title: Adverse effects of hyperphosphatemia on myocardial hypertrophy, renal function, and bone in rats with renal failure.
abstract: BACKGROUND
  Hyperphosphatemia and disturbances in calcium or parathyroid hormone (PTH) metabolism contribute to the high incidence of cardiovascular disease and renal osteodystrophy in chronic renal failure (CRF). We evaluated the effect of hyperphosphatemia on the cardiovascular system, on renal function, and on bone in experimental uremia.
  
  
  METHODS
  Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx) with minipump implantation, delivering 1-34 rat PTH (physiologic rate), or were sham-operated and received vehicle. Only phosphorus content (low-phosphorus (LP) 0.2%; high-phosphorus (HP) 1.2%) differentiated diets. We divided the groups as follows: PTx +Nx +LP; sham + LP; PTx + Nx + HP; and sham + HP. Tail-cuff pressure and weight were measured weekly. After 2 months, biochemical, arterial, and myocardial histology and bone histomorphometry were analyzed.
  
  
  RESULTS
  Heart weight normalized to body weight (heart weight/100 g body weight) was higher in PTx + Nx + HP rats (PTx + Nx + HP = 0.36 +/- 0.01 vs. sham + HP = 0.29 +/- 0.01, PTx + Nx + LP = 0.32 +/- 0.01, sham + LP = 0.28 +/- 0.01) (P < 0.05). Serum creatinine levels were higher in PTx + Nx + HP rats than in PTx + Nx + LP rats (1.09 +/- 0.13 vs. 0.59 +/- 0.03 mg/dL) (P < 0.05). Levels of PTH did not differ significantly between the groups. Myocardial and arterial histology detected no vascular calcification or fibrosis. Bone histomorphometry revealed an association, unrelated to uremia, between HP diets and decreased trabecular connectivity.
  
  
  CONCLUSIONS
  Myocardial hypertrophy, impaired renal function, and adverse effects on bone remodeling were associated with hyperphosphatemia and were not corrected by PTH replacement. Although no vascular calcification was observed in this model, we cannot rule out an adverse effect of hyperphosphatemia on the vascular bed. Our finding underscores the importance of phosphorus control in reducing morbidity and mortality in CRF patients.
authors.affiliation: Nephrology and Pathology Division, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Katia R
authors.initials: KR
authors.lastname: Neves
authors.forename: Fabiana G
authors.initials: FG
authors.lastname: Graciolli
authors.forename: Luciene M
authors.initials: LM
authors.lastname: dos Reis
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Pasqualucci
authors.forename: Rosa M A
authors.initials: RM
authors.lastname: Moysés
authors.forename: Vanda
authors.initials: V
authors.lastname: Jorgetti
mesh_terms: D000818:Animals; D001835:Body Weight; D001842:Bone and Bones / Q000473:pathology; D006332:Cardiomegaly / Q000097:blood / Q000150:complications* / Q000473:pathology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood / Q000150:complications* / Q000473:pathology; D004435:Eating; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000150:complications* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D010758:Phosphorus / Q000097:blood; D010760:Phosphorus Metabolism Disorders / Q000097:blood / Q000150:complications* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010758:Phosphorus