Discussion of these effects, which may be of relevance to renoprotection, is beyond the scope of this Guideline. Dose considerations in CKD patients. Most available ACE-Is have active moieties that are largely excreted in the urine. Fosinopril and trandolapril are partially (in general, approximately 50%) excreted by the liver, such that the blood levels are less influenced by kidney failure than levels of other ACE-Is which are predominantly excreted by the kidneys. Since ACE-Is are generally titrated to achieve optimal clinical effect, the mode of excretion is not regarded as a major factor If hyperkalemia occurs in CKD patients taking a renal excreted ACE-I, possible interventions include dietary advice, reducing the dose, switching to fosinopril or trandolapril, or adding a potassium-losing diuretic. All ARBs are substantially excreted by the liver, with the proportion of drug elimination ranging from 40% (in the case of candesartan) to 495% (in the case of irbesartan and telmisartan). As with ACE-Is, the dose in ARBs is usually adjusted according to clinical effect rather than kidney ACE-Is and ARBs should be used with caution or even avoided in certain CKD subgroups, particularly in patients with bilateral renal-artery stenosis or with intravas- cular fluid depletion, because of the risk of a large reduction in GFR. The normal capacity of the kidney to auto-regulate GFR in the face of fluctuations in BP is impaired in CKD and further compromised by the use of ACE-Is or ARBs. Hypotension (e.g.