Vitamin D3 Repletion Improves Vascular Function, as Measured by Cardiorenal Biomarkers in a High-Risk African American Cohort

• Published in: Nutrients 2022-08, Vol.14 (16), p.3331
• Main Authors: Sinha, Satyesh K, Sun, Ling, Didero, Michelle, Martins, David, Norris, Keith C, Lee, Jae Eun, Meng, Yuan-Xiang, Sung, Jung Hye, Sayre, Michael, Carpio, Maria Beatriz, Nicholas, Susanne B
• Format: Article
• Language: English
• Subjects: African American; African Americans; Alfacalcidol; Biological markers; Biomarkers; Black or African American; Blood circulation disorders; Blood pressure; Blood Pressure Monitoring, Ambulatory; Calcifediol; Calcium (blood); cardiorenal biomarker; Cardiovascular diseases; Cardiovascular Diseases - complications; Cardiovascular Diseases - drug therapy; Cholecalciferol; Chronic illnesses; Chronic kidney failure; Complications and side effects; Creatinine; Demographic aspects; Diabetes; Diet therapy; Dietary supplements; Enzyme-linked immunosorbent assay; Epidermal growth factor receptors; FGF-23; Fibroblast growth factor 23; Fibroblast Growth Factors; Growth factors; Health aspects; Humans; Hypertension; Kidney diseases; Kidneys; Minority & ethnic groups; Nutrient deficiency; Osteopontin; PAI-1; Parathyroid Hormone; Physiological aspects; Placebos; Plasminogen Activator Inhibitor 1; Plasminogen activator inhibitors; Prevention; Pulse Wave Analysis; Renal Insufficiency, Chronic - complications; Risk analysis; Risk factors; Risk management; Vitamin D; Vitamin D deficiency; Vitamin D Deficiency - complications; Vitamin D Deficiency - drug therapy; Vitamin D3; Vitamins - therapeutic use; Wave propagation; Wave velocity
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu14163331

Background: 25-hydroxy vitamin D (Vit D)-deficiency is common among patients with chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD). African Americans (AAs) suffer disproportionately from CKD and CVD, and 80% of AAs are Vit D-deficient. The impact of Vit D repletion on cardio-renal biomarkers in AAs is unknown. We examined Vit D repletion on full-length osteopontin (flOPN), c-terminal fibroblast growth factor-23 (FGF-23), and plasminogen activator inhibitor-1 (PAI-1), which are implicated in vascular and kidney pathology. Methods: We performed a randomized, placebo-controlled study of high-risk AAs with Vit D deficiency, treated with 100,000 IU Vit D3 (cholecalciferol; n = 65) or placebo (n = 65) every 4 weeks for 12 weeks. We measured kidney function (CKD-EPI eGFR), protein-to-creatinine ratio, vascular function (pulse wave velocity; PWV), augmentation index, waist circumference, sitting, and 24-h-ambulatory blood pressure (BP), intact parathyroid hormone (iPTH) and serum calcium at baseline and study end, and compared Vit D levels with laboratory variables. We quantified plasma FGF-23, PAI-1, and flOPN by enzyme-linked immunosorbent assay. Multiple regression analyzed the relationship between log flOPN, FGF-23, and PAI-1 with vascular and renal risk factors. Results: Compared to placebo, Vit D3 repletion increased Vit D3 2-fold (p < 0.0001), decreased iPTH by 12% (p < 0.01) and was significantly correlated with PWV (p < 0.009). Log flOPN decreased (p = 0.03), log FGF-23 increased (p = 0.04), but log PAI-1 did not change. Multiple regression indicated association between log flOPN and PWV (p = 0.04) and diastolic BP (p = 0.02), while log FGF-23 was associated with diastolic BP (p = 0.05), and a trend with eGFR (p = 0.06). Conclusion: Vit D3 repletion may reduce flOPN and improve vascular function in high risk AAs with Vit D deficiency.