Regulation of renal 25-hydroxyvitamin D-1-hydroxylase activity in the mouse after uninephrectomy

• Published in: Endocrinology (Philadelphia) Vol. 124; no. 5; p. 2118
• Main Authors: Almond, J R, Bales, C W, Lobaugh, B, Klotman, P E, Drezner, M K
• Format: Journal Article
• Language: English
• Published: United States 01.05.1989
• Subjects: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - metabolism; Animals; Calcitriol - blood; Kidney - enzymology; Kidney - physiology; Mice; Mice, Inbred C57BL; Nephrectomy - methods; Steroid Hydroxylases - metabolism; Vitamin D - metabolism
• ISSN: 0013-7227
• DOI: 10.1210/endo-124-5-2118

Although renal hypertrophy occurs rapidly after uninephrectomy, restoring the majority of renal excretory function, it remains unknown whether similar compensatory mechanisms maintain 1,25-dihydroxyvitamin D production (and calcium homeostasis). To address this issue we compared plasma calcitriol levels and renal 25-hydroxyvitamin D (25OHD)-1-alpha-hydroxylase activity (in remnant kidneys) of mice at various times after uninephrectomy to similar observations obtained in sham-operated age- and sex-matched controls. At all times postoperatively, the uninephrectomized mice sustained plasma 1,25-dihydroxyvitamin D levels no different from those of shams. Maintenance of calcitriol production occurred secondary to a significant increment of renal 25OHD-1 alpha-hydroxylase activity (per mg DNA) 1-3 days after surgery when renal mass/function remained markedly depressed. In contrast, 10 and 21 days postoperatively, when hypertrophy was complete, enhanced enzyme function was no longer apparent. Throughout this period a significant inverse linear correlation existed between renal 25OHD-1 alpha-hydroxylase and the renal mass as well as glomerular filtration rate and renal blood flow. The variance in enzyme activity resulted in maintenance of a stable renal 25OHD-1 alpha-hydroxylase (per animal or total kidney mass) at all times investigated postuninephrectomy. Such compensatory regulation of vitamin D metabolism after unilateral kidney extirpation may be an important factor contributing to the low morbidity/mortality in the renal donor.