Several studies in patients with chronic kidney disease or normal renal function have shown that high levels of tissue non-specific alkaline phosphatase (ALP) are associated with an increased risk of all cause and cardiovascular (CV) mortality. Considering the independent prognostic role of renal function, we investigated the possible association between ALP levels and estimated glomerular filtration rate (e-GFR) in a large cohort of hypertensive subjects. We enrolled 2157 never-treated uncomplicated hypertensive patients with ALP levels within normal range. In the whole population, e-GFR was strongly related to ALP (r = -0.43, P < 0.0001) with similar magnitude in females and in males, resulting ALP the second independent predictor of renal function. In a multiple linear regression model, both on crude (P < 0.001) and adjusted (P = 0.01) analyses age significantly modified the effect of a fixed increase in ALP (20 UI/L) on renal function so that the reduction in e-GFR associated to a 20 UI/L increase in ALP was of lower magnitude in younger patients and progressively of higher extent from 20 years of age onwards. In conclusion, present data indicate a significant relationship between ALP levels and e-GFR in uncomplicated hypertensive patients that is modulated by age and that persisted after adjusting for several confounders.