Osteomalacia and Hyperparathyroid Bone Disease in Patients with Nephrotic Syndrome

Malluche, Hartmut H.; Goldstein, David; Massry, Shaul G.

doi:10.1172/jci109327

Cited by 91 publications

(48 citation statements)

References 12 publications

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“…These alterations in 1,25(OH) 2 D metabolism may be responsible for the reported alterations in bone metabolism in patients with nephrotic syndrome (30).…”

Section: Discussionmentioning

confidence: 92%

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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“…These alterations in 1,25(OH) 2 D metabolism may be responsible for the reported alterations in bone metabolism in patients with nephrotic syndrome (30).…”

Section: Discussionmentioning

confidence: 92%

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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“…Disturbances of mineral metabolism that potentially affect bone integrity have been recognized in patients with NS before the development of renal insufficiency and include hypocalcemia, reduced intestinal calcium absorption (5,6), low circulating levels of vitamin D metabolites (2,3,6,7), and occasional elevation of PTH (6,9). Furthermore, altered BMD (3,8) and abnormal bone histology (9,10) have also been documented in patients with NS and normal GFR.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, altered BMD (3,8) and abnormal bone histology (9,10) have also been documented in patients with NS and normal GFR. However, the abnormalities in BMD and bone histology do not correlate consistently with the prevailing concentrations of PTH or vitamin D metabolites (3,9,10). Similarly, reports on the degree and the type of bone histologic abnormalities still remain contentious (9,10,29,30).…”

Section: Discussionmentioning

confidence: 99%

“…However, in nonazotemic NS, contrary to patients with diminished GFR, serum phosphorus concentrations are rarely elevated (9,15,30), metabolic acidosis is not observed, and PTH is mostly normal (15,29,30). Whereas serum levels of 25OH vitamin D3 are frequently reduced during active NS as a result of urinary loses (2), those of calcitriol often remain normal even in patients with osteomalacia (3,10,29,30).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, important biologic consequences such as reduced bone mineral density (BMD) (3,8) and abnormal bone histology (9,10) have been documented. The latter include osteomalacia of varying degree (10) as well as excessive bone resorption resembling secondary hyperparathyroidism (9). Early identification and management of these abnormalities, even before the decline of GFR, could ameliorate the growth retardation and renal osteodystrophy that invariably affects children with more advanced chronic kidney disease (CKD) (11).…”

mentioning

confidence: 99%

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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 and Kidney Disease

Lemann¹,

Gray²,

Korkor³

1984

Nephrology

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Osteomalacia and Hyperparathyroid Bone Disease in Patients with Nephrotic Syndrome

Cited by 91 publications

References 12 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

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

Vitamin D and Kidney Disease

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