Hafez K S, Inman S R, Stowe N T, Novick A C
Department of Urology, Cleveland Clinic Foundation, Ohio 44195, USA.
Urology. 1996 Dec;48(6):862-7. doi: 10.1016/s0090-4295(96)00314-7.
Patients with renal mass reduction of more than 50% are at increased risk for progressive renal failure. Lipid-lowering agents have been shown to preserve renal function in various models of chronic renal failure. This study was performed to evaluate the hemodynamic effects of lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in the remnant kidney model.
Two groups of animals were studied. Group 1 (n = 9) served as controls and group 2 (n = 14) received lovastatin, 15 mg/kg/day orally, for 2 weeks after renal ablation. Glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, ultrasonic flow probe), and 24-hour protein excretion were measured in anesthetized rats.
Two weeks after renal ablation, GFR was 0.28 +/- 0.09 mL/min/gkw (gram kidney weight) in group 1, whereas in group 2, lovastatin preserved GFR at 0.58 +/- 0.3 mL/min/gkw (P < 0.05). RBF in group 1 was 1.2 +/- 0.2 mL/min/gkw and increased to 2.1 +/- 0.4 mL/min/gkw in group 2 (P < 0.05), representing a 43% increase. Protein excretion decreased significantly to 13 +/- 1.7 mg/24 hr in group 2. The lovastatin-treated group had a lower serum cholesterol (59 +/- 3 mg/dL versus 71 +/- 2 mg/dL, P < 0.05), but serum triglyceride levels were not different between the two groups.
Lovastatin preserves renal function in a renal ablation model after 2 weeks of treatment. It specifically increased total RBF. Therefore, in addition to its known cholesterol lowering effect, lovastatin also has the direct renal hemodynamic effect of increasing RBF and maintaining GFR.
肾质量减少超过50%的患者发生进行性肾衰竭的风险增加。在各种慢性肾衰竭模型中,降脂药物已被证明可保护肾功能。本研究旨在评估3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂洛伐他汀在残余肾模型中的血流动力学效应。
对两组动物进行研究。第1组(n = 9)作为对照组,第2组(n = 14)在肾切除术后口服洛伐他汀,剂量为15 mg/kg/天,持续2周。在麻醉的大鼠中测量肾小球滤过率(GFR,菊粉清除率)、肾血流量(RBF,超声血流探头)和24小时蛋白排泄量。
肾切除术后2周,第1组的GFR为0.28±0.09 mL/min/gkw(克肾重),而在第2组中,洛伐他汀使GFR维持在0.58±0.3 mL/min/gkw(P < 0.05)。第1组的RBF为1.2±0.2 mL/min/gkw,第2组增加到2.1±0.4 mL/min/gkw(P < 0.05),增加了43%。第2组的蛋白排泄量显著降低至13±1.7 mg/24小时。洛伐他汀治疗组的血清胆固醇较低(59±3 mg/dL对71±2 mg/dL,P < 0.05),但两组的血清甘油三酯水平无差异。
洛伐他汀在治疗2周后的肾切除模型中可保护肾功能。它特异性地增加了总肾血流量。因此,除了已知的降胆固醇作用外,洛伐他汀还具有增加肾血流量和维持肾小球滤过率的直接肾血流动力学效应。