Nonparathyroid hormone-mediated calcium resorption in a rat model of immune glomerulonephritis.
Skeletal demineralization is a frequent accompaniment of chronic renal disease and is likely multifactorial. We studied the role of inflammation in stimulating bone resorption in a rat model of glomerulonephritis (GN). Three-week-old Sprague-Dawley rats received either saline (n = 8) or horse spleen apoferritin and lipopolysaccharide (HSA/LPS, n = 8) by intraperitoneal injection, for 6 weeks; afterward, they were observed for either an additional 3 weeks (9 weeks total; n = 4 from each group) or 14 weeks (20 weeks total; n = 4 from each group). Kidneys were analyzed by histomorphometry, and blood and urine samples were obtained to assess bone resorption. Whole-body and isolated femur Dual-Energy X-ray Absorptiometry (DEXA) scans were performed at the end of each study. HSA/LPS-treated animals developed a proliferative GN by 9 weeks, which is associated with proteinuria but no change in renal function. Between 9 and 20 weeks, there was evidence of an increasing interstitial inflammation (1381 +/- 67 interstitial cells/mm(2) at 9 weeks and 1818 +/- 28 interstitial cells/mm(2) at 20 weeks.) There was also evidence of bone resorbing activity as assessed by experimental/control (E/C) < 1.0 at 9 (E/C plasma = 0.66 +/- 0.05) and 20 (E/C plasma = 0.52 +/- 0.04) weeks. Parathyroid hormone (PTH) levels were normal at all time points, and no differences in bone mineral density were found. This model produces not only an immune glomerular/tubular injury, but also a stimulus for bone resorption that is related to objective measures of inflammation severity. The bone resorption is not caused by renal insufficiency, hyperparathyroidism, or steroid therapy. This model will prove useful in other studies of the role of renal inflammation in skeletal disorders.
Welch
Thomas R
TR
Department of Pediatrics, State University of New York Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. welcht@upstate.edu
Blystone
Lisa W
LW
Bergstrom
William H
WH
D000818:Animals; D015519:Bone Density; D001862:Bone Resorption / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002118:Calcium