Doxercalciferol (TSA 840) is a synthetic vitamin D2 analog, suppressing parathyroid synthesis and secretion, used to treat secondary hyperparathyroidism and metabolic bone disease.

Doxercalciferol (100 or 300 pg/g b.w.) normalizes serum calcium and parathyroid hormone (PTH) levels in nephrectomy treated mice. Doxercalciferol (300 pg/g b.w.) significantly reduces osteitis fibrosa in nephrectomy treated mice. [1] Doxercalciferol results in significant decrease in cardiac hypertrophy and improves cardiac function in rats fed a high salt (HS) diet. Doxercalciferol treatment leads to a significant decrease in plasma brain natriuretic peptide (BNP) level and tissue atrial natriuretic factor (ANF) mRNA level in rats fed a high salt (HS) diet. Doxercalciferol also significantly reduces the level of protein kinase C-α (PKCα) suggesting that PKC-mediated cardiac hypertrophy may be associated with vitamin D deficiency. [2] Doxercalciferol decreases proteinuria, podocyte injury, mesangial expansion, and extracellular matrix protein accumulation in Diet-induced obesity (DIO) mice. Doxercalciferol also decreases macrophage infiltration, oxidative stress, proinflammatory cytokines, and profibrotic growth factors in DIO mice. Doxercalciferol also prevents the activation of the renin-angiotensin-aldosterone system including the angiotensin II type 1 receptor and the mineralocorticoid receptor in DIO mice. [3] Doxercalciferol combined with Losartan most effectively prevents albuminuria, restored glomerular filtration barrier structure, and dramatically reduces glomerulosclerosis in a dose-dependent manner in mice. Doxercalciferol combined with Losartan virtually prevents morphological and molecular changes in diabetic kidneys of mice. [4]