Regulation of renal 25-hydroxyvitamin D-1-hydroxylase activity in the mouse after uninephrectomy.
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.
Almond
J R
JR
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Bales
C W
CW
Lobaugh
B
B
Klotman
P E
PE
Drezner
M K
MK
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000818:Animals; D002117:Calcitriol / Q000097:blood; D007668:Kidney / Q000201:enzymology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009392:Nephrectomy / Q000379:methods; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism
D014807:Vitamin D; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol