Systemic versus local regulation of vitamin D

PURPOSE OF REVIEW: New clinical data and technical advances challenge the long-held belief that the kidney is the predominant organ for vitamin D synthesis and degradation. This review highlights recent discoveries in systemic and local vitamin D regulation and their potential to influence future development of novel treatment concepts. RECENT FINDINGS: New clinical studies of calcifediol supplementation in anephric patients and in chronic kidney disease provide evidence for significant extra-renal vitamin D production. The clinical findings are supported by recent laboratory-based studies that utilize new technologies and mouse models. These studies identify the spleen and other organs as sites of vitamin D production, capable of compensating for a loss of kidney production in mice. The importance of local vitamin D metabolism is further underlined by the finding that secondary hyperparathyroidism in a model of chronic kidney disease could be attenuated by reducing vitamin D inactivation exclusively in the intestines. SUMMARY: Recent tissue-specific investigations of vitamin D metabolism identified several physiologically relevant and potentially targetable tissues beyond the kidney. These findings may provide the basis for novel treatments in kidney disease and other vitamin D-associated disorders with wider therapeutic windows than current approaches that act on the kidneys.