Other information of value in deciding on the optimal BP lowering regimen include data on drug half-life and dose adjustments in CKD stage 5D, which may be of help in guiding the use of BP lowering drugs in advanced CKD ND.4,76 The optimal timing of administration of medication has not been studied in CKD patients. CKD patients who do not have the normal decrease in BP during sleep (non-dippers and reverse dippers) have worse cardiovascular and kidney outcomes when compared to dippers.11,12,77 79 Whether the recently reported strategy of evening dosing to produce nocturnal dipping will improve outcomes in CKD patients, as has been described in individuals with essential hyperten- sion, remains to be established.80 82 The ERT was not asked to search for evidence of the effectiveness of established anti-hypertensive agents in lowering BP in patients with CKD, since it is generally believed that all such drugs are effective, although the sensitivity in individual patients may vary, as may be the side effects. Instead, the ERT focused on two issues. Firstly, studies that compared different BP targets were identified. In these studies, only the BP targets were randomized; the protocols varied with respect to the sequence of drugs and escalation of dose. Secondly the ERT searched for studies that included a comparison of different combinations of anti-hypertensive agents. In these studies, only the choice of first-line drug was randomized, with study protocols varying with respect to drug dose, use of concomitant agents and BP thresholds for drug titration (Table 5, see Methods for Guideline Development). The KDOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease (http:// www.kidney.org/professionals/KDOQI/guidelines_bp/index. contains details of clinical pharmacology and practical guidance on the use of the various agents to lower BP in CKD patients. 