Endocrine Abstracts

The crucial role of vitamin D in mineral homeostasis is well known. However recent evidence has documented its importance for immunomodulation and inflammation. The kidney is the main source for the endocrine synthesis of the active metabolite 1,25-dihdroxyvitamin D3 (1,25D3), with expression of the key enzyme, 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha-OHase). Our aim was to investigate the alteration of the vitamin D hormonal system in renal failure and assess the impact of an inflammatory environment. 1a-OHase, vitamin D receptor (VDR) and 24-hydroxylase (24-OHase) and inflammatory markers such as macrophage chemoatractant protein 1 (MCP1) and toll-like receptor 4 (TLR-4) were analysed in a large number of patients (n=102) undergoing kidney biopsy for underlying renal disease. TaqMan real-time PCR was used for the quantification of kidney mRNA with 18S as housekeeping gene. Serum and 24h-urine samples were used to document underlying renal function, endocrine parameters and inflammatory markers. Serum 1,25D3 levels declined with deteriorating renal function (p<0.001). This was in part due to declining serum 25D3 levels, the substrate for 1alpha-OHase. Serum 25D3 (p<0.001), but not 1,25D3 levels were correlated with weight of the patients. No compensatory increase of 1alpha-OHase or suppression of 24-OHase mRNA expression was observed. However, VDR mRNA expression appeared to increase with deteriorating renal function (p=0.054). In contrast 1alpha-OHase, 24-OHase, VDR mRNA expression was highly correlated with markers reflecting local inflammation, such as MCP1 (p=0.004) or TLR4 (p=0.002) mRNA. 24-OHase mRNA expression correlated with urinary MCP1 (p=0.019). Increased renal MCP1 mRNA and urinary MCP1 were associated with higher serum 25D3 (p=0.49) and 1,25D3 (p=0.032) levels. We conclude, that despite impaired renal function, no compensatory up-regulation of the renal vitamin D hormonal system can be observed. However, increased serum vitamin D levels with renal inflammation underlines the importance of vitamin D for an inflammatory environment.