Vitamin D metabolites and calcium metabolism in patients with nephrotic syndrome and normal renal function.

Patients with nephrotic syndrome (NS) lose 25-hydroxyvitamin D3 (25OHD3) in the urine and have low blood levels of this metabolite. This abnormality may be responsible for the hypocalcemia, i.e. low ionized calcium. The mechanism of the hypocalcemia is not evident. It is possible that the low value of 25OHD results in low blood levels of other vitamin D metabolites, such as 1,25-dihydroxyvitamin D [1,25-(OH)2D] and 24,25-(OH)2D3; a deficiency of these compounds may cause defective intestinal absorption of calcium (alpha) and resistance to the calcemic action of parathyroid hormone (PTH), resulting in hypocalcemia. Studies were performed in 12 patients with NS and normal renal function to evaluate these questions. Blood levels of 25OHD, 1,25-(OH)2D, and 24,25-(OH)2D were all significantly (P < 0.01) lower in NS (4.0 +/- 0.8 ng/ml, 7.0 +/- 2.3 pg/ml, 1.8 +/- 0.2 ng/ml, respectively) compared to normal subjects (37.0 +/- 1.5 ng/ml, 37.0 +/- 1.2 pg/ml, and 3.4 +/- 0.2 ng/ml). Both alpha (0.21 +/- 0.2 vs. 0.27 +/- 0.1; P < 0.05) and the calcemic response to PTH (0.50 +/- 0.1 vs. 1.35 +/- 0.16 mg/dl; P < 0.01) in NS subjects were significantly lower than normal. The data indicate that 1) a deficient state of all of these vitamin D metabolites exists in patients with NS and normal renal function, 2) this abnormality underlies the defect in alpha and the resistance to the calcemic response to PTH, and all participate in the genesis of the hypocalcemia, 3) secondary hyperparathyroidism develops, and 4) both vitamin D deficiency and elevated blood levels of PTH are responsible for the bone lesions in these patients.