299Other Agents
Alpha-blockers are seldom used in dialysis patients. However, in those requiring multiple
antihypertensive agents, they can be safely prescribed and do not require additional dos-
ing after HD. Nocturnal administration is preferred, in order to prevent postural hypoten-
sion. These agents should be avoided in patients with intradialytic hypotension [ 47 ].
Centrally acting alpha-adrenergic agonists are also rarely used, because of their
high rate of adverse side effects. However, they may still be useful in dialysis
patients, particularly those with RH [ 47 ].
Hydralazine and minoxidil are potent vasodilators and can be effective in dialy-
sis patients with RH. These drugs are not removed by HD. Because of reflex stimu-
lation of the sympathetic nervous system, they should be administered together with
a BB. Fluid retention, including pleural and pericardial effusions, may occur during
therapy and may require drug discontinuation [ 47 ].
New Antihypertensive Agents for CKD Patients
Phosphodiesterase Type 5 (PDE5) Inhibitors
In CKD, relative deficiency of circulating nitric oxide (NO) may contribute to
hypertension and atherosclerosis, whereas NO deficiency within the kidneys may
promote a sharper decline in renal function. Abundant PDE5 expression has been
identified in the kidney, and, therefore, it has been proposed that, through its inhibi-
tion, the function of the renal NO-cGMP pathway in the kidney can be enhanced,
improving the NO deficit associated with CKD. The benefits of PDE5 inhibitors
may extend from BP-lowering effects to renoprotective properties [ 71 ]. Experimental
studies have demonstrated favorable effects of PDE5 inhibition on mesangial cell
proliferation, extracellular matrix expansion, tubulointerstitial injury, renal cell
apoptosis, oxidative stress, inflammation, and proteinuria in CKD models [ 71 ].
To date, only one clinical trial of PDE5 inhibition in CKD has been published
[ 72 ]. In this study, 40 men with type 2 diabetes mellitus were treated for 1 month
with either 50 mg sildenafil daily or placebo. The sildenafil-treated group had a 50%
reduction in albuminuria and the drug was well tolerated. A randomized, placebo-
controlled trial is currently investigating the impact of a long-acting PDE5 inhibitor
on patients with diabetes mellitus and overt nephropathy [ 71 ].
Endothelin Antagonists
Endothelin-1 (ET-1) upregulation plays a pathogenic role in endothelial dysfunction
and atherosclerosis and may also contribute to cardiovascular complications of
CKD [ 71 ]. Selective endothelin type A (ETA) receptor antagonist darusentan, but
18 Treatment of Hypertension in Light of the New Guidelines: Pharmacologic...