Rysavá Romana, Tesar Vladimír, Merta Miroslav
Department of Nephrology, 1st School of Medicine and General Faculty Hospital, Charles University, Prague, Czech Republic.
Blood Press Monit. 2005 Aug;10(4):207-13. doi: 10.1097/01.mbp.0000172708.97534.15.
To assess the antihypertensive and antiproteinuric efficacy and safety of the angiotensin II type 1 receptor blocker telmisartan in patients with hypertension and chronic kidney disease.
A multicenter, prospective trial was performed in adults with hypertension [systolic blood pressure (SBP)/diastolic blood pressure (DBP) >130/85 mmHg), chronic renal insufficiency (serum creatinine <4.0 mg/dl), and proteinuria (>1 g/24 h). In addition to existing antihypertensive therapy, the nature and doses of which remained unchanged throughout the study, patients received once-daily telmisartan 40 mg for the first 3 months followed by forced titration to telmisartan 80 mg for the subsequent 3 months to achieve a target SBP/DBP of <130/85 mmHg. The rationale for using telmisartan was its long half-life efficacy, greater antihypertensive effect compared with valsartan or losartan, and newly discovered potential antidiabetic effect.
The study was conducted in 92 patients (45 men, 47 women), of whom 60 had diabetes mellitus (54 patients with type 2 disease). Five patients discontinued prematurely: two because of hyperkalemia, two because of protocol violation, and one because of lack of efficacy. After 6 months' telmisartan treatment, office trough seated SBP was reduced by 19.6 mmHg (P<0.001) from 154.9+/-14.6 mmHg and DBP by 11.8 mmHg (P<0.001) from 91.7+/-8.1 mmHg. Seated trough SBP/DBP of <130/85 mmHg was achieved at 6 months in 34.8% of patients. Ambulatory blood pressure monitoring also demonstrated significant reductions in mean daytime SBP of 10.9 mmHg (P=0.01), night-time SBP of 12.1 mmHg (P=0.05), daytime DBP of 3.1 mmHg (P=0.05), and night-time DBP of 6.5 mmHg (P=0.05). Proteinuria decreased significantly from 3.6+/-3.4 to 2.8+/-2.8 g/24 h (P=0.01). A decrease in proteinuria depended significantly on a decrease in SBP at the end of the study (P=0.044). Each decrease in SBP of about 10 mmHg led to a decrease in proteinuria of about 0.79 g/24 h (95% CI 0.02-1.56 g/24 h). Serum creatinine increased from 1.96+/-0.79 to 2.08+/-0.89 mg/dl (P=0.01), whereas creatinine clearance did not change significantly.
Telmisartan effectively and safely reduced blood pressure and brought about regression of proteinuria in diabetic and nondiabetic, hypertensive, proteinuric patients with chronic kidney disease, even in those with mild-to-moderate chronic renal failure.
评估1型血管紧张素II受体阻滞剂替米沙坦对高血压合并慢性肾病患者的降压、降蛋白尿疗效及安全性。
对患有高血压（收缩压/舒张压>130/85 mmHg）、慢性肾功能不全（血清肌酐<4.0 mg/dl）及蛋白尿（>1 g/24 h）的成年人进行一项多中心前瞻性试验。除了在整个研究过程中保持不变的现有降压治疗外，患者在最初3个月每天服用一次40 mg替米沙坦，随后3个月强制滴定至80 mg替米沙坦，以实现收缩压/舒张压目标<130/85 mmHg。使用替米沙坦的理由是其半衰期长、疗效好，与缬沙坦或氯沙坦相比具有更强的降压作用，以及新发现的潜在抗糖尿病作用。
该研究纳入了92例患者（45例男性，47例女性），其中60例患有糖尿病（54例为2型糖尿病）。5例患者提前停药：2例因高钾血症，2例因违反方案，1例因无效。替米沙坦治疗6个月后，诊室静息收缩压从154.9±14.6 mmHg降至135.3 mmHg（降低19.6 mmHg，P<0.001），舒张压从91.7±8.1 mmHg降至79.9 mmHg（降低11.8 mmHg，P<0.001）。34.8%的患者在6个月时达到静息收缩压/舒张压<130/85 mmHg。动态血压监测也显示白天平均收缩压显著降低10.9 mmHg（P=0.01），夜间收缩压降低12.1 mmHg（P=0.05），白天舒张压降低3.1 mmHg（P=0.05），夜间舒张压降低6.5 mmHg（P=0.05）。蛋白尿从3.6±3.4 g/24 h显著降至2.8±2.8 g/24 h（P=0.01）。蛋白尿的降低在研究结束时显著依赖于收缩压降低（P=0.044）。收缩压每降低约10 mmHg导致蛋白尿降低约0.79 g/24 h（95%可信区间0.02 - 1.56 g/24 h）。血清肌酐从1.96±0.79 mg/dl升至2.08±0.89 mg/dl（P=0.01），而肌酐清除率无显著变化。
替米沙坦有效且安全地降低了糖尿病和非糖尿病、高血压、蛋白尿性慢性肾病患者的血压，并使蛋白尿减轻，即使是轻度至中度慢性肾衰竭患者。
