Endocrine Abstracts

End stage renal disease (ESRD) is characterised by decreased renal synthesis of 1,25-dihydroxyvitamin D (1,25D). Therapeutic use of 1,25D analogues for the management of renal bone disease is routine. However ESRD patients are also deficient in 25D (the immediate precursor of 1,25D). Since 2014 UK guidelines recommend diagnosis and treatment of 25D deficiency/insufficiency in people with chronic kidney disease, but make no recommendations for dosage or monitoring. This, togeth...

It is now recognized that vitamin D influences the innate immune system and recent studies have highlighted the importance of local synthesis of 1,25-dihydroxyvitamin D (1,25D) for these responses. Production of 1,25D from 25-hydroxvitamin D (25D) is catalyzed by 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1; 1α-OHase). Vitamin D is metabolized by 24-hydroxylase (CYP24A1; 24-OHase). A key part of the innate immune response is pathogen recognition by the toll-like recep...

We have recently demonstrated expression of a functional calcium sensing receptor (CaSR) in human aortic smooth muscle cells (HAoSMC) and human arteries and demonstrated a correlation between CaSR expression and medial calcification (a major cause of cardiovascular mortality in chronic kidney disease). Apoptosis of vascular SMC occurs early in the development of calcification and apoptotic bodies accumulate calcium. Here, we have examined CaSR-mediated signalling pathways in H...

Reduced renal synthesis of 1,25-dihydroxyvitamin D (1,25(OH)2D) from 25-hydroxyvitamin D (25OHD) in end stage renal disease (ESRD) results in low serum 1,25(OH)2D. This appears to be due to reduced renal cell function and elevated serum fibroblast growth factor 23 (FGF23). Treatment strategies have therefore focussed on 1,25(OH)2D or its synthetic analogues, alfacalcidol or paricalcitol. However this overlooks 25-hydroxyv...

Reduced renal synthesis of 1,25-dihydroxyvitamin D (1,25(OH)2D) from 25-hydroxyvitamin D (25OHD) in end stage renal disease (ESRD) results in low serum 1,25(OH)2D. This appears to be due to reduced renal cell function and elevated serum fibroblast growth factor 23 (FGF23). Treatment strategies have therefore focussed on 1,25(OH)2D or its synthetic analogues, alfacalcidol or paricalcitol. However this overlooks 25-hydroxyv...

Vitamin D deficiency is associated with the development of some cancers and in vitro 1,25-dihydroxyvitamin D (1,25D) reduces cell proliferation. We suggest that modification of tissue specific immune responses, as a consequence of local synthesis of 1,25D, may be key. To assess the impact of serum 25D on the risk of bladder cancer we conducted a systematic review. To test our hypothesis, expression of vitamin D signalling components and the synthesis of 1,25D were exa...

Accelerated medial calcification is a major cause of premature cardiovascular mortality in people with chronic kidney disease. Evidence suggests that the concentration of extracellular Ca2+ and vascular smooth muscle cells play a pivotal role in the pathogenesis of vascular calcification. Extracellular Ca2+ is detected by the calcium-sensing receptor (CaSR). The CaSR is a G protein-coupled receptor that is expressed in a range of tissues, but characteriza...