Department of Nephrology, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.
J Investig Med. 2012 Oct;60(7):1041-7. doi: 10.2310/JIM.0b013e31826741d2.
Nondiabetic chronic kidney disease (CKD) is the leading major cause of end-stage renal disease in developing countries including China. Among the 5 stages of CKD, it is critical to retard the progression of stage 3 because renal disorder could accelerate aggravation behind that stage. Data suggest that high dosages of angiotensin receptor blockers (ARBs) could retard the progression of renal disease in hypertensive and/or diabetic patients. Nevertheless, in daily practice of nephrology, quite a number of nondiabetic patients with CKD who are normotensive do not tolerate even moderate dosages of ARBs because of adverse effects such as systemic hypotension, epically for Chinese patients. The aim of this study was to investigate the renoprotective effects of relatively low dosages of ARBs in normotensive Chinese patients with nondiabetic stage 3 CKD.
A prospective, randomized, parallel-group, open-label study was performed over a period of 12 months. A total of 238 enrolled patients were randomly allocated to treatment with losartan 50 mg (n = 119) or placebo (n = 119). All patients were followed up at 2-month intervals. At each visit, blood pressure was measured, and urinalysis and serum biochemistry tests were performed.
Finally, 112 patients given losartan and 114 patients given placebo completed the study. In the losartan group, there was a significant and biphasic time-dependent decline in proteinuria during therapy (1.72 ± 0.47 to 0.99 ± 0.48 g/d; P < 0.001). Conversely, placebo did not simultaneously change the amount of proteinuria (1.73 ± 0.49 to 1.64 ± 0.50 g/d; P = 0.337). Estimated glomerular filtration rate remained stable during the entire study period in the patients given losartan (44.8 ± 8.1 to 44.1 ± 7.7 mL/min per 1.73 m; P = 0.120) but were significantly reduced in the placebo group (44.5 ± 8.5 to 39.1 ± 7.4 mL/min per 1.73 m, P < 0.001). The changes in blood pressure were kept constant in the 2 groups. All adverse events were minimal and nonfatal.
For normotensive patients with nondiabetic stage 3 CKD, therapy with a daily dose of losartan, 50 mg, may perform effective renoprotection without changing blood pressure and be generally safe and well tolerated.
非糖尿病性慢性肾病（CKD）是发展中国家（包括中国）终末期肾病的主要原因。在 CKD 的 5 个阶段中，延缓 3 期的进展至关重要，因为在该阶段之后，肾脏疾病可能会加速恶化。数据表明，大剂量血管紧张素受体阻滞剂（ARB）可延缓高血压和/或糖尿病患者的肾脏疾病进展。然而，在肾脏病学的日常实践中，相当数量的非糖尿病性 CKD 患者血压正常，但即使是中等剂量的 ARB 也无法耐受，因为会出现全身性低血压等不良反应，中国患者尤为如此。本研究旨在探讨相对低剂量 ARB 在非糖尿病性 3 期 CKD 血压正常的中国患者中的肾脏保护作用。
进行了一项为期 12 个月的前瞻性、随机、平行组、开放标签研究。共有 238 名入组患者被随机分配至接受氯沙坦 50mg 治疗（n=119）或安慰剂治疗（n=119）。所有患者均每 2 个月随访一次。每次就诊时测量血压，并进行尿分析和血清生化检查。
最终，112 名接受氯沙坦治疗的患者和 114 名接受安慰剂治疗的患者完成了研究。在氯沙坦组，治疗期间蛋白尿呈显著的双相时间依赖性下降（1.72±0.47 至 0.99±0.48g/d；P＜0.001）。相反，安慰剂组蛋白尿的量没有同时变化（1.73±0.49 至 1.64±0.50g/d；P=0.337）。在整个研究期间，接受氯沙坦治疗的患者肾小球滤过率保持稳定（44.8±8.1 至 44.1±7.7mL/min/1.73m；P=0.120），而安慰剂组则显著降低（44.5±8.5 至 39.1±7.4mL/min/1.73m，P＜0.001）。两组的血压变化保持不变。所有不良事件均轻微且非致命。
对于血压正常的非糖尿病性 3 期 CKD 患者，每日 50mg 氯沙坦治疗可能具有有效的肾脏保护作用，而不会改变血压，且通常安全且耐受良好。
