Abstract
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.
Highlights
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
There were no significant differences between males and females for ALP as well as for systolic BP (SBP), diastolic BP (DBP), LDL-cholesterol and smoking
Serum levels of phosphorus, calcium, and uric acid (UA) were significantly higher in males, so as estimated glomerular filtration rate (e-GFR), that resulted normal in both groups
Summary
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. Numerous studies in patients with chronic kidney disease (CKD) have shown that high levels of ALP are associated with an increased risk of CV and all-cause mortality[2,3,4]. A strong association between serum ALP levels and reduced endothelium-dependent vasodilation, an independent predictor of CV events, was demonstrated in a large cohort of hypertensive patients[12]. It is well known the strong link between renal function and CV outcome across all CKD stages. Experimental evidence suggests that ALP may directly affect renal function by increasing adenosine production and enhancing reno-vascular responses
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