Buter H, Hemmelder M H, van Paassen P, Navis G, de Zeeuw D, de Jong P E
Groningen Institute for Drug Studies (GIDS), Department of Nephology, University Hospital, The Netherlands.
Nephrol Dial Transplant. 1997;12 Suppl 2:53-6.
In glomerular disease proteinuria usually has a circadian pattern with maximum excretion during the day. Blockade of the renin-angiotensin system (RAS) results in a 50% reduction of proteinuria as measured in 24-h urine collections. We questioned whether anti-proteinuric treatment by blockade of the RAS is as effective during the day as during the night.
We analysed data from two intervention studies on proteinuria in patients with non-diabetic renal disease. In the first study, six hospitalized patients (proteinuria 5.8 +/- 2.9 g/day) were treated with the renin-inhibitor remikiren 600 mg o.d. during 8 days. In the second study eight ambulant patients (proteinuria 7.5 +/- 2.7 g/day) were treated during 6 weeks with the ACE-inhibitor trandolapril 4 mg o.d. Urine was collected in a day- and in a night-time portion.
Daytime proteinuria declined from 0.29 +/- 0.15 to 0.22 +/- 0.11 g/h (P < 0.05) during remikiren and from 0.33 +/- 0.14 to 0.16 +/- 0.08 g/h (P < 0.05) during trandolapril. Night-time proteinuria, however, was not significantly reduced from 0.23 +/- 0.11 to 0.19 +/- 0.11 g/h during remikiren and from 0.29 +/- 0.17 to 0.20 +/- 0.12 g/h during trandolapril. Both interventions effectively lowered blood pressure during the day as well as the night.
In both studies relative nocturnal therapy resistance to the antiproteinuric effect of RAS blockade was found, despite 24-h efficacy of blood pressure effect. This may have clinical relevance because it contributes to rest-proteinuria and thus may affect long term renal function outcome. It may be worthwhile to explore alternative therapeutic regimens to improve the nocturnal antiproteinuric response.
在肾小球疾病中，蛋白尿通常具有昼夜节律模式，白天排泄量最大。肾素 - 血管紧张素系统（RAS）的阻断可使24小时尿蛋白排泄量减少50%。我们质疑通过阻断RAS进行的抗蛋白尿治疗在白天是否与夜间一样有效。
我们分析了两项关于非糖尿病肾病患者蛋白尿的干预研究数据。在第一项研究中，6名住院患者（蛋白尿5.8±2.9 g/天）接受了肾素抑制剂瑞米吉仑600 mg每日一次，持续8天的治疗。在第二项研究中，8名门诊患者（蛋白尿7.5±2.7 g/天）接受了血管紧张素转换酶抑制剂群多普利4 mg每日一次，持续6周的治疗。尿液分为白天和夜间部分收集。
在使用瑞米吉仑期间，白天蛋白尿从0.29±0.15降至0.22±0.11 g/小时（P<0.05），在使用群多普利期间，从0.33±0.14降至0.16±0.08 g/小时（P<0.05）。然而，在使用瑞米吉仑期间，夜间蛋白尿从0.23±0.11降至0.19±0.11 g/小时，在使用群多普利期间，从0.29±0.17降至0.20±0.12 g/小时，均无显著降低。两种干预措施在白天和夜间均有效降低了血压。
在两项研究中，尽管RAS阻断对血压的作用在24小时内有效，但均发现夜间对RAS阻断抗蛋白尿作用存在相对治疗抵抗。这可能具有临床相关性，因为它导致静息蛋白尿，从而可能影响长期肾功能结局。探索替代治疗方案以改善夜间抗蛋白尿反应可能是值得的。
