In addition, because CKD patients are at higher risk of side effects, particularly hyperkalemia and reduction in GFR, the use of ACE-Is or ARBs may not have the same risk-to-benefit ratio in CKD patients as in non-CKD populations. Drug combinations. The antihypertensive and anti- albuminuric effects of ACE-Is and ARBs are complemented by dietary sodium restriction or administration of diure- ACE-Is and ARBs are therefore valuable adjuncts to diuretics for the treatment of high BP and vice versa. Co- administration of beta-blockers and calcium-channel block- ers with ACE-Is or ARBs is also acceptable. One recent post hoc analysis of a large trial involving hypertensive individuals demonstrated that a combination of an ACE-I (benazepril) and calcium antagonist (amlodipine) was superior to the same ACE-I used with a diuretic (hydrochlorothiazide) in slowing CKD progression.101 Patients given NSAIDs, COX-2 antagonists or potassium- sparing diuretics can develop hyperkalemia if these drugs are used in combination with ACE-Is or ARBs. The combination of ACE-Is and/or ARBs with aldosterone-blocking antago- nists is an area of current controversy that is covered in more detail below and in Chapter 8. Aldosterone antagonists. The aldosterone antagonist spiro- lactone has been in use as a BP-lowering agent since the late 1950s. Prescribed as a diuretic in the treatment of edema and resistant hypertension, it fell into disuse with the advent of more powerful diuretics and antihypertensives. With the high doses initially used (up to 300 mg/day), spironolactone use was associated with side effects, particularly those due to its estrogen-like activity (gynecomastia and menstrual distur- bances). Recognition that BP-lowering could be achieved with much lower doses of spironolactone (12.5 50 mg/day) has led to renewed interest in aldosterone antagonists over the past decade.102 105 As a result, eplerenone, a miner- alocorticoid-receptor blocker without estrogen-like effects, has been developed. 