Oral 1,25‐dihydroxyvitamin D 3 loading test in normal subjects and patients with chronic renal failure under haemodialysis

Summary: The present study was designed to determine the criterion for 1,25‐dihydroxyvitamin D 3 (1,25 (OH) 2 D 3 ) loading test in normal subjects and haemodialysis patients. Fourteen normal subjects were administered 1.0 μg of 1,25(OH) 2 D 3 per os and serum 1,25(OH) 2 D was monitored every hour up to 6 h afterwards under conditions of overnight fasting, and six haemodialysis patients were administered 2.0 μg of 1,25(OH) 2 D 3 per os and serum 1,25(OH) 2 D was monitored every 2 h up to 12 h afterwards. Peak time of serum 1,25 (OH) 2 D varied between 2 and 5 h after administration in normal subjects. However, there was a good correlation between the maximum increment of 1,25(OH) 2 D (maxΔ1,25(OH) 2 D) and the increment at 4 h after administration (Δ1,25(OH) 2 D(4 h)). the peak time of Δ1,25(OH) 2 D in six haemodialysis patients was also at 4 h after administration. From these observations, Δ1,25(OH) 2 D(4 h) was evaluated in subsequent studies. Twenty‐six normal subjects and 24 haemodialysis patients were administered 0.5–2.0 μg of 1,25(OH) 2 D 3 per os, according to their bodyweights, under conditions of overnight fasting. Blood samples were drawn for measuring 1,25(OH) 2 D prior to and 4 h after administration. Δ1,25(OH) 2 D(4 h) showed good correlation with the dose of 1, 25 (OH)2D3 adjusted by bodyweight (ng/kg bodyweight). the ratio of Δ1,25(OH) 2 D(4 h) and adjusted dose of 1,25(OH) 2 D 3 was more than 2.0 in all normal subjects (range: 1.97−2.89, mean ± SD: 2.38 ± 0.287). Moreover, the ratio of Δ1,25(OH) 2 D(4 h) and adjusted dose of 1,25(OH) 2 D 3 showed a good reproducibility (CV%= 5.7 Δ 0.32, n =5), and did not depend on the administered dose of 1,25(OH) 2 D 3 , suggesting that this ratio is a good parameter for the intestinal absorption of 1,25(OH) 2 D 3 . In haemodialysis patients, the mean ratio of Δ1,25 (OH) 2 D(4 h) and adjusted dose of 1,25(OH) 2 D 3 was 2.14 Δ 0.489, which was not significantly different from the ratio in normal subjects, suggesting that, fundamentally, there was no impairment of intestinal absorption of 1,25(OH) 2 D 3 in these patients. However, low ratios of Δ(4 h) and the dose of 1,25(OH) 2 D 3 with low basal levels of 1,25(OH) 2 D were observed in some patients (less than 1.5 in four patients), suggesting that there exist haemodialysis patients with malabsorption of 1,25(OH) 2 D 3 . From these results, the criterion for normal response in 1,25(OH) 2 D loading test was proposed, namely, that the ratio of Δ1,25(OH) 2 D(4 h) and adjusted dose of 1,25(OH) 2 D 3 be more than 2.0.