Biologic effect of 1,24(R)(OH)2D3 versus 1,25(OH)2D3 administration in chronic renal failure.
1,24(R)(OH)2D3 is a synthetic analogue of 1,25(OH)2D3 which binds to the same receptors as the physiologic metabolite with a lower affinity. The aim of the present study was to compare the activity of 1,24(R)(OH)2D3 and 1,25(OH)2D3 on several target organs in patients with chronic renal failure. Treatment with 1,24(R)(OH)2D3 at doses of either 1 or 2 micrograms daily was carried out in two groups of 9 patients, with serum creatinine of 4.61 +/- 1.59 and 4.66 +/- 1.46 mg/dl, respectively. Doses of 1,25(OH)2D3 were 0.5 and 1 microgram daily and were administered to 9 and 13 patients, serum creatinine of 4.52 +/- 1.67 and 4.3 +/- 1.16 mg/dl, respectively. Treatment periods were of 2 weeks. Administration of 1,25(OH)2D3, 1 microgram, induced significant increments of intestinal calcium absorption (ICA), ionized calcium, osteocalcin, serum creatinine, urine Ca/GFR, and a decrease in iPTH. 1,25(OH)2D3, 0.5 microgram, induced a significant increase in ICA and osteocalcin and a decrease in iPTH. Similarly 1,24(OH)2D3, 2 micrograms daily, significantly stimulated ICA and raised serum levels of osteocalcin and creatinine while lowering serum iPTH. In addition, 1,24(R)(OH)2D3 administration induced a significant fall of serum 1,25(OH)2D3. Following 1 microgram, only osteocalcin increased. Therefore, the dose of 2 micrograms of 1,24(R)(OH)2D3 has biologic activity similar to 0.5 microgram 1,25(OH)2D3 (4:1). However the activity ratio on osteocalcin production appears to be 2:1. In addition, 1,24(R)(OH)2D3 is able to inhibit renal tubular 1 alpha-hydroxylase. In conclusion 1,24(R)(OH)2D3 may prove to be useful in the treatment of metabolic bone disease.
Coen
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G
Chair of Nephrology, University of Rome La Sapienza, Italy.
Bondatti
F
F
Donato
G
G
Mazzaferro
S
S
Pasquali
M
M
Rosini
S
S
Sardella
D
D
Taggi
F
F
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D002117:Calcitriol / Q000627:therapeutic use; D002118:Calcium / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D004100:Dihydroxycholecalciferols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D007408:Intestinal Absorption; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D013250:Steroid Hydroxylases / Q000032:analysis; D013938:Thymidine Monophosphate / Q000652:urine
D004100:Dihydroxycholecalciferols; D015675:Osteocalcin; D013938:Thymidine Monophosphate; C023850:1 alpha,24-dihydroxyvitamin D3; D003404:Creatinine; D013250:Steroid Hydroxylases; D000469:Alkaline Phosphatase; D002117:Calcitriol; D006909:Hydroxyproline; D002118:Calcium