Vitamin D metabolism in nephrotic rats.
It is well known that patients with nephrotic syndrome and normal renal function have hypocalcemia in spite of high PTH concentration, caused by the low serum concentration of the active vitamin D metabolite, 1,25(OH)2D, presumably due to its loss in urine. However, it has been uncertain whether the conversion of 25(OH)D into 1,25(OH)2D in the kidney is impaired. In this study, we examined the responsibility of 1,25(OH)2D in PAN-induced nephrotic rats. Sprague-Dawley rats weighing 250 g were given subcutaneous injections 1.5 mg/100 g PAN for 12 days prior to use. Some of these rats were given intraperitoneal injection of 100 IU of 25(OH)D3 for 3 days prior to use and of 10 IU of PTH. We measured Ca2+ in plasma, vitamin D metabolites and mid-molecule PTH in serum, renal 25(OH)D-1-hydroxylase activity in vitro, and response of nephrogenous cyclic AMP to exogenous PTH administration. In nephrotic rats, plasma Ca2+, serum 25(OH)D and 1,25(OH)2D were lower than in control rats, and the serum PTH level was higher than in controls. In 25(OH)D3-injected nephrotic rats, Ca2+ and 1,25(OH)2D were higher than in nephrotic rats, indicating that the decreased level of 1,25(OH)2D in nephrotic rats was partially due to the low serum level of 25(OH)D. Despite the elevation of the serum level of PTH, the Vmax of renal 25(OH)D-1-hydroxylase in nephrotic rats was lower than in controls. Response of nephrogenous cyclic AMP to PTH in nephrotic rats was lower than in controls. Although nephrotic rats had higher PTH levels than control rats, Vmax of renal 25(OH)D-1-hydroxylase and response of cyclic AMP to exogenous PTH administration in nephrotic rats were lower than in controls, suggesting that abnormalities of calcium metabolism in patients with nephrotic syndrome might be partially attributed to the impaired renal response to PTH.
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 / Q000032:analysis; D000818:Animals; D002112:Calcifediol / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis; D008297:Male; D009404:Nephrotic Syndrome / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D014807:Vitamin D / Q000378:metabolism*
D010281:Parathyroid Hormone; D014807:Vitamin D; D000242:Cyclic AMP; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002112:Calcifediol