It would be helpful to clarify the role of diuretics as initial therapy in this population. 3.3 Role of dual therapy with RASi RASi have been shown to both lower BP and slow the pro- gression of certain types of kidney diseases independently of BP control. The strongest data come from studies of patients with CKD and diabetes with albuminuria, in which therapy with ACEi or ARB has shown improvement of kidney outcomes and potentially CV outcomes, as discussed above in Section 3.2. Some investigators have advocated the use of dual therapy with ACEi, ARB, and/or aliskiren to enhance the antiproteinuric and renoprotective effects. However, compared to monotherapy with ACEi or ARB, dual RASi therapy appears to cause more adverse effects, including hyperkalemia and AKI, that may outweigh any potential CV or kidney bene t. Recommendation 3.3.1: We recommend avoiding any combination of ACEi, ARB, and direct renin in- hibitor (DRI) therapy in patients with CKD, with or without diabetes (1B). This is a strong recommendation based on evidence from RCTs of suf cient duration to evaluate kidney and CV protection. There is growing evidence that dual RAS blockade with an ACEi, ARB, or DRI does not lead to long term CVorkidney bene t despite lowering proteinuria in the short term, but it leads to an increased risk of harm from hyperkalemia and AKI. This recommendation places a higher value on preventing harm from hyperkalemia and AKI than on lowering proteinuria. The combination of ACEi or ARB with MRA was bene cial in 1 large outcome trial; thus, our recom- mendations on combination therapy do not apply in this scenario. Key information Balance of bene ts and harms. In patients with CKD with and without diabetes, a large network meta-analysis compared dual blockade to monotherapy and included 17,750 participants. 