Skeletal Response to Treatment with 1,25-Dihydroxyvitamin D in Renal Failure

Abstract Background: Commercial intact parathyroid hormone (I-PTH) assays detect molecular form(s) of human PTH, non-(1-84) PTH, different from the 84-amino acid native molecule. These molecular form(s) accumulate in hemodialyzed patients. We investigated the importance of non-(1-84) PTH in the interpretation of the increased I-PTH in progressive renal failure. Methods: Five groups were studied: 26 healthy individuals, 12 hemodialyzed patients, and 31 patients with progressive renal failure subdivided according to their glomerular filtration rate (GFR) into 11 with a GFR between 60 and 100 mL · min−1 · 1.73 m−2, 12 with a GFR between 30 and 60 mL · min−1 · 1.73 m−2, and 8 with a GFR between 5 and 30 mL · min−1 · 1.73 m−2. We evaluated indicators of calcium and phosphorus metabolism and creatinine clearance (CrCl) in the progressive renal failure groups, and the HPLC profile of I-PTH and C-terminal PTH in all groups. Results: Only patients with a GFR <30 mL · min−1 · 1.73 m−2 and hemodialyzed patients had decreased Ca2+ and 1,25-dihydroxyvitamin D, and increased phosphate. In patients with progressive renal failure, I-PTH was related to Ca2+ (r = −0.66; P <0.0001), CrCl (r = −0.61; P <0.001), 1,25-dihydroxyvitamin D (r = −0.40; P <0.05), and 25-hydroxyvitamin D (r = −0.49; P <0.01) by simple linear regression. The importance of non-(1-84) PTH in the composition of I-PTH increased with each GFR decrease, being 21% in healthy individuals, 32% in progressive renal failure patients with a GFR <30 mL · min−1 · 1.73 m−2, and 50% in hemodialyzed patients, with PTH(1-84) making up the difference. Conclusions: As I-PTH increases progressively with GFR decrease, part of the increase is associated with the accumulation of non-(1-84) PTH, particularly when the GFR is <30 mL · min−1 · 1.73 m−2. Concentrations of I-PTH 1.6-fold higher than in healthy individuals are necessary in hemodialyzed patients to achieve PTH(1-84) concentrations similar to those in the absence of renal failure.

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The Use of 1,25-Dihydroxyvitamin D in Early Renal Failure

Annual Review of Medicine ◽

10.1146/annurev.me.43.020192.001303 ◽

1992 ◽

Vol 43 (1) ◽

pp. 227-237 ◽

Cited By ~ 43

Author(s):

W G Goodman ◽

J W Coburn

Keyword(s):

Renal Failure ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D

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1,25-Dihydroxyvitamin D downregulation of TGFα/EGFR expression and growth signaling: a mechanism for the antiproliferative actions of the sterol in parathyroid hyperplasia of renal failure

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2004.03.061 ◽

2004 ◽

Vol 89-90 ◽

pp. 507-511 ◽

Cited By ~ 27

Author(s):

Adriana Dusso ◽

Mario Cozzolino ◽

Yan Lu ◽

Tetsuhiko Sato ◽

Eduardo Slatopolsky

Keyword(s):

Renal Failure ◽

Parathyroid Hyperplasia ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Egfr Expression

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Lack of Relationship between Parathyroid Hormone and 1,25-Dihydroxyvitamin D in Chronic Renal Failure

Nephron ◽

10.1159/000186404 ◽

1991 ◽

Vol 58 (2) ◽

pp. 144-149 ◽

Cited By ~ 1

Author(s):

Martin Rudnicki ◽

Peter McNair ◽

Ib Transbøl ◽

Bent Nielsen

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D

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Effects of Retinoic Acid and 1,25-Dihydroxyvitamin D3 on IFN-gamma Secretion by Mononuclear Leukocytes from Nulliparous and Postparturient Dairy Cattle

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.70.3.92 ◽

2000 ◽

Vol 70 (3) ◽

pp. 92-101 ◽

Cited By ~ 14

Author(s):

Burim Ametaj ◽

Brian Nonnecke ◽

Ronald Horst ◽

Donald Beitz

Keyword(s):

Retinoic Acid ◽

Dairy Cattle ◽

Dairy Cows ◽

Dairy Cow ◽

Pokeweed Mitogen ◽

Mononuclear Leukocytes ◽

Combined Effects ◽

Ifn Gamma ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D

Individual and combined effects of several isomers of retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on interferon-gamma (IFN-gamma) secretion by blood mononuclear leukocytes (MNL) from nulliparous and postparturient Holstein cattle were evaluated in vitro. In the first experiment, effects on incubation period (24 to 72 hours) and time of supplementation (0 to 32 hours) with all-trans, 9-cis, 13-cis-, and 9,13-dicis-RAs (0 to 100 nM) on IFN-gamma secretion by pokeweed mitogen (PWM)-stimulated (0 and 10 mug/ml) MNL from nulliparous cattle were evaluated. In the second experiment, MNL from postparturient cows (bled at 0, 2, 4, and 16 days postpartum) were stimulated with PWM (0 and 10 mug/ml) in the presence of RA isomers (9-cis- or 9,13-dicis-RA; 0 to 100 nM), 1,25-(OH)2D3 (0 to 100 nM), or with combinations of these metabolites. The results show that individual isomers of RA had no effect on IFN-gamma secretion by PWM-stimulated MNL from nulliparous or postparturient cows. Furthermore 1,25-dihydroxyvitamin D3 inhibited IFN-gamma secretion by MNL from nulliparous and postparturient dairy cows; however, the degree of inhibition was greater when 9-cis- and 9,13-dicis-RA were also present in the cultures. Finally mononuclear leukocytes from postparturient dairy cows produced substantially less IFN-gamma than did MNL from nulliparous cattle. It is concluded that retinoic acids individually did not affect the capacity of leukocytes from dairy cattle to secrete IFN-gamma. This result is in marked contrast to studies in monogastric species indicating that RAs inhibit IFN-gamma secretion by peripheral blood T cells. Inhibition of IFN-gamma secretion by 1,25-(OH)2D3 was potentiated by 9-cis- and 9,13-di-cis-retinoics acids, suggesting that an excess of dietary vitamins A and D may compromise further the naturally immunosuppressed postparturient dairy cow. Additional research is necessary to determine if the combined effects of these metabolites on IFN-gamma secretion represent an increased susceptibility of the dairy cow to infectious diseases during the periparturient period. Lower secretion of IFN-gamma by MNL from postpartutient dairy cows, relative to nulliparous cattle, suggests that recently-calved cows are naturally immunosuppressed.

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