培哚普利或硝苯地平对2型糖尿病合并微量白蛋白尿的非高血压患者的长期肾脏保护作用。

Long-term renoprotection by perindopril or nifedipine in non-hypertensive patients with Type 2 diabetes and microalbuminuria.

作者信息

Jerums G, Allen T J, Campbell D J, Cooper M E, Gilbert R E, Hammond J J, O'Brien R C, Raffaele J, Tsalamandris C

机构信息

Department of Medicine, University of Melbourne, and Endocrinology Unit, Austin Health, Studley Road, Heidelberg, 3084 Victoria, Australia.

出版信息

Diabet Med. 2004 Nov;21(11):1192-9. doi: 10.1111/j.1464-5491.2004.01316.x.

DOI:10.1111/j.1464-5491.2004.01316.x

PMID:15498085

Abstract

AIMS

To assess the efficacy of an angiotensin converting enzyme (ACE) inhibitor (perindopril), a dihydropyridine calcium channel blocker (sustained release nifedipine) and placebo in preventing the progression of albuminuria and decline in glomerular filtration rate (GFR) in patients with Type 2 diabetes and microalbuminaria.

METHODS

A prospective, randomized, open, blinded end point study of 77 patients allocated to three treatment groups (23 perindopril, 27 nifedipine, 27 placebo). Drug doses were adjusted to achieve a decrease in diastolic blood pressure (DBP) of 5 mmHg in the first 3 months and additional therapy was given if hypertension developed (supine DBP > 90 mmHg and/or systolic blood pressure (SBP) > 140 mmHg if < or = 40 years; supine DBP > 90 mmHg and/or SBP > 160 mmHg if > 40 years). Median follow-up was 66 months, with 37 patients being followed for at least 6 years.

RESULTS

Blood pressure remained within the non-hypertensive range in 83% of perindopril-, 95% of nifedipine- and 30% of placebo-treated patients (P < 0.01). In the first 12 months albumin excretion rate (AER) decreased by 47% only in the perindopril group (P = 0.04). From 12 to 72 months, AER gradients increased by 27% per year only in the placebo group (P < 0.01). After 6 years, macroalbuminuria had developed in 7/15 placebo compared with 2/11 in perindopril and 1/11 nifedipine-treated patients (P = 0.05). GFR did not change in the first 12 months, but thereafter the median GFR gradient (ml/min/1.73 m(2) per year) was -2.4 (P < 0.01) for perindopril-, -1.3 (P = 0.26) for nifedipine- and -4.2 (P = 0.01) for placebo-treated patients. The rate of decline in GFR for the study group as a whole from 12 months to the end of follow-up correlated negatively with mean arterial pressure (MAP) (r = -0.38, P < 0.01). During a 3-month treatment pause in 29 patients AER tended to increase only in the perindopril group (P < 0.07).

CONCLUSIONS

Long-term control of blood pressure with perindopril or nifedipine stabilizes AER and attenuates GFR decline in proportion to MAP in non-hypertensive patients with Type 2 diabetes and microalbuminuria.

摘要

目的

评估血管紧张素转换酶（ACE）抑制剂（培哚普利）、二氢吡啶类钙通道阻滞剂（缓释硝苯地平）及安慰剂对2型糖尿病合并微量白蛋白尿患者预防蛋白尿进展和肾小球滤过率（GFR）下降的疗效。

方法

一项前瞻性、随机、开放、盲终点研究，77例患者被分配至三个治疗组（23例用培哚普利，27例用硝苯地平，27例用安慰剂）。调整药物剂量以使舒张压（DBP）在前3个月降低5 mmHg，若发生高血压则给予额外治疗（年龄≤40岁时，仰卧位DBP>90 mmHg和/或收缩压（SBP）>140 mmHg；年龄>40岁时，仰卧位DBP>90 mmHg和/或SBP>160 mmHg）。中位随访时间为66个月，37例患者至少随访6年。

结果

培哚普利治疗组83%、硝苯地平治疗组95%、安慰剂治疗组30%的患者血压维持在非高血压范围内（P<0.01）。在最初12个月，仅培哚普利组白蛋白排泄率（AER）下降了47%（P=0.04）。从12个月至72个月，仅安慰剂组AER梯度每年增加27%（P<0.01）。6年后，安慰剂组15例中有7例出现大量蛋白尿，培哚普利组11例中有2例，硝苯地平治疗组11例中有1例（P=0.05）。GFR在最初12个月未发生变化，但此后培哚普利治疗组的中位GFR梯度（ml/min/1.73 m²每年）为-2.4（P<0.01），硝苯地平治疗组为-1.3（P=0.26），安慰剂治疗组为-4.2（P=0.01）。从12个月至随访结束，整个研究组GFR下降速率与平均动脉压（MAP）呈负相关（r=-0.38，P<0.01）。在29例患者为期3个月的治疗中断期间，仅培哚普利组AER有升高趋势（P<0.07）。