Vitamin D Metabolites and Calcium Metabolism in Patients with Nephrotic Syndrome and Normal Renal Function*

Goldstein, David; Haldimann, B; Sherman, David; Norman, Anthony W.; Massry, Shaul G.

doi:10.1210/jcem-52-1-116

Cited by 104 publications

(66 citation statements)

References 19 publications

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“…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%

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: 99%

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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“…Patients with liver disease (16-18) and the nephrotic syndrome (19,20) have DBP levels that are lower than normal. Low 1,25(OH)2D concentrations have been reported in these conditions by some investigators (21,22) but not by others (23,24). If levels are indeed lower, this circumstance may be caused by a reduction in the amount of 1,25(OH)2D bound to DBP, although abnormalities in hepatic or renal metabolism of vitamin D in such patients may be partially responsible.…”

Section: Introductionmentioning

confidence: 90%

Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease.

Bikle¹,

Gee²,

Halloran³

et al. 1984

J. Clin. Invest.

300

162

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Abstract. We measured the free concentration of 1,25-dihydroxyvitamin D (1,25[OHJ2D) using centrifugal ultrafiltration, and the level of vitamin D-binding protein (DBP) in 24 normal subjects, 17 pregnant subjects, and 25 alcoholic subjects with liver disease. Our objective was to determine whether the increase in total 1,25(OH)2D levels in pregnant women and the reduction in total 1,25(OH)2D levels in subjects with liver disease reflected a true difference in free 1,25(OH)2D levels or whether such differences were due solely to the variations in DBP levels (and thus, the amount of 1,25[OH]2D bound) in these groups. In subjects with liver disease the mean total 1,25(OH)2tD concentration (22.6±12.5 pg/ml) and the mean DBP concentration (188±105 fsg/ dl) were nearly half the normal values (41.5±11.5 pg/ ml and 404±124 ,g/dl, respectively, P < 0.001), whereas the mean free 1,25(OH)2D level was similar to normal values (209±91 fg/ml and 174±46 fg/ml, respectively). In contrast, in pregnant subjects the mean total 1,25(OH)2D level (82±21 pg/ml) and mean DBP level (576±128 Ag/dl) were significantly higher than normal (P < 0.001). Although the mean percent free 1,25-(OH)2D level in pregnant subjects was below normal (0.359±0.07% vs. 0.424±0.07%, P < 0.001), the mean free 1,25(OH)2D level was 69% higher than normal (294±98 fg/ml vs. 174±46 fg/ml, P < 0.001). When data from all three groups were combined, there was a linear correlation between total 1,25(OH)2D and DBP levels but not between DBP and percent free 1,25(OH)2D levels; the increased DBP levels in the pregnant subjects were associated with less of an effect on percent free 1,25(OH)2D than were the reduced DBP levels in the subjects with liver disease.Our data suggest that (a) free 1,25(OH)2D levels appear to be well maintained even in subjects with liver disease and reduced DBP levels, (b) free 1,25(OH)2D levels are increased during pregnancy despite the increase in DBP levels, and (c) free 1,25(OH)2D levels cannot be inferred accurately from measurements of total 1,25(OH)2D and DBP levels alone in subjects with various physiologic and pathophysiologic conditions.

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“…A lthough most patients with idiopathic nephrotic syndrome (NS) present with normal GFR, alterations of mineral homeostasis similar to those encountered with chronic renal failure are frequently identified, including hypocalcemia, reduced serum vitamin D metabolites, and elevated levels of immunoreactive parathyroid hormone (PTH) (1)(2)(3)(4)(5)(6). Metabolic balance studies have demonstrated intestinal malabsorption of calcium (5) as well as excessive urinary losses of various vitamin D metabolites and their binding proteins (2,7).…”

mentioning

confidence: 99%

“…Serum phosphorus concentration is usually normal (1,3,5), calcitriol remains normal in most patients (3,15), and despite low serum levels of ionized calcium, PTH levels are not consistently elevated (1,3,5,6,15). Thus, the mechanisms that result in altered BMD and bone histology in patients with NS before the reduction in GFR are still unclear.…”

mentioning

confidence: 99%

Increased Osteoblastic Activity and Expression of Receptor Activator of NF-κB Ligand in Nonuremic Nephrotic Syndrome

Freundlich¹,

Alonzo²,

Bellorín-Font³

et al. 2005

Journal of the American Society of Nephrology

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Patients with nephrotic syndrome (NS), even with normal GFR, often display altered mineral homeostasis and abnormal bone histology. However, the latter, mostly osteomalacia and increased bone resorption, cannot be readily explained by the prevalent concentrations of parathyroid hormone and vitamin D metabolites. The transmembrane receptor activator of NF-B ligand (RANKL) of osteoblasts is essential for osteoclast formation and differentiation. Osteoblasts activity and the expression of RANKL were tested in cultures of normal human osteoblasts with sera obtained from patients with NS and normal GFR (129 ؎ 26 ml/min per 1.73 m 2 ) during relapse and remission of their NS. Osteoblasts that were cultured in vitro with sera during relapse displayed elevated concentrations of alkaline phosphatase (AP) and increased expression of RANKL. By contrast, during remission, AP concentrations were significantly lower (P < 0.05) and RANKL expression notably attenuated or absent. AP correlated with the proteinuria (r ‫؍‬ 0.5, P < 0.05) and was not significantly affected by the therapeutic administration of corticosteroids. Whereas parathyroid hormone levels were normal (35 ؎ 21 pg/ml), the serum markers of bone formation (osteocalcin and bone-specific alkaline phosphatase) were lower during relapse compared with remission. Thus, sera from patients with NS and normal GFR stimulate the activity of osteoblasts and upregulate their expression of RANKL. These alterations, more prominent during clinically active NS, are transient and reversible upon remission. These disturbances of bone biology may play an important pathogenic role in the abnormal bone histology observed in patients with NS even before a decline in GFR occurs.

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Vitamin D Metabolites and Calcium Metabolism in Patients with Nephrotic Syndrome and Normal Renal Function*

Cited by 104 publications

References 19 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

Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease.

Increased Osteoblastic Activity and Expression of Receptor Activator of NF-κB Ligand in Nonuremic Nephrotic Syndrome

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