Systemic versus local regulation of vitamin D

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.

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.

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.