Blockade of RAAS in diabetic kidney disease Recent data from the VIVALDI trial (as described above) renal protection is being strongly questioned. However, until compared the renoprotective effects of telmisartan versus additional means of measuring kidney damage on a large valsartan and found that they had comparable renoprotec- scale are available, this endpoint may not have been meaning- tive effects.31 In other words, telmisartan was shown to be fully tested. Additional questions arise due to some confound- non-inferior at best to valsartan in slowing the progression ing factors in this study but the overwhelming evidence does of DKD. These ﬁndings were in contrast to the ﬁndings of uphold the superiority of telmisartan. Lastly, the secondary the AMADEO trial. There are several possible explanations endpoint of the study does suggest a renoprotective role for for the discrepant results including the methodology used aldosterone in DKD and we need well-designed randomized to measure the primary endpoint; urine protein to creati- trials for aldosterone antagonists like spironolactone. nine ratio in the AMADEO trial as compared to a 24-hour urine protein used in VIVALDI trial. Furthermore, in the VIVALDI trial, participants in the valsartan group required additional antihypertensives more frequently than the telmisartan group to achieve similar levels of blood pressure control. As described above, this important confounding factor was eliminated in the AMADEO trial where none of the treatment arms was favored with better blood pres- sure control.2 Lastly, the ethnicity of the participants in the VIVALDI trial was 80% Caucasian population compared to just 45% in the AMADEO trial, the implications of this ethnic homogeneity in VIVALDI with respect to ﬁnal analysis, are unclear. Role for aldosterone antagonism An important question that arises out of AMADEO trial is the use of aldosterone inhibiting agents to decrease protein- uria? Whole animal studies have suggested that aldosterone may contribute to oxidative stress, endothelial dysfunction and progressive kidney disease. Thereby, administra- tion of selective and non-selective MR antagonists may provide additional renal beneﬁts to the ACE inhibitors and ARBs.47 In a study published in 2004, Zhou et al showed that spironolactone may effectively reduce proteinuria in patients with CKD.47 Concerns remain with regard to the risk for hyperkalemia in patients with CKD, however. Prospec- tive randomized trials are necessary to conﬁrm the efﬁcacy and safety of antagonists of aldosterone on proteinuria and progression of CKD. Conclusions Data from the AMADEO trial demonstrate the superiority and/or non-inferiority of telmisartan as a renoprotective agent when compared to losartan, an already established ARB in the treatment of DKD. The superiority as outlined is based on the unique mechanism of action of this ARB and the pharmacokinetics which seem to be extremely favorable and ideal for treating DKD. 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