Kanno Yoshihiko, Takenaka Tsuneo, Nakamura Tsukasa, Suzuki Hiromichi
Department of Nephrology, Saitama Medical School, 38 Morohongo, Moroyama, Iruma, Saitama, 350-0495 Japan.
Clin J Am Soc Nephrol. 2006 Jul;1(4):730-7. doi: 10.2215/CJN.01110905. Epub 2006 May 17.
The benefit of the add-on angiotensin II receptor blocker candesartan to angiotensin-converting enzyme (ACE) inhibitors in inhibition of progression of nephropathy in hypertensive patient with nondiabetic renal disease compared with monotherapy with ACE inhibitors remains controversial. All patients were previously treated with ACE inhibitors. Urinary protein excretion of patients exceeded 1.0 g/d despite treatment with ACE inhibitors. Ninety hypertensive patients with chronic renal insufficiency were randomly assigned to one of two groups. One group received ACE inhibitor plus candesartan (2 to 12 mg/d), and a control group received only ACE inhibitor. The target BP was < or = 130/80 mmHg. The primary outcome was the changes in serum creatinine and the reduction of proteinuria. The mean duration of follow-up was 3.1 +/- 0.4 yr. At years 2 and 3, systolic and diastolic BP were reduced from 140 +/- 3/84 +/- 2 to 129 +/- 1/78 +/- 2 mmHg (candesartan group) and from 135 +/- 2/85 +/- 2 to 130 +/- 2/80 +/- 2 mmHg (ACE inhibitors group). In both groups, both systolic and diastolic BP decreased significantly from the beginning to the end of the study (P < 0.01). The serum creatinine concentration increased from 3.02 +/- 0.27 to 3.38 +/- 0.49 mg/dl (candesartan plus ACE inhibitor group) versus 3.00 +/- 0.37 to 4.48 +/- 0.57 mg/dl (ACE inhibitor group; P < 0.01) at year 3. Although the level of proteinuria significantly declined in each group (P < 0.05), the degree of reductions in proteinuria was greater in the candesartan group than in the ACE inhibitors group (P < 0.01). In the patients who were treated with candesartan and ACE inhibitor or ACE inhibitor alone, pretreatment proteinuria correlated significantly with decline of renal function, whereas reduction of proteinuria negatively correlated with decline in renal function in the patients who were treated with candesartan. Candesartan with an ACE inhibitor is effective in slowing the progression of renal insufficiency in hypertensive patients with nondiabetic renal disease through reduction of proteinuria.
与单用血管紧张素转换酶（ACE）抑制剂相比，在非糖尿病肾病高血压患者中，加用血管紧张素II受体阻滞剂坎地沙坦对抑制肾病进展的益处仍存在争议。所有患者之前均接受过ACE抑制剂治疗。尽管接受了ACE抑制剂治疗，但患者的尿蛋白排泄量仍超过1.0g/d。90例慢性肾功能不全的高血压患者被随机分为两组。一组接受ACE抑制剂加坎地沙坦（2至12mg/d），对照组仅接受ACE抑制剂。目标血压为≤130/80mmHg。主要结局是血清肌酐的变化和蛋白尿的减少。平均随访时间为3.1±0.4年。在第2年和第3年，收缩压和舒张压从140±3/84±2降至129±1/78±2mmHg（坎地沙坦组），从135±2/85±2降至130±2/80±2mmHg（ACE抑制剂组）。在两组中，收缩压和舒张压从研究开始到结束均显著下降（P<0.01）。在第3年，血清肌酐浓度从3.02±0.27升至3.38±0.49mg/dl（坎地沙坦加ACE抑制剂组），而在ACE抑制剂组中从3.00±0.37升至4.48±0.57mg/dl（P<0.01）。尽管每组蛋白尿水平均显著下降（P<0.05），但坎地沙坦组蛋白尿减少程度大于ACE抑制剂组（P<0.01）。在接受坎地沙坦和ACE抑制剂或单用ACE抑制剂治疗的患者中，治疗前蛋白尿与肾功能下降显著相关，而在接受坎地沙坦治疗的患者中，蛋白尿减少与肾功能下降呈负相关。坎地沙坦与ACE抑制剂联合使用可通过减少蛋白尿有效减缓非糖尿病肾病高血压患者肾功能不全的进展。
