Arterial stiffness is typical feature of vascular remodeling in chronic kidney disease (CKD). Increased arterial stiffness raises flow and pressure pulsatility and is considered the principle pathogenic mechanism of isolated systolic hypertension, left ventricular hypertrophy, and congestive heart failure. Apart from the impact of arterial stiffness on left ventricular afterload, downstream transmission of pressure pulsatility to the level of microcirculation is suggested to promote injury of other susceptible organs. This may be of particular importance for kidney injury progression, since passive renal perfusion along with low resistance and input impedance in renal microvessels make kidneys particularly vulnerable to the damaging effect of systemic pulsatile pressure. Recent studies have provided evidence that arterial stiffness culminates in elevated pulsatility and resistance in renal microvasculature, promoting structural damage of small intra-renal arterioles. Further, prospective observational studies have shown that reduced aortic compliance is closely associated with the annual rate of renal function decline and represents independent predictor of kidney injury progression to end-stage renal disease among patients with CKD. This article provides insights into the cross-talk between macrocirculation and renal microcirculation and summarizes the currently available clinical evidence linking increased arterial stiffness with kidney disease progression.