Table 1.
Effects of calcitriol
| ↓ 1-α-hydroxylase activity and ↑ 24-hydroxylase– normal negative feedback loop27 |
| ↑ Ionized calcium (calcemic effects)5,6 |
| ↑ GI absorption calcium and phosphorus (genomic)28 |
| ↑ Ca pump ATPase6 |
| ↑ Calbindins6 |
| ↑ Formation of calcium channels in microvillar membranes6 |
| ↑ Renal resorption Calcium and Phosphorus – when blood concentration a bit low29,30 |
| ↑ Osteoclastic Bone Resorption31,32 |
| ↓ Renal Resorption Calcium – when blood calcium is too high |
| CaR effect – CaR in Henle's loop calcitriol induced33,34 |
| ↓ PTH Secretion – 2° ↑ Ionized Calcium)35 |
| ↓ PTH Synthesis – genomic inhibition36 |
| Upregulation of VDR & CaR – parathyroid glands and elsewhere23,37 |
| Parathyroid Gland Set Point Control38 |
| ↑ Synthesis of CaR, G proteins, calcium channels |
| Prevention and reversal of PTG hyperplasia -anti-proliferative effects – Counteracts effects on TGF-α and EGFR interactions induced by phosphorus39–41 |
| ↓ Renal EGFR activation —↓TACE10 |
| ↓ TACE (direct effect)42 |
| ↓ RAAS Activity43 |
| ↓ renin synthesis (renin gene contains VDRE)44 |
| ↑ FGF-23 → ↓ PTH secretion (except in advanced CKD)45–47 |
| ↑ phosphaturia & ↓ intestinal absorption (secondary to lowered calcitriol)48 |
| ↓ Vascular mineralization in CKD – induction of ↑ FGF-23 → phosphaturia49–54 |
| Reversal of renal osteodystrophy from ↑ PTH55,56 |
| Direct Renoprotective Effects – independent of ↓ PTH10,57–59 |
| ↓ Podocyte injury60 |
| ↓ Loss, hypertrophy, apoptosis61 |
| Maintain slit pore membrane dynamics |
| ↑ Nephrin62–66 |
| ↑ Podocin62–66 |
| ↓ Desmin (injury molecule)62–66 |
| Mesangial cells – integrity preserved, ↓ proliferation |
| Anti-Fibrotic67 |
| ↓ Myofibroblast activity68–70 |
| ↓ Extracellular matrix from myofibroblasts68–70 |
| ↓ TGF-β68 |
| ↓ SERPINE-168–70 |
| ↑ MMP-8 (cleaves collagen)68–70 |
| ↑ BMP7 (antagonist of TGF-β)68–70 |
| ↓EMT68–70 |
| Antiproliferative effects (independent of PTH)-↓Glomerulosclerosis71 |
| ↓ RAAS Activity72–74 |
| ↓ Renin synthesis (renin gene contains VDRE)75 |
| ↓ ANG II generation → ↓ fibrogenic activity75 |
| ↓ EMT, ↓TGF-β, ↓ CTGF-β76 |
| ↑ Megalin expression – ↑ 25(OH)-vitamin D/VDBP uptake into proximal tubules77 |
| ↓ albuminuria78 |
| ↑ circulating 25(OH)-vitamin D78 |
| ↑ generation of calcitriol by providing more substrate78 |
| Anti-Inflammatory72,79 |
| ↓ NF-κβ (transcription factor) & ↓TGF-β 1 |
| ↑ Uptake of 25(OH)-vitamin D at peripheral tissues –induction of members of the LDL family of receptors thought to be involved80 |
| ↑ Klotho – counteracts damaging effects of Ang II49,50,54,81,82 |
| ↓ Blood pressure83,84 |
| 95 kidney genes are controlled by calcitriol some of which provide local tissue immunologic and antiproliferative effects and many indicated above have renoprotective effects as well as cardioprotective effects.85 |