Absence of Metabolic Bone Disease in Adult Patients with the Nephrotic Syndrome and Normal Renal Function*

Abstract

Patients with the nephrotic syndrome and normal renal function have low levels of 25(OH)D in serum presumably due to the loss of this metabolite in the urine. Osteomalacia and hyperparathyroidism have been recently reported to occur as a consequence of those low levels of 25-hydroxyvitamin D (25OHD). We studied six patients (aged 26-52 yr) with the nephrotic syndrome (mean duration, 6.7 yr; range, 2-12 yr) and normal renal function, and evaluated their calcium, phosphorus, PTH, and vitamin D metabolite levels. Bone biopsies were obtained in all patients. The creatinine clearance ranged from 83-134 ml/min . 1.73 m2 of body surface, serum albumin was 2.65 +/- 0.42 (+/- SD) g/100 ml, and proteinuria ranged from 3.5-13.2 g/24 h. All patients had normal serum magnesium, phosphorus, ionized calcium, and alkaline phosphatase (total and bone fraction), and normal roentgenographic metabolic bone survey. Serum PTH, measured by the carboxy-terminal RIA, was 5.1 +/- 2.3 mu leq/ml (normal, 2-10), serum 250HD was 8.8 +/- 4.0 ng/ml (normal, 15-30), and 1,25-dihydroxyvitamin D3 was 38 +/- 25 pg/ml (normal, 17-58). Serum vitamin D-binding protein was 420 +/- 42 micrograms/ml (normal, 400-800). The histological appearance of bone biopsies obtained in these patients was not different from that in a group of sex- and age-matched controls. Specifically, there was no increase in the volume of osteoid (unmineralized bone), the percentage of trabecular surface covered by osteoid, or the number of osteoclasts. The cellular rate of mineralization was normal in all six patients. Thus, these data indicate that low serum levels of 250HD in patients with the nephrotic syndrome and normal renal function do not necessarily result in the development of osteomalacia and/or hyperparathyroidism.

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

“…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).…”

“…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).…”

“…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.…”

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

“…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.…”

“…Whilst the binding of DBP of vitamin D occurs with a K a similar to that for 1,25(OH) 2 D (2), the other hydroxylated metabolites bind to DBP with affinities that are about 100 times as high (3±5). The metabolites 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25 (OH) 2 D) circulate in blood at concentrations about 1000 times higher than those of 1,25(OH) 2 D, but because of the remarkably high concentration of DBP in relation to the vitamin D metabolites, many binding sites are still available for 1,25(OH) 2 D and the percentage of free hormone is very low (,0.1%) (6).…”