Bone histology in patients with nephrotic syndrome and normal renal function

Background The prevalence of metabolic bone disease in patients with nephro tic syndrome (NS) at normal level of renal function remains uncertain. Methods. To address this issue, we studied 30 patients (20 men and 10 women , mean age 27.3 +/- 11.7 years) with NS who had normal renal function (mean creatinine clearance 103 +/- 4 ml/min). We evaluated their serum calcium, phosphorus, alkaline phosphatase, immunoreactive parathyroid hormone (iPTH) , vitamin D metabolites, urinary calcium, and skeletal survey. The extent o f bone mineralization was analyzed by histomorphometric analysis of iliac c rest bone biopsy specimens in all patients. The findings on bone histology were correlated with biochemical parameters. Results. The mean duration of NS was 35.5 +/- 26.9 months, with a protein e xcretion of 7.3 +/- 3.2 g/24 hr and a serum albumin of 2.2 +/- 0.8 g/dl. To tal serum calcium was 7.8 +/- 0.8 mg/dl, whereas ionized calcium was 5.7 +/ - 0.7 mg/dl, phosphorus 3.2 +/- 1.2 mg/dl, and alkaline phosphatase 149 +/- 48.6 Uniter. Serum iPTH levels were normal in all except two patients. The mean serum 25-hydroxyvitamin D [25(OH)D] level was 3.9 +/- 1.2 ng/ml (norm al 15 to 30 ng/ml), whereas 1,25-dihydroxyvitamin D was 24 +/- 4.7 pg/ml (n ormal 16 to 65). There was an inverse correlation between serum levels of 2 5(OH)D and the magnitude of proteinuria (r = -0.42, P < 0.05). The mean 24- hour urinary calcium excretion was 82 +/- 21 mg/day. The skeletal survey wa s normal in all patients. Bone histology was normal in 33.3 % of the patien ts, whereas 56.7 % had isolated osteomalacia (OSM), and 10% had an increase d bone resorption in association with defective mineralization. The severit y of OSM measured by mineralization lag time correlated linearly with the d uration (r = 0.94, P < 0.0001) and the amount (r = 0.97, P < 0.0001) of pro teinuria. All patients with NS for more than three years had histological c hanges. Patients with OSM had lower 25(OH)D and serum albumin as compared w ith those with normal histology (P < 0.005). Bone mineralization had no sig nificant correlation with serum iPTH, divalent ions, or vitamin D levels. Conclusions. OSM is a frequent finding in adult patients with NS, even at a normal level of renal function. Its severity correlates with the amount an d duration of proteinuria.