Abstract
The relation of alkaline phosphatase (ALP) with chronic kidney disease (CKD) is still uncertain. We aimed to examine the prospective association between serum ALP and CKD progression, and the modifying effect of serum ALP on folic acid in preventing CKD progression in treated hypertensive patients. This is a post-hoc analysis of 12,734 hypertensive adults with relevant measurements and without liver disease at baseline from the renal sub-study of the China Stroke Primary Prevention Trial, where participants were randomly assigned to daily treatments of 10 mg enalapril and 0.8 mg folic acid, or 10 mg enalapril alone. The primary outcome was CKD progression, defined as a decrease in estimated glomerular filtration rate (eGFR) of ≥30% and to a level of <60 ml/min/1.73 m2 if baseline eGFR was ≥60 ml/min/1.73 m2; or a decrease in eGFR of ≥50% if baseline eGFR was <60 ml/min/1.73 m2; or end-stage renal disease. Over a median of 4.4 years, in the enalapril only group, participants with baseline serum ALP≥110IU/L (quartile 4) had a significantly higher risk of CKD progression (3.4% vs 2.3%; adjusted OR,1.61; 95%CI:1.11, 2.32), compared with those with ALP<110IU/L. For those with enalapril and folic acid treatment, compared with the enalapril only treatment, the risk of CKD progression was reduced from 3.4 to 2.1% (adjusted OR, 0.53; 95%CI:0.34, 0.83) among participants with baseline ALP≥110IU/L, whereas there was no significant effect among those with ALP<110IU/L. In hypertensive patients, higher serum ALP was associated with increased risk of CKD progression, and this risk was reduced by 47% with folic acid treatment.
Highlights
Chronic kidney disease (CKD) is a global public health problem, affecting more than 500 million people worldwide (Chen et al, 2019)
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We found that among hypertensive adults, those participants with higher serum ALP had significantly increased risk of CKD progression
Summary
Chronic kidney disease (CKD) is a global public health problem, affecting more than 500 million people worldwide (Chen et al, 2019). It is important to identify more risk factors of CKD that would reduce the public health burden and serious clinical consequences by leading to early detection and prevention. Previous studies have found an obvious association between liver and renal disease, and suggested that liver damage and CKD may share some common mechanisms, such as oxidative stress and inflammation (Contreras et al, 2007; Er et al, 2020; Sansoè et al, 2020). It has been reported that ALP is an important risk factor for cardiovascular diseases (CVD) and mortality (Park et al, 2013; Kunutsor et al, 2014; Kabootari et al, 2018), owing to its role in endothelial dysfunction, inflammation, and oxidative stress (Haarhaus et al, 2017). Few prospective studies have examined the possible relation of ALP and the development of CKD in the general population
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