Calcitriol, calcidiol, parathyroid hormone, and fibroblast growth factor‐23 interactions in chronic kidney disease

Abstract

ObjectiveTo review the inter-relationships between calcium, phosphorus, parathyroid hormone (PTH), parent and activated vitamin D metabolites (vitamin D, 25(OH)-vitamin D, 1,25(OH)2-vitamin D, 24,25(OH)2-vitamin D), and fibroblast growth factor-23 (FGF-23) during chronic kidney disease (CKD) in dogs and cats.Data SourcesHuman and veterinary literature.Human Data SynthesisBeneficial effects of calcitriol treatment during CKD have traditionally been attributed to regulation of PTH but new perspectives emphasize direct renoprotective actions independent of PTH and calcium. It is now apparent that calcitriol exerts an important effect on renal tubular reclamation of filtered 25(OH)-vitamin D, which may be important in maintaining adequate circulating 25(OH)-vitamin D. This in turn may be vital for important pleiotropic actions in peripheral tissues through autocrine/paracrine mechanisms that impact the health of those local tissues.Veterinary Data SynthesisLimited information is available reporting the benefit of calcitriol treatment in dogs and cats with CKD.ConclusionsA survival benefit has been shown for dogs with CKD treated with calcitriol compared to placebo. The concentrations of circulating 25(OH)-vitamin D have recently been shown to be low in people and dogs with CKD and are related to survival in people with CKD. Combination therapy for people with CKD using both parental and activated vitamin D compounds is common in human nephrology and there is a developing emphasis using combination treatment with activated vitamin D and renin-angiotensin-aldosterone-system (RAAS) inhibitors.

Vitamin D metabolism in dogs and cats and its relation to diseases not associated with bone metabolism

“…The 24-hydroxylase activity is stimulated by calcitriol, which is an important protective mechanism against hypercalcemia (de Brito Galvao et al, 2013). In addition, the activity of this enzyme is also stimulated by FGF-23, so when serum phosphorus concentrations are high there is an increase in the synthesis and secretion of FGF-23, a hypophosphatemic peptide produced by bone tissue, mainly by osteocytes (de Brito Galvao et al, 2013).…”

“…In addition, the activity of this enzyme is also stimulated by FGF-23, so when serum phosphorus concentrations are high there is an increase in the synthesis and secretion of FGF-23, a hypophosphatemic peptide produced by bone tissue, mainly by osteocytes (de Brito Galvao et al, 2013). It is essential for the binding of FGF-23 with its receptor (de Brito Galvao et al, 2013). Klotho, a transmembrane protein, acts as a cofactor and is necessary for FGF-23 activity.…”

Calcium Disorders

“…3 With regard to calcium homeostasis, calcitriol primarily acts on the intestine, bone, kidney, and parathyroid gland. Dogs and cats, unlike humans, photosynthesize vitamin D inefficiently in their skin and therefore depend on vitamin D in their diet.…”

“…3 With regard to calcium homeostasis, calcitriol primarily acts on the intestine, bone, kidney, and parathyroid gland. • Hypocalcemia based on total serum calcium is often mild and less often requires calcium-specific treatment than does hypercalcemia.…”

Fibroblast Growth Factor 23

“…40,58,66,67,209 FGF23 increases as the stage of kidney disease increases in cats. 66 No matter the stage of kidney disease, and despite similar plasma creatinine concentrations, cats with hyperphosphatemia had higher plasma FGF23 concentrations than did normophosphatemic cats.…”