METHODS: We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to <10 ml per minute per 1.73 m2, a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from cardiovascular causes.
RESULTS: A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P<0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P = 0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups.
CONCLUSIONS: Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EudraCT number, 2017-002971-24.).
MAIN METHODS: Cell mineralization capacity of phytoestrogens was investigated by evaluating calcium, phosphate content and alkaline phosphatase activity. Bone related markers, osteocalcin and osteonectin, responsible in maintaining mineralization were also measured.
KEY FINDINGS: BPA is significantly interfering with bone mineralization in hFOB 1.19 cells. However, the enhanced mineralization efficacy of daidzein and genistein (particularly at a dose of 5 and 40 μg/mL, respectively) was evidenced by increasing calcium and phosphate content, higher ALP activity, compared to the untreated BPA group. The quantitative analyses were confirmed through morphological findings. Osteocalcin and osteonectin levels were increased in phytoestrogens-treated cells. These findings revealed the potential effect of phytoestrogens in reverting the demineralization process due to BPA exposure in hFOB 1.19 cells.
SIGNIFICANCE: We found that osteoblast differentiation and mineralization were maintained following treatment with phytoestrogens under BPA exposure.