Reversal of the adynamic bone disorder and decreased vascular calcification in chronic kidney disease by sevelamer carbonate therapy.
A model of chronic kidney disease (CKD)-induced vascular calcification (VC) that complicates the metabolic syndrome was produced. In this model, the metabolic syndrome is characterized by severe atherosclerotic plaque formation, hypertension, type 2 diabetes, obesity, and hypercholesterolemia, and CKD stimulates calcification of the neointima and tunica media of the aorta. The CKD in this model is associated the adynamic bone disorder form of renal osteodystrophy. The VC of the model is associated with hyperphosphatemia, and control of the serum phosphorus both in this animal model and in humans has been preventive in the development of VC. This article reports studies that demonstrate reduction of established VC by the addition of sevelamer carbonate to the diets of this murine metabolic syndrome model with CKD. Sevelamer, besides normalizing the serum phosphorus, surprisingly, reversed the CKD-induced trabecular osteopenia. Sevelamer therapy increased osteoblast surfaces in the metaphyseal trabeculae of the tibia and femur. It also increased osteoid surfaces and, importantly, bone formation rates. In addition, sevelamer was found to be effective in decreasing serum cholesterol levels. These results suggest that sevelamer may have important actions in decreasing diabetic and uremic vasculopathy and that sevelamer carbonate may be capable of increasing bone formation rates that are suppressed by diabetic nephropathy.
Mathew
Suresh
S
Renal Division, Department of Pediatrics, Washington University School of Medicien, St. Louis, Missouri 63110, USA.
Lund
Richard J
RJ
Strebeck
Frank
F
Tustison
Kimberly S
KS
Geurs
Theresa
T
Hruska
Keith A
KA
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000473:pathology*; D001847:Bone Diseases / Q000188:drug therapy* / Q000209:etiology*; D002114:Calcinosis / Q000188:drug therapy* / Q000209:etiology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000188:drug therapy / Q000209:etiology; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010012:Osteogenesis / Q000187:drug effects; D011073:Polyamines / Q000627:therapeutic use*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D000069603:Sevelamer
D004041:Dietary Fats; D011073:Polyamines; D011973:Receptors, LDL; D000069603:Sevelamer