Possible mechanism of impaired calcium and vitamin D metabolism in nephrotic rats.
Patients who have nephrotic syndrome and normal renal function are hypocalcemic in spite of the elevated levels of serum parathyroid hormone (PTH) caused by a low serum concentration of 1,25-dihydroxyvitamin D[1,25(OH)2D], presumably because of its loss in urine. However, it has not been established whether the conversion of 25-hydroxyvitamin D[25(OH)D] into 1,25(OH)2D is impaired in the kidney. In this study, we examined the serum levels of vitamin D metabolites, and kinetics of renal 25(OH)D-1-hydroxylase activity in vitro, and nephrogenous cyclic AMP excretion in response to exogenous PTH administration in puromycin aminonucleoside-induced nephrosis in rats. Plasma ionized calcium and the serum levels of vitamin D metabolites were lower, and conversely, the serum PTH level was higher, in nephrotic rats than in controls. Serum 1,25(OH)2D levels were higher in 25(OH)D3-treated nephrotic rats than in untreated nephrotic rats, indicating that the low 1,25(OH)2D level in nephrotic rats is partially due to the low concentration of 25(OH)D. Although PTH levels were higher in nephrotic rats than in control rats, the Vmax of renal 25(OH)D-1-hydroxylase and nephrogenous adenosine 3',5'-monophosphate (cyclic AMP) excretion in response to exogenous PTH were significantly lower in nephrotic animals than in controls. These results suggest that abnormalities in calcium and vitamin D metabolism in nephrotic rats are partially attributable to impaired proximal tubular function.
Mizokuchi
M
M
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Kubota
M
M
Tomino
Y
Y
Koide
H
H
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000818:Animals; D002112:Calcifediol / Q000097:blood / Q000494:pharmacology; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000097:blood / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014807:Vitamin D / Q000378:metabolism*
D010281:Parathyroid Hormone; D014807:Vitamin D; D000242:Cyclic AMP; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium