There have been no RCTs assessing hard renal or cardio- vascular outcomes, in which patients have been randomized to different targets of urinary albumin excretion irrespective of BP. 8.4: SHOULD RAAS INHIBITION BE MAXIMIZED IN CKD PATIENTS? Accepting that RAAS inhibitors may be used to both lower BP and urine albumin excretion, options are available to optimize the albuminuria lowering effect of these agents. For example, it is well recognized that co-administration of a low-sodium or the addition of a diuretic63,66,419 enhances the effect of both ACE-Is and ARBs on lowering urine albumin excretion. Such therapeutic combinations make good sense and are unlikely to be associated with harmful side effects. Whether more aggressive blockade of the RAAS using supramaximal doses of ACE-Is or ARBs is beneficial is less certain. Recently, Burgess et al.420 showed that increasing the dose of candesartan well beyond the guideline-recommended dose for BP-lowering resulted in further reduction of the urine albumin levels. The substantial evidence suggesting that RAAS inhibition using ACE-Is or ARBs has renoprotective effects when these agents are used individually has led to the hypothesis that combining the two classes of agents, or adding an aldosterone antagonist or a DRI, may provide additional benefit. Interest in this approach has been increased by the evidence that individuals treated with ACE-Is may have aldosterone breakthrough 89 with angiotensin I to angiotensin II conversion occurring via other and by the fact that there may be other active receptors for angiotensin II422 that may have a range of roles. 