Decreased Free 1,25-Dihydroxycholecalciferol Index in Patients with the Nephrotic Syndrome

Auwerx, Johan; Keyser, L. De; Bouillon, Roger; Moor, P. De

doi:10.1159/000183672

Cited by 36 publications

(21 citation statements)

References 17 publications

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“…In one study, free levels of 1,25(OH) 2 D, as determined by assessing the free index, were found low (12). However, with the same methodology, Chan et al (26) and Grymonprez et al (21) reported normal levels.…”

Section: Discussionmentioning

confidence: 94%

“…In contrast, other investigators report unchanged levels of DBP in patients with nephrotic syndrome (22). Likewise, total 1,25(OH) 2 D levels have been found to have decreased (12,21,23,24) or to have been unchanged (22,25) in patients with nephrotic syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…The data in the literature on changes in the DBP and total 1,25(OH) 2 D in nephrotic syndrome are equivocal. Some authors report lower concentrations of DBP (2,20,21), and in some studies a correlation between serum albumin and DBP levels was found (12,21). In contrast, other investigators report unchanged levels of DBP in patients with nephrotic syndrome (22).…”

Section: Discussionmentioning

confidence: 99%

“…However, in some studies the free 1,25(OH) 2 D concentration remained constant (6,8,9), while others found increased free levels (10). For nephrotic syndrome, some authors have reported no drop in free 1,25(OH) 2 D concentrations (11), whereas others found a reduced free index (12).…”

Section: Introductionmentioning

confidence: 99%

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Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding

Hoof¹,

Sévaux

Baelen

et al. 2001

European Journal of Endocrinology

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Objective: A novel assay was employed to study the free 1,25-dihydroxyvitamin D (1,25(OH) 2 D) concentrations in various populations with different levels of 1,25(OH) 2 D and vitamin D binding protein (DBP). Design: In 12 healthy women before and after 3 months of oral estrogen/progestagen treatment, 10 pregnant women, and 16 patients with a nephrotic syndrome and normal renal function, the concentrations of total and free 1,25(OH) 2 D, DBP and albumin were assessed. Methods: The total concentration of 1,25(OH) 2 D in serum was assessed using a radioreceptor assay. The free fraction of 1,25(OH) 2 D was measured using symmetric dialysis. DBP was assessed using single radial immunodiffusion. Serum albumin concentrations were measured on an automated analyzer. Results: In healthy women, the concentrations of total 1,25(OH) 2 D, free 1,25(OH) 2 D and DBP were 132^19 pmolalY 92^30 fmolal and 5X59^0X43 mmolalX After 3 months of estrogen/progestagen treatment, total 1,25(OH) 2 D and DBP levels rose significantly to 175^51 pmolal and 8X321 X59 mmolal P # 0X05 and P # 0X001; the free 1,25(OH) 2 D remained unchanged 1053 9 fmolal; not significant). Pregnant women had significantly higher levels of total 1,25(OH) 2 D and DBP 239^68 pmolal and 11X32^1X77 mmolal; both P # 0X001; the free 1,25(OH) 2 D level, however, was not different 104^27 fmolal; not significant). Unexpectedly, in patients with nephrotic syndrome, no lower DBP levels were found 5X36^0X84 mmolal relative to that in controls. Despite this, levels of both total 69^26 pmolalY P # 0X001 and free 1,25(OH) 2 D 532 8 fmolal; P # 0X001 were significantly lower than in controls. Albumin levels were lowered from 628^38 mmolal to 300^84 mmolal (P # 0.001). Conclusions: Higher estrogen levels result in higher DBP levels, with a parallel rise in total 1,25(OH) 2 D levels but without a change in the biologically active free fraction. The results in patients with nephrotic syndrome show that, with increasing glomerular protein leakage, the free 1,25(OH) 2 D concentration cannot be maintained.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding

Hoof¹,

Sévaux

Baelen

et al. 2001

European Journal of Endocrinology

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“…[41][42][43] We thus measured the levels of 25(OH)D 3 in urine of control rats and rats with CRF. As shown in Table 1, there was only a slight difference in urinary calcidiol concentrations between the two groups, ruling out the role of urinary loss in the observed calcidiol deficiency in CRF.…”

