A higher pulse pressure could theoretically be a consequence of RAS activation, but the lack of statistical evidence in the partial correlations (Table 2) for any association between renin and MAP or SBP in the separate subgroups (obesity and diabetes) does not favour a primary role for renin in the cascade, and rather suggests the opposite: pulse pressure induces early hemodynamic alterations in the glomerular microcirculation resulting in intrarenal RAS activation, prior to any other measurable sign of glomerular damage such as micro-albuminuria, proteinuria or decline in kidney function. This evidence concerns the gene REN and obesity disorder.