Dual blockade of the renin–angiotensin–aldosterone system in renal disease: what is the future?

To the Editor In their recently published paper, Lizakowski et al., 1 a renowned research group that focuses on the renin-angiotensin-aldosterone system (RAAS) in renal disease, demonstrated that the dual blockade of the RAAS with different combinations of drugs had a similar effect on several clinical and laboratory parameters in patients with nondiabetic proteinuric chronic kidney disease (CKD) to that observed for angiotensin II receptor blocker monotherapy.A combination of telmisartan with aliskiren led to a marked elevation of plasma renin levels (as compared with telmisartan with perindopril, telmisartan with eplerenone, or telmisartan in monotherapy), but the increase did not translate into worsening of renal function, aggravation of proteinuria, or urinary loss of transforming growth factor β (TGF -β), the key mediator and biomarker of renal fibrosis.We agree with the authors that these data may suggest lack of direct nephrotoxicity of renin.The authors pointed to the safety of telmisartan with aliskiren in patients with nondiabetic proteinuric renal disease and made it the key message of the paper, although they were cautious to limit their conclusions to early stages of CKD and patients with low cardiovascular morbidity.This study 1 adds new data to our current knowledge on therapeutic interventions on the RAAS.An extremely attractive, from the conceptual point of view, dual (or even triple) blockade of the RAAS in renal disease did not, however, translate into patient benefit in large -scale prospective clinical trials.The authors cited some of those "unsuccessful" studies in their paper (Aliskiren Trial in Type 2 Diabetes Using Cardio -Renal Endpoints [ALTITUDE] and Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial [ONTARGET]). 2,3 The renal community has often argued that, indeed, trials concerning dual RAAS blockade performed to date did not show benefits of this therapeutic approach, but in fact they were not designed to show renal benefit in carefully selected patients with well -defined renal disease.Hence, nephrologists were waiting for the results