Neves Katia R, Graciolli Fabiana G, dos Reis Luciene M, Pasqualucci Carlos A, Moysés Rosa M A, Jorgetti Vanda
Nephrology and Pathology Division, University of São Paulo, São Paulo, SP, Brazil.
Kidney Int. 2004 Dec;66(6):2237-44. doi: 10.1111/j.1523-1755.2004.66013.x.
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.
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.
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.
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.
高磷血症以及钙或甲状旁腺激素（PTH）代谢紊乱是导致慢性肾衰竭（CRF）患者心血管疾病和肾性骨营养不良高发的原因。我们评估了高磷血症对实验性尿毒症大鼠心血管系统、肾功能及骨骼的影响。
将Wistar大鼠进行甲状旁腺切除术（PTx）和5/6肾切除术（Nx）并植入微型泵，输注1-34大鼠PTH（生理速率），或进行假手术并给予赋形剂。仅通过磷含量（低磷（LP）0.2%；高磷（HP）1.2%）区分饮食。我们将大鼠分为以下几组：PTx + Nx + LP；假手术 + LP；PTx + Nx + HP；假手术 + HP。每周测量尾袖血压和体重。2个月后，分析生化指标、动脉和心肌组织学以及骨组织形态计量学。
PTx + Nx + HP组大鼠的心脏重量与体重之比（心脏重量/100 g体重）高于其他组（PTx + Nx + HP = 0.36 ± 0.01，假手术 + HP = 0.29 ± 0.01，PTx + Nx + LP = 0.32 ± 0.01，假手术 + LP = 0.28 ± 0.01）（P < 0.05）。PTx + Nx + HP组大鼠的血清肌酐水平高于PTx + Nx + LP组大鼠（1.09 ± 0.13 vs. 0.59 ± 0.03 mg/dL）（P < 0.05）。各组间PTH水平无显著差异。心肌和动脉组织学检查未发现血管钙化或纤维化。骨组织形态计量学显示，高磷饮食与小梁连接性降低有关，且与尿毒症无关。
心肌肥大、肾功能受损以及对骨重塑的不良影响与高磷血症相关，且甲状旁腺激素替代治疗无法纠正这些影响。尽管在该模型中未观察到血管钙化，但我们不能排除高磷血症对血管床的不良影响。我们的研究结果强调了控制磷对降低CRF患者发病率和死亡率的重要性。
