In adjusted analyses, ACE-Is were associated with a HR of 0.69 for kidney failure (95% CI 0.51 0.94) and 0.70 for the combined outcome of doubling of the baseline SCr concentration or kidney failure (95% CI 0.55 0.88). Patients with greater urinary protein excretion at baseline benefited more from ACE-I therapy (P 0.03 for kidney failure and P 0.001 for the combined outcome).141 The Work Group did not find heterogeneity with regard to the benefit of ACE-Is according to CKD stage; therefore, the guideline statements are not divided on this basis. Further- more, few RCTs with hard CVD or kidney-disease outcomes randomized patients to a diuretic or another agent in addition to an ACE-I or ARB; therefore, we have not included any guideline statements to support this practice. In fact, one RCT in individuals predominantly without CKD showed that the risk of doubling of the creatinine level was higher with an ACE-I hydrochlorothiazide combination than The clinical importance of this end point remains to be determined,193 as it may reflect a reversible hemodynamic effect. Finally, there is only limited quality evidence evaluating either differences in ACE-I versus ARB, or comparison of ACE-I plus ARB versus either ACE-I or ARB with regard to hard clinical outcomes (Supplemen- tary Tables 13 15 online). CVD. Only a few RCTs of BP agents have focused on CVD outcomes in subjects with CKD (Supplementary Tables 7 32 online); therefore, most of the data are from subgroup analyses of CKD patients from general population studies. 