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 ). For studies of ACEi versus placebo or standard of care, some outcomes (ESKD, doubling of serum creatinine, and CV events) exhibited moderate quality of the evidence, downgraded because of study limitations (Supplementary ). The quality of evidence for other antihypertensive thera- pies in the population of CKD patients without diabetes and severely increased albuminuria was lower than the evidence for RASi, as it has only been examined in a limited number of RCTs for MRA of rather short duration and powered for surrogate outcomes (Supplementary Table S17192 195 ). Values and preferences. The presence of severely increased albuminuria and CKD is associated with a higher prevalence of CV disease, progressive CKD, and attendant loss of quality In the opinion of the Work Group, most well- informed patients with CKD and severely increased albu- minuria would place emphasis on preventing CV outcomes in addition to preventing CKD progression. Resource use and costs. The risks, bene ts, resource use, and costs of RASi therapy should be considered when treating patients with CKD. The costs of generic RASi medication are generally low. However, the use of RASi in patients with CKD G1 G4 with A3, especially those with G4, necessitates patient education (e.g., when to pause RASi), repeat lab testing, vigilance to prevent hyperkalemia and AKI due to volume depletion and other events, as well as repeat visits to restart RASi if it has been stopped during a hospitalization. 