Weinberg Adam J, Zappe Dion H, Ramadugu Rajeev, Weinberg Marc S
College of Arts and Sciences, Boston University, Boston, Massachusetts, USA.
J Hypertens Suppl. 2006 Mar;24(1):S95-9. doi: 10.1097/01.hjh.0000220413.22482.36.
Reducing urinary protein excretion in patients with renal disease is an important therapeutic target to prevent the progression of renal and cardiovascular disease. Drugs such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARBs), which block the actions of the renin-angiotensin-aldosterone system, are recommended because they reduce blood pressure and proteinuria. Recently, the use of higher doses of ARBs, up to three times the maximal approved dose, resulted in further reductions in protein excretion. Despite the effectiveness of this therapeutic approach, no long-term safety analysis has been conducted in patients receiving high-dose ARB treatment.
To study the long-term safety of high-dose ARB treatment.
We observed 48 patients [44 men and 4 women; ages 64 +/- 15 years (mean +/- SD), weight 88 +/- 28 kg, estimated glomerular filtration rate 53 +/- 23 ml/min] receiving treatment with high doses (1.5-5 times greater than the maximum approved dose) of ARBs, for 40 +/- 24 months (range 6-98 months).
The average ARB dose tended to increase over time and was 3.2 +/- 1.2 times greater at the end of the study than that at the start. Systolic blood pressure was similar at the beginning and end of the study period (132 +/- 20 and 125 +/- 20 mmHg, respectively), but diastolic blood pressure showed a decrease throughout the study and was significantly reduced (P < 0.05) in association with 1.5x and 2x the maximum ARB dose (73 +/- 11 and 72 +/- 10 mmHg, respectively) when compared with baseline (78 +/- 11 mm Hg). There was a trend (P > 0.05) for increases in concentrations of serum potassium (0.2 +/- 0.9 mmol/l) and creatinine (0.3 +/- 0.7 mg/dl) with increases in dose from baseline to the end of the study. Serum creatinine concentration was greater (P < 0.05) at the periods of 3x and 4x the maximum dose, but this represented increases of only 12 and 20% from baseline, respectively.
High-dose ARB treatment in patients with chronic renal disease is not associated with any clinically significant long-term negative effects on serum creatinine or potassium and is thus a important therapeutic modality with which to achieve further reductions in urinary protein excretion.
降低肾病患者的尿蛋白排泄是预防肾脏和心血管疾病进展的重要治疗目标。推荐使用诸如血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂（ARBs）等药物，这些药物可阻断肾素 - 血管紧张素 - 醛固酮系统的作用，因为它们可降低血压和蛋白尿。最近，使用高达最大批准剂量三倍的高剂量ARBs可进一步降低蛋白排泄。尽管这种治疗方法有效，但尚未对接受高剂量ARB治疗的患者进行长期安全性分析。
研究高剂量ARB治疗的长期安全性。
我们观察了48例患者[44例男性和4例女性；年龄64±15岁（均值±标准差），体重88±28 kg，估计肾小球滤过率53±23 ml/min]，他们接受高剂量（比最大批准剂量大1.5 - 5倍）的ARBs治疗40±24个月（范围6 - 98个月）。
平均ARB剂量随时间有增加趋势，在研究结束时比开始时大3.2±1.2倍。收缩压在研究开始和结束时相似（分别为132±20和125±20 mmHg），但舒张压在整个研究过程中呈下降趋势，与最大ARB剂量的1.5倍和2倍相关时显著降低（P < 0.05）（分别为73±11和72±10 mmHg），与基线（78±11 mmHg）相比。从基线到研究结束，随着剂量增加，血清钾（0.2±0.9 mmol/l）和肌酐（0.3±0.7 mg/dl）浓度有增加趋势（P > 0.05）。血清肌酐浓度在最大剂量的3倍和4倍时更高（P < 0.05），但分别仅比基线增加12%和20%。
慢性肾病患者的高剂量ARB治疗对血清肌酐或钾没有任何临床上显著的长期负面影响，因此是实现进一步降低尿蛋白排泄的重要治疗方式。
