Bone histology in patients with nephrotic syndrome and normal renal function

Mittal, Sanjeev; Dash, Suresh C.; Tiwari, S. C.; Agarwal, Sanjay Kumar; Saxena, Sanjeev; Fishbane, Steven

doi:10.1046/j.1523-1755.1999.00413.x

Cited by 46 publications

(48 citation statements)

References 18 publications

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“…The significantly reduced BSAP levels in our patients who had NS during remission but still were on glucocorticoid therapy compared with those who were off steroids may reflect reduced osteoblastogenesis and could result in diminished bone mineral mass (8,44,45). Studies have demonstrated defective bone mineralization and an inverse correlation between the administered dose of corticosteroid therapy and bone formation rates in bone biopsies of adults (29) and more recently in children with NS (37). However, children may display preserved bone mineral mass even shortly after the cessation of intermittent highdose glucocorticoid therapy for clinically active NS, suggesting the capability of the young skeleton to rapidly regain previous steroid-induced bone losses (46).…”

Section: Discussionmentioning

confidence: 88%

“…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). Furthermore, despite histologic evidence of secondary hyperparathyroidism in some patients, serum concentrations of PTH are frequently normal (10,29).…”

Section: Discussionmentioning

confidence: 98%

“…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%

“…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). Furthermore, despite histologic evidence of secondary hyperparathyroidism in some patients, serum concentrations of PTH are frequently normal (10,29). In contrast, some patients with elevated PTH and/or reduced vitamin D metabolites may display normal or near-normal bone histology (10,29,30).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, despite histologic evidence of secondary hyperparathyroidism in some patients, serum concentrations of PTH are frequently normal (10,29). In contrast, some patients with elevated PTH and/or reduced vitamin D metabolites may display normal or near-normal bone histology (10,29,30). Therefore, the role of other factors that affect bone cellular activity and thereby bone histology need to be considered.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

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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Quantitation of 25-OH-Vitamin-D2 and 25-OH-Vitamin-D3 in Urine Using LC-MS/MS

Carlow¹,

Schofield²

2016

Clinical Applications of Mass Spectrometry in Biomolecular Analysis

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Patients with significant proteinuria represent a unique population with respect to vitamin D status due to the urinary losses of vitamin D-binding protein (DBP) to which >99 % of circulating 25-hydroxy vitamin D (25(OH)D) is bound. Low serum concentrations of 25(OH)D have been found in children and adults with nephrotic syndrome (NS). However, previously described assays developed to quantify the magnitude of urinary loss are technically challenging. This chapter describes a simple and sensitive method to quantify 25(OH)D2 and 25(OH)D3 in urine specimens in a single analytical LC-MS/MS analysis. This assay is more sensitive than previously described radioimmunoassays and offers the ability to quantitate both forms of 25-hydroxy vitamin D. The assay involves no chemical derivitization, has a linear measurement range of 20-1500 pg/mL and displays imprecision (CVs) below 7 % at various concentrations across the analytical measurement range.

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Bone histology in steroid-treated children with non-azotemic nephrotic syndrome

Freundlich

Jofe

Goodman

et al. 2004

Pediatric Nephrology

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Patients with nephrotic syndrome (NS) and normal glomerular filtration rate (GFR) frequently exhibit abnormalities of calcium and vitamin D homeostasis, mainly hypocalcemia and reduced circulating vitamin D metabolites. These abnormalities have been linked to alterations of bone histology in adults with non-azotemic NS, particularly osteomalacia and excessive bone resorption. Whether similar abnormalities of bone histology occur in children and adolescents with NS, particularly in those requiring prolonged treatment with corticosteroids, remains largely unknown. Thus, bone histomorphometry and selected bone-modulating hormones were studied in eight children (aged 2-16 years) with normal GFR (range 85-169 ml/min per 1.73 m(2)) and NS. All patients received corticosteroids for at least 12 months prior to bone biopsy. At the time of bone biopsy, the urine protein/creatinine ratio was elevated (2.1+/-3.6), while the average concentrations of parathyroid hormone (36+/-13 pg/ml), 25-hydroxyvitamin D [25(OH) D] (22+/-14 ng/ml), and 1,25(OH)(2)D (59+/-22 pg/ml) were normal. Bone histomorphometry displayed focal osteomalacia (OM) and mild increased bone resorption in most patients. The mineralization lag time, an indicator of the degree of osteomalacia, correlated with the time elapsed since the original diagnosis of NS ( r=0.93, P<0.0005). Overt hyperparathyroidism was not evident, but increased eroded perimeter and elevated bone formation rate (BFR) were evident in two patients, suggesting high-turnover bone disease. The BFR was inversely correlated with the administered dose of prednisone at the time of biopsy ( r=-0.78, P<0.05) and one patient exhibited low bone turnover changes. The growth velocity standard deviation score (SDS) at time of biopsy ranged from -1.6 to 3.2, resulting in a height SDS range of -1.9 to 0.6. The height SDS at time of bone biopsy correlated inversely with the dose of administered glucocorticoid ( r=-0.71, P<0.05) and with the duration of the disease ( r=-0.7, P=0.05). These data, albeit preliminary, demonstrate that children with NS treated with prolonged corticosteroid therapy exhibit bone histopathological changes without a concomitant impairment in GFR. While the OM appears to be related to the disease process, the alterations of bone formation and the adynamic changes are likely the result of the corticosteroid therapy. The potential consequences of these findings on adult bone mass and ultimate height deserve further studies.

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Bone histology in patients with nephrotic syndrome and normal renal function

Abstract: OSM is a frequent finding in adult patients with NS, even at a normal level of renal function. Its severity correlates with the amount and duration of proteinuria.

Cited by 46 publications

References 18 publications

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

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

Quantitation of 25-OH-Vitamin-D2 and 25-OH-Vitamin-D3 in Urine Using LC-MS/MS

Bone histology in steroid-treated children with non-azotemic nephrotic syndrome

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