title: Bone histology in patients with nephrotic syndrome and normal renal function.
abstract: BACKGROUND
  The prevalence of metabolic bone disease in patients with nephrotic 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 of bone mineralization was analyzed by histomorphometric analysis of iliac crest 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 excretion of 7.3 +/- 3.2 g/24 hr and a serum albumin of 2.2 +/- 0.8 g/dl. Total 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 U/liter. 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 (normal 15 to 30 ng/ml), whereas 1,25-dihydroxyvitamin D was 24 +/- 4.7 pg/ml (normal 16 to 65). There was an inverse correlation between serum levels of 25(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 was normal in all patients. Bone histology was normal in 33.3% of the patients, whereas 56.7% had isolated osteomalacia (OSM), and 10% had an increased bone resorption in association with defective mineralization. The severity of OSM measured by mineralization lag time correlated linearly with the duration (r = 0.94, P < 0.0001) and the amount (r = 0.97, P < 0.0001) of proteinuria. All patients with NS for more than three years had histological changes. Patients with OSM had lower 25(OH)D and serum albumin as compared with those with normal histology (P < 0.005). Bone mineralization had no significant 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 and duration of proteinuria.
authors.affiliation: Division of Nephrology, Winthrop University Hospital, Mineola, New York, USA. Sanjeevkmittal@hotmail.com
authors.forename: S K
authors.initials: SK
authors.lastname: Mittal
authors.forename: S C
authors.initials: SC
authors.lastname: Dash
authors.forename: S C
authors.initials: SC
authors.lastname: Tiwari
authors.forename: S K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: S
authors.initials: S
authors.lastname: Saxena
authors.forename: S
authors.initials: S
authors.lastname: Fishbane
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000906:Antibodies; D001706:Biopsy; D002113:Calcification, Physiologic / Q000502:physiology; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000453:epidemiology / Q000473:pathology* / Q000503:physiopathology; D010018:Osteomalacia / Q000453:epidemiology / Q000473:pathology* / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000097:blood / Q000276:immunology; D010758:Phosphorus / Q000097:blood; D015995:Prevalence; D011507:Proteinuria / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D014810:Vitamin E / Q000097:blood
chemical_list: D000906:Antibodies; D010281:Parathyroid Hormone; D014810:Vitamin E; D010758:Phosphorus; D000469:Alkaline Phosphatase; D002118:Calcium