced at low doses.


ACE inhibitors
ACE inhibitors are often useful since hypertension can be caused by activation of the renin-angiotensin system. However, renal function should be closely monintored in pre-dialysis pateitns when these drugs are introduced as they are contraindicated in patients with renal artery stenosis.

Do note that in conditions of decreased renal perfusion, the desirable effects will be efferent arteriolar vasocontriction to increase intraglomerular hydrostatic pressure and maintain ultrafiltrate production. Another effect will be afferent arteriolar vasodilatation to improve blood flow to the glomerulus. ACE inhibitors are efferent arteriolar vasodilators, hence they can increase the rate of decline of renal function. However, this can be used to advantage in patients with diabetes, where a reduction in hyperfiltration can delay the progression of diabetic nephropathy.

ACE inhibitors are renally excreted (ramipril is also partially hepatically excreted) and the half-life of these drugs is increased in renally impaired patients, hence they should be used with caution. Also, they can cause an increase in potassium levels.


Angiotensin II Receptor Blockers (ARBs)
ARBs can be beneficial in patients with chronic kidney disease since they block the effects of angiotensin II (a vasoconstrictor), causing vasodilation. As with ACEi, renal function should be closely monitored. They can also be useful when used in combination with an ACEi.


Calcium Channels Blockers (CCBs)
CCBs can be used safely in patients with chronic renal failure. However, one of the side effects of this group, especially of nifedipine, is ankle swelling and unresponsive to diuretics, which can be mistaken for fluid overland.

Ankle swelling is less of a problem with longer-acting agents, such as amlodipine.


Vasodilators
These include doxazocin, prazosin, hydralazine and minoxidil, all of which are hepatically metabolised. They are usually added when other drugs are ineffective. Minoxidil is best given with a beta-blocker and a diuretic, since it can cause tachycardia and fluid retention.


Summary
If BP > 130/80 mmHg: (proceed to next step if BP still not at goal)

1. Start ACEi or ARB
Check serum creatinine & potassium in 1 week; if SrCr or K increases by > 30%, discontinue
agent.

2. Add diuretics
CrCL > or = 30 mL/min: thiazide diuretic
Cr CL <>calcium channel blocker
May consider adding low-dose beta blocker instead of CCB if patient has angina, heart failure
or arrhythmia necessitating their use.

4. Baseline pulse > or = 84: low-dose beta blocker OR alpha/beta blocker (if not already in use)
Baseline pulse < style="color: rgb(51, 51, 255);">subgroup of CCB (e.g. a dihydropyridine if a
non-dihydropyridine is in use)
Note: the use of beta blcoker and a non-dihydropyridine CCB should be avoided in the
elderly and those with conduction abnormalities.

5. Add long-acting alpha blocker, central alpha agonist, OR vasodilator.
Note: Central alpha agonists (i.e. clonidine) should not be used with beta blockers due to the
high likelihood of severe bradycardia.


References:
1. Wells BG, Dipiro JT, Schwinghammer TL and Hamilton CW. Pharmacotherapy handbook. USA: The McGraw-Hills Company; 2006.

2. Morlidge C. Managing chronic renal disease. The Pharmaceutical Journal 2001; 266: 655-657.