**May use loop diuretic for participants with advanced CKD. Unless side effects warrant change in therapy. Consider adding a fth antihypertensive medication. Or until clinical decision made that therapy should not be increased further. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; CKD, chronic kidney disease; DBP, diastolic blood pressure; SBP, systolic blood pressure; SPRINT, Systolic Blood Pressure Intervention Trial. www.kidney-international.org chapter 3 in proteinuria. Whether those changes translate to changes in hard outcomes is uncertain. In particular, we have no RCT evidence that, for example, targeting a proteinuria of <1 g compared to >2 g leads to fewer hard kidney or CVoutcomes. Due to the imprecision in the studies from a low number of events, beta-blockers (Supplementary Table S18182,183 ) and CCBs (Supplementary Table S19184 186 ) were found to have little or no difference compared to placebo or RASi for the CV and kidney outcomes (ESKD, doubling of serum creatinine, GFR decline) in patients with CKD with and without diabetes and severely increased levels of albuminuria. Only RASi has been extensively studied in appropriately powered trials. There was only 1 relevant direct renin inhibitor study, comparing aliskiren to the ARB losartan in patients without diabetes and varying levels of albuminuria, and there were no events in either arm (Supplementary Table S20187 ). Quality of evidence. The overall quality of the evidence comparing ACEi or ARB with placebo or standard of care in patients with CKD and severely increased albuminuria without diabetes is moderate. The quality of the evidence was down- graded because of study limitations, such as small numbers of events, inadequate reporting of sequence generation, and allo- cation concealment (Supplementary Table S15176 179,188,188a,189 and Supplementary Table S16190,191 ). 