Section: Discussionmentioning

confidence: 99%

Reduced Hepatic Synthesis of Calcidiol in Uremia

Naud

Ouimet

et al. 2010

Journal of the American Society of Nephrology

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Calcidiol insufficiency is highly prevalent in chronic kidney disease (CKD), but the reasons for this are incompletely understood. CKD associates with a decrease in liver cytochrome P450 (CYP450) enzymes, and specific CYP450 isoforms mediate vitamin D 3 C-25-hydroxylation, which forms calcidiol. Abnormal levels of parathyroid hormone (PTH), which also modulates liver CYP450, could also contribute to the decrease in liver CYP450 associated with CKD. Here, we evaluated the effects of PTH and uremia on liver CYP450 isoforms involved in calcidiol synthesis in rats. Uremic rats had 52% lower concentrations of serum calcidiol than control rats (P Ͻ 0.002). Compared with controls, uremic rats produced 71% less calcidiol and 48% less calcitriol after the administration of vitamin D 3 or 1␣-hydroxyvitamin D 3 , respectively, suggesting impaired C-25-hydroxylation of vitamin D 3 . Furthermore, uremia associated with a reduction of liver CYP2C11, 2J3, 3A2, and 27A1. Parathyroidectomy prevented the uremia-associated decreases in calcidiol and liver CYP450 isoforms. In conclusion, these data suggest that uremia decreases calcidiol synthesis secondary to a PTH-mediated reduction in liver CYP450 isoforms. ] deficiency has also been demonstrated in patients with stages 3 and 4 chronic kidney disease (CKD) and in patients who are on dialysis. [1][2][3][4][5][6][7][8] In fact, low serum 25(OH)D 3 is so intimately associated with CRF that in one study, only 29 and 17% of patients with stages 3 and 4 CKD, respectively, had sufficient levels [defined as a serum 25(OH)D 3 concentrations Ͼ75 nmol/L or 30 ng/ml]. 2 A more recent study showed a prevalence of calcidiol insufficiency and deficiency as high as 98% in predialysis patients with a mean GFR of 18.3 ml/min. 4 Prevalence of low serum 25(OH)D 3 was 78 and 89% in two large cohorts of hemodialysis patients 9,10 and 87% in a large cohort of peritoneal dialysis patients. 11 The metabolic consequences of calcidiol defi-

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New perspectives on the vitamin D binding protein

Chun

2012

Cell Biochemistry & Function

222

150

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The serum vitamin D binding protein (DBP), also known as GC-globulin, is a multifunctional protein known for its role in the transport of vitamin D metabolites. DBP also binds fatty acids and actin monomers, preventing their polymerization that could be detrimental in the circulatory system. DBP may have immune functions independent of its role as a transporter of vitamin D. Because of the abundance of DBP, many aspects of its basic biochemistry were quickly established. Other features of vitamin D action, particularly transcriptional mechanisms of regulation, received greater focus and early interest in DBP centred on its value as a tool for population genetics because of its intriguing genetic variations. Nonetheless, knowledge of DBP mechanisms in physiology was obtained, and functions beyond vitamin D ligand binding were identified. With the recent increased attention regarding the benefits of vitamin D (bone health and immunological regulation), there has been a resurgence of interest in DBP. Because DBP is the primary transporter of vitamin D, it has a role in maintaining the total levels of vitamin D for the organism and in regulating the amounts of free (unbound) vitamin D available for specific tissues and cell types to utilize. This review will describe the findings on the basic biochemistry and molecular biology of DBP, the studies that elucidated its biological functions and highlight these results in light of the current renewed interest in vitamin D and human health, as well as the debate over what constitutes sufficient levels of vitamin D.

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Decreased Free 1,25-Dihydroxycholecalciferol Index in Patients with the Nephrotic Syndrome

Cited by 36 publications

References 17 publications

Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding

Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding

Reduced Hepatic Synthesis of Calcidiol in Uremia

New perspectives on the vitamin D binding protein

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