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301

counteracted with diuretics. Non-dihydropyridines should not be associated with
BBs, because of risks of bradycardia and depression of myocardial inotropism.
MR antagonists may be used as fourth-line therapy for RH in patients with GFR
≥30 ml/min and plasma potassium concentrations ≤4–5 mmol/L or in patients with
other indications, such as heart failure. However, they should be used with caution
in CKD patients, particularly in combination with ACEIs or ARBs, because of
increased risk of hyperkalemia and acute kidney injury. Although, these drugs were
shown to be very effective in patients with essential RH, the long-term effects of
MR antagonists on renal and cardiovascular outcomes, mortality, and safety in
patients with CKD are still to be determined.
BBs have been widely used for decades to treat hypertension, as well as coronary
artery disease, heart failure, and cardiac arrhythmias. Adverse effects associated
with BBs include bradycardia, erectile dysfunction, fatigue, and lipid and glucose
abnormalities. Agents like metoprolol and carvedilol should be preferred over aten-
olol, which may accumulate in patients with CKD.
Other fourth- or fifth-line antihypertensive agents include centrally acting alpha-
agonists, alpha-blockers, and direct vasodilators. They are potent BP-lowering
drugs and do not require dose adjustments in CKD (except for moxonidine).
However, their use is limited by numerous side effects; among these, fluid retention
usually requires the association with diuretics.

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