Bailey R R, Shand B I, Smith A H, Robson R A, Lynn K L
Department of Nephrology, Christchurch Hospital, New Zealand.
Clin Nephrol. 1997 Oct;48(4):224-9.
There are few studies on the use of dihydropyridine calcium antagonists in hypertensive patients with moderate renal insufficiency. We undertook an open study on the effects on renal function, albumin excretion and blood pressure of the slow-onset, long-acting dihydropyridine calcium antagonist, lacidipine, in 14 patients with stable, chronic renal insufficiency (mean assessed GFR 0.78 ml/s, range 0.50-1.17 ml/s) and moderate hypertension. Following a 2 week washout phase, lacidipine was administered for 24 weeks in a dose of 2 mg/day with the dose being titrated at 2 weekly intervals to a maximum of 6 mg/day in order to achieve adequate blood pressure control. Frusemide was introduced if blood pressure was not controlled on the maximum lacidipine dose. Blood pressure, creatinine clearance, 24 h urinary albumin excretion and plasma creatinine and albumin concentrations were measured at regular intervals throughout the study. Isotopic GFR was determined at the end of the washout period and at week 24. Lacidipine was not very effective in controlling blood pressure and had an adverse effect on renal function. In 3 patients with an incipient nephrotic syndrome this necessitated withdrawal from the study. Mean GFR of the 10 patients who completed the study decreased from 0.69 ml/s/1.73 m2 at baseline to 0.56 ml/s/1.73 m2 at week 24 (p = 0.006) with a decline in GFR being observed in 9 of these patients. The decrease in GFR was greatest in patients with poorly controlled blood pressure. An insignificant increase in mean urinary albumin excretion occurred during the study with this increase being observed only in patients with albuminuria > 1 g/24 h at baseline. These findings indicated that systemic hypertension altered glomerular hemodynamics and that the vasodilatation of pre-glomerular vessels which followed introduction of the calcium antagonist may have exacerbated this situation. The withdrawal of an angiotensin converting enzyme inhibitor during the washout period may have contributed to these changes. We suggest that renal function should be monitored closely in patients with renal insufficiency when a calcium antagonist is being used to control blood pressure, particularly in those with either marginal blood pressure control, significant albuminuria or an incipient nephrotic syndrome.
关于二氢吡啶类钙拮抗剂在中度肾功能不全高血压患者中的应用研究较少。我们对14例稳定的慢性肾功能不全（平均评估肾小球滤过率为0.78 ml/s，范围为0.50 - 1.17 ml/s）且患有中度高血压的患者进行了一项开放研究，观察起效缓慢、作用持久的二氢吡啶类钙拮抗剂拉西地平对肾功能、白蛋白排泄及血压的影响。在为期2周的洗脱期后，给予拉西地平24周，起始剂量为2 mg/天，每2周调整一次剂量，最大剂量为6 mg/天，以实现充分的血压控制。如果在最大拉西地平剂量下血压仍未得到控制，则加用呋塞米。在整个研究过程中定期测量血压、肌酐清除率、24小时尿白蛋白排泄量以及血浆肌酐和白蛋白浓度。在洗脱期结束时和第24周测定同位素肾小球滤过率。拉西地平在控制血压方面效果不佳，且对肾功能有不良影响。在3例早期肾病综合征患者中，这导致他们退出了研究。完成研究的10例患者的平均肾小球滤过率从基线时的0.69 ml/s/1.73 m²降至第24周时的0.56 ml/s/1.73 m²（p = 0.006），其中9例患者的肾小球滤过率出现下降。肾小球滤过率下降在血压控制不佳的患者中最为明显。在研究期间，平均尿白蛋白排泄量有不显著的增加，且这种增加仅在基线时白蛋白尿>1 g/24 h的患者中观察到。这些发现表明全身性高血压改变了肾小球血流动力学，并且引入钙拮抗剂后肾小球前血管的血管舒张可能加剧了这种情况。洗脱期内停用血管紧张素转换酶抑制剂可能促成了这些变化。我们建议，当使用钙拮抗剂控制血压时，尤其是在血压控制不佳、有显著白蛋白尿或早期肾病综合征的肾功能不全患者中，应密切监测其肾功能。